nach oben

Cancer and Metastasis Reviews

Erschienen in:

01.03.2015 | Clinical

Low immunogenicity in non-small cell lung cancer; do new developments and novel treatments have a role?

verfasst von: R. E. Gardiner, S. Jahangeer, P. Forde, A. B. Ariffin, B. Bird, D. Soden, J. Hinchion

Erschienen in: Cancer and Metastasis Reviews | Ausgabe 1/2015

Einloggen, um Zugang zu erhalten

Abstract

Approximately 1.6 million new cases of lung cancer are diagnosed annually (Jemal et al. CA: A Cancer Journal for Clinicians, 61, 69–90, 2011) and it remains the leading cause of cancer-related mortality worldwide. Despite decades of bench and clinical research to attempt to improve outcome for locally advanced, good performance status patients, the 5-year survival remains less than 15 % (Molina et al. 2008). Immune checkpoint inhibitor (ICH) therapies have shown a significant promise in preclinical and clinical trails to date in the treatment of non-small cell lung cancer (NSCLC). The idea of combining these systemic immune therapies with local ablative techniques is one that is gaining momentum. Electrochemotherapy (ECT) is a unique atraumatic local therapy that has had very promising objective response rates and a number of advantages including but not limited to its immunostimulatory effects. ECT in combination with ICHs offers a novel approach for dealing with this difficult disease process.

Henley, S. J., Richards, T. B., Underwood, J. M., Eheman, C. R., Plescia, M., & McAfee, T. A. (2014). Lung cancer incidence trends among men and women—United States, 2005–2009. MMWR. Morbidity and Mortality Weekly Report, 63(1), 1–5.PubMed

D’addario, G., Früh, M., Reck, M., Baumann, P., Klepetko, W., & Felip, E. (2010). Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology, 21(suppl 5), v116–v119.PubMedCrossRef

Little, A. G., Rusch, V. W., Bonner, J. A., Gaspar, L. E., Green, M. R., Webb, W. R., et al. (2005). Patterns of surgical care of lung cancer patients. The Annals of Thoracic Surgery, 80(6), 2051–2056.PubMedCrossRef

Crino, L., Weder, W., Van Meerbeeck, J., & Felip, E. (2010). Early stage and locally advanced (non-metastatic) non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology, 21(suppl 5), v103–v115.PubMedCrossRef

Schiller, J. H., Harrington, D., Belani, C. P., Langer, C., Sandler, A., Krook, J., et al. (2002). Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. New England Journal of Medicine, 346(2), 92–98.PubMedCrossRef

Scagliotti, G. V., Parikh, P., von Pawel, J., Biesma, B., Vansteenkiste, J., Manegold, C., et al. (2008). Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. Journal of Clinical Oncology, 26(21), 3543–3551.PubMedCrossRef

Delbaldo, C., Michiels, S., Syz, N., Soria, J.-C., Le Chevalier, T., & Pignon, J.-P. (2004). Benefits of adding a drug to a single-agent or a 2-agent chemotherapy regimen in advanced non-small-cell lung cancer: a meta-analysis. JAMA, 292(4), 470–484.PubMedCrossRef

Shaw, A. T., Kim, D.-W., Mehra, R., Tan, D. S., Felip, E., Chow, L. Q., et al. (2014). Ceritinib in ALK-rearranged non-small-cell lung cancer. New England Journal of Medicine, 370(13), 1189–1197.PubMedPubMedCentralCrossRef

Zhou, C., Wu, Y.-L., Chen, G., Feng, J., Liu, X.-Q., Wang, C., et al. (2011). Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. The Lancet Oncology, 12(8), 735–742.PubMedCrossRef

10.

Forde, P. M., Kelly, R. J., & Brahmer, J. R. (2014). New strategies in lung cancer: translating immunotherapy into clinical practice. Clinical Cancer Research, 20(5), 1067–1073.PubMedCrossRef

11.

Swann, J. B., & Smyth, M. J. (2007). Immune surveillance of tumors. Journal of Clinical Investigation, 117, 137–1146.CrossRef

12.

Zitvogel, L., Tesniere, A., & Kroemer, G. (2006). Cancer despite immunosurveillance: immunoselection and immunosubversion. Nature Reviews Immunology, 6, 715–727.PubMedCrossRef

13.

Langman, R., & Cohn, M. (2000). A minimal model for the self-nonself discrimination: a return to the basics. In Seminars in immunology (vol. 12, pp. 189–195, vol. 3). Elsevier.

14.

Burnet, F., & Fenner, F. (1949). The production of antibodies. Monograph of the Walter and Eliza Hall Institute, Melbourne. The production of antibodies. Monograph of the Walter and Eliza Hall Institute, Melbourne (2 edn).

15.

Pradeu, T., & Carosella, E. D. (2006). On the definition of a criterion of immunogenicity. Proceedings of the National Academy of Sciences, 103(47), 17858–17861.CrossRef

16.

Segal, N. H., Parsons, D. W., Peggs, K. S., Velculescu, V., Kinzler, K. W., Vogelstein, B., et al. (2008). Epitope landscape in breast and colorectal cancer. Cancer Research, 68(3), 889–892.PubMedCrossRef

17.

Shankaran, V., Ikeda, H., Bruce, A. T., White, J. M., Swanson, P. E., Old, L. J., et al. (2001). IFNγ and lymphocytes prevent primary tumour development and shape tumour immunogenicity. Nature, 410(6832), 1107–1111.PubMedCrossRef

18.

Smyth, M. J., Dunn, G. P., & Schreiber, R. D. (2006). Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Advances in Immunology, 90, 1–50.PubMedCrossRef

19.

Vesely, M. D., Kershaw, M. H., Schreiber, R. D., & Smyth, M. J. (2011). Natural innate and adaptive immunity to cancer. Annual Review of Immunology, 29, 235–271.PubMedCrossRef

20.

Einhorn, L., Bond, W., Hornback, N., & Joe, B. (1978). Long-term results in combined-modality treatment of small cell carcinoma of the lung. In Seminars in oncology (vol. 5, pp. 309–313, vol. 3).

21.

Schiller, J. H., Morgan-Ihrig, C., & Levitt, M. L. (1995). Concomitant administration of interleukin-2 plus tumor necrosis factor in advanced non-small cell lung cancer. American Journal of Clinical Oncology, 18(1), 47–51.PubMedCrossRef

22.

Jansen, R. L., Slingerland, R., Goey, S. H., Franks, C. R., Bolhuis, R. L., & Stoter, G. (1992). Interleukin-2 and interferon-[alpha] in the treatment of patients with advanced non-small-cell lung cancer. Journal of Immunotherapy, 12(1), 70–73.PubMedCrossRef

23.

Chatterjee, S., Crozet, L., Damotte, D., Iribarren, K., Schramm, C., Alifano, M., et al. (2014). TLR7 promotes tumor progression, chemotherapy resistance, and poor clinical outcomes in non-small cell lung cancer. Cancer Research, 74(18), 5008–5018.PubMedCrossRef

24.

Ligers, A., Xu, C., Saarinen, S., Hillert, J., & Olerup, O. (1999). The CTLA-4 gene is associated with multiple sclerosis. Journal of Neuroimmunology, 97(1), 182–190.PubMedCrossRef

25.

Yanagawa, T., Hidaka, Y., Guimaraes, V., Soliman, M., & DeGroot, L. (1995). CTLA-4 gene polymorphism associated with Graves’ disease in a Caucasian population. The Journal of Clinical Endocrinology & Metabolism, 80(1), 41–45.

26.

Van der Auwera, B., Vandewalle, C., Schuit, F., Winnock, F., De Leeuw, I., Van Imschoot, S., et al. (1997). CTLA-4 gene polymorphism confers susceptibility to insulin-dependent diabetes mellitus (IDDM) independently from age and from other genetic or immune disease markers. Clinical & Experimental Immunology, 110(1), 98–103.CrossRef

27.

Nishimura, H., Okazaki, T., Tanaka, Y., Nakatani, K., Hara, M., Matsumori, A., et al. (2001). Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science, 291(5502), 319–322.PubMedCrossRef

28.

Ansari, M. J. I., Salama, A. D., Chitnis, T., Smith, R. N., Yagita, H., Akiba, H., et al. (2003). The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice. The Journal of Experimental Medicine, 198(1), 63–69.PubMedPubMedCentralCrossRef

29.

Chambers, C. A., Kuhns, M. S., Egen, J. G., & Allison, J. P. (2001). CTLA-4-mediated inhibition in regulation of T cell responses: mechanisms and manipulation in tumor immunotherapy. Annual Review of Immunology, 19(1), 565–594.PubMedCrossRef

30.

Brahmer, J., Horn, L., Antonia, S., Spigel, D., Gandhi, L., Sequist, L., et al. (2013). Survival and long-term follow-up of the phase I trial of nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients (pts) with previously treated advanced non-small cell lung cancer (NSCLC). Journal of Clinical Oncology, 31(suppl), abstract 8030.

31.

Purdy, A. K., & Campbell, K. S. (2009). Natural killer cells and cancer: regulation by the killer cell Ig-like receptors (KIR). Cancer Biology & Therapy, 8(23), 2209–2218.CrossRef

32.

Zhang, B. (2010). CD73: a novel target for cancer immunotherapy. Cancer Research, 70(16), 6407–6411.PubMedPubMedCentralCrossRef

33.

Ngiow, S. F., von Scheidt, B., Akiba, H., Yagita, H., Teng, M. W., & Smyth, M. J. (2011). Anti-TIM3 antibody promotes T cell IFN-γ-mediated antitumor immunity and suppresses established tumors. Cancer Research, 71(10), 3540–3551.PubMedCrossRef

34.

Woo, S.-R., Turnis, M. E., Goldberg, M. V., Bankoti, J., Selby, M., Nirschl, C. J., et al. (2012). Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Research, 72(4), 917–927.PubMedPubMedCentralCrossRef

35.

Watanabe, N., Gavrieli, M., Sedy, J. R., Yang, J., Fallarino, F., Loftin, S. K., et al. (2003). BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1. Nature Immunology, 4(7), 670–679.PubMedCrossRef

36.

Teft, W. A., Kirchhof, M. G., & Madrenas, J. (2006). A molecular perspective of CTLA-4 function. Annual Review of Immunology, 24, 65–97.PubMedCrossRef

37.

Wolchok, J. D., & Saenger, Y. (2008). The mechanism of anti-CTLA- 4 activity and the negative regulation of T-cell activation. The Oncologist, 13(Suppl 4), 2–9.PubMedCrossRef

38.

Selby, M., Engelhardt, J., Quigley, M., et al. (2013). Anti-CTLA-4 antibodies of IgG2a isotype enhance antitumor activity through reduction of intratumoral regulatory T cells. Cancer Immunology Research, 1(1), 32–42. 1(1), 32–42.PubMedCrossRef

39.

Sakaguchi, S., Yamaguchi, T., Nomura, T., & Ono, M. (2008). Regulatory T cells and immune tolerance. Cell, 133(5), 775–787.PubMedCrossRef

40.

Peggs, K. S., Quezada, S. A., Chambers, C. A., Korman, A. J., & Allison, J. P. (2009). Blockade of CTLA-4 on both effector and regulatory T cell compartments contributes to the antitumor activity of anti-CTLA-4 antibodies. The Journal of Experimental Medicine, 206(8), 1717–1725.PubMedPubMedCentralCrossRef

41.

Salvi, S., Fontana, V., Boccardo, S., Merlo, D. F., Margallo, E., Laurent, S., et al. (2012). Evaluation of CTLA-4 expression and relevance as a novel prognostic factor in patients with non-small cell lung cancer. Cancer Immunology, Immunotherapy, 61(9), 1463–1472.PubMedCrossRef

42.

Sundar, R., Soong, R., Cho, B.-C., Brahmer, J.R., & Soo, R.A. (2014). Immunotherapy in the treatment of non-small cell lung cancer. Lung Cancer, 85(2), 101–109.

43.

Phan, G. Q., Yang, J. C., Sherry, R. M., et al. (2003). Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proceedings of the National Academy of Sciences of the United States of America, 100, 8372–8377.PubMedPubMedCentralCrossRef

44.

Robert, C., Thomas, L., Bondarenko, I., O’Day, S., Weber, J., Garbe, C., et al. (2011). Ipilimumab plus dacarbazine for previously untreated metastatic melanoma. New England Journal of Medicine, 364(26), 2517–2526.PubMedCrossRef

45.

Hodi, F. S., O’Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., et al. (2010). Improved survival with ipilimumab in patients with metastatic melanoma. New England Journal of Medicine, 363(8), 711–723.PubMedPubMedCentralCrossRef

46.

Small, E., Higano, C., Tchekmedyian, N., Sartor, O., Stein, B., Young, R., et al. (2006). Randomized phase II study comparing 4 monthly doses of ipilimumab (MDX-010) as a single agent or in combination with a single dose of docetaxel in patients with hormone-refractory prostate cancer. Journal of Clinical Oncology, 24(suppl 18), 4609.

47.

Hodi, F. S., Mihm, M. C., Soiffer, R. J., Haluska, F. G., Butler, M., Seiden, M. V., et al. (2003). Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proceedings of the National Academy of Sciences, 100(8), 4712–4717.CrossRef

48.

Waterhouse, P., Penninger, J. M., Timms, E., Wakeham, A., Shahinian, A., Lee, K. P., et al. (1995). Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science, 270(5238), 985–988.PubMedCrossRef

49.

Weber, J. S., Dummer, R., de Pril, V., Lebbé, C., & Hodi, F. S. (2013). Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab. Cancer, 119(9), 1675–1682.PubMedCrossRef

50.

Franzen, D., Schad, K., Dummer, R., & Russi, E. W. (2013). Severe acute respiratory distress syndrome due to ipilimumab. European Respiratory Journal, 42(3), 866–868.PubMedCrossRef

51.

Di Giacomo, A.M., Biagioli, M., & Maio, M. (2010). The emerging toxicity profiles of anti-CTLA-4 antibodies across clinical indications. In Seminars in oncology (vol. 37, pp. 499–507, vol. 5). Elsevier.

52.

Pintova, S., Sidhu, H., Friedlander, P. A., & Holcombe, R. F. (2013). Sweet’s syndrome in a patient with metastatic melanoma after ipilimumab therapy. Melanoma Research, 23(6), 498–501.PubMedCrossRef

53.

Juszczak, A., Gupta, A., Karavitaki, N., Middleton, M. R., & Grossman, A. B. (2012). Mechanisms in endocrinology: ipilimumab: a novel immunomodulating therapy causing autoimmune hypophysitis: a case report and review. European Journal of Endocrinology, 167(1), 1–5.PubMedCrossRef

54.

Chow, L. (2012). Exploring novel immune-related toxicities and endpoints with immune-checkpoint inhibitors in non-small cell lung cancer. In American Society of Clinical Oncology educational book/ASCO. American Society of Clinical Oncology. Meeting (vol. 2013, pp. 280–285).

55.

Weber, J., Thompson, J. A., Hamid, O., Minor, D., Amin, A., Ron, I., et al. (2009). A randomized, double-blind, placebo-controlled, phase II study comparing the tolerability and efficacy of ipilimumab administered with or without prophylactic budesonide in patients with unresectable stage III or IV melanoma. Clinical Cancer Research, 15(17), 5591–5598.PubMedCrossRef

56.

O’Day, S., Maio, M., Chiarion-Sileni, V., Gajewski, T., Pehamberger, H., Bondarenko, I., et al. (2010). Efficacy and safety of ipilimumab monotherapy in patients with pretreated advanced melanoma: a multicenter single-arm phase II study. Annals of Oncology, 21(8), 1712–1717.PubMedCrossRef

57.

Zatloukal, P., Heo, D., Park, K., Kang, J., Butts, C., Bradford, D., et al. (2009). Randomized phase II clinical trial comparing tremelimumab (CP-675,206) with best supportive care (BSC) following first-line platinum-based therapy in patients (pts) with advanced nonsmall cell lung cancer (NSCLC). Journal of Clinical Oncology, 27, 8071.

58.

Correale, P., Del Vecchio, M. T., La Placa, M., Montagnani, F., Di Genova, G., Savellini, G. G., et al. (2008). Chemotherapeutic drugs may be used to enhance the killing efficacy of human tumor antigen peptide-specific CTLs. Journal of Immunotherapy, 31(2), 132–147.PubMedCrossRef

59.

Masters, G., Barreto, L., Girit, E., & Jure-Kunkel, M. (2009). Antitumor activity of cytotoxic T-lymphocyte antigen-4 blockade alone or combined with paclitaxel, etoposide, or gemcitabine in murine models. In Journal of Immunotherapy (vol. 32, pp. 994–994, vol. 9): Lippincott Williams & Wilkins 530 Walnut St, Philadelphia, PA 19106–3621 USA.

60.

Lynch, T. J., Bondarenko, I., Luft, A., Serwatowski, P., Barlesi, F., Chacko, R., et al. (2012). Ipilimumab in combination with paclitaxel and carboplatin as first-line treatment in stage IIIB/IV non–small-cell lung cancer: results from a randomized, double-blind, multicenter phase II study. Journal of Clinical Oncology, 30(17), 2046–2054.PubMedCrossRef

61.

Wolchok, J. D., Hoos, A., O’Day, S., Weber, J. S., Hamid, O., Lebbé, C., et al. (2009). Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria. Clinical Cancer Research, 15(23), 7412–7420.PubMedCrossRef

62.

Hoos, A., Eggermont, A.M., Janetzki, S., Hodi, F.S., Ibrahim, R., Anderson, A., et al. (2010). Improved endpoints for cancer immunotherapy trials. Journal of the National Cancer Institute, 102:1388–1397.

63.

Eisenhauer, E., Therasse, P., Bogaerts, J., Schwartz, L., Sargent, D., Ford, R., et al. (2009). New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). European Journal of Cancer, 45(2), 228–247.PubMedCrossRef

64.

Mellman, I., Coukos, G., & Dranoff, G. (2011). Cancer immunotherapy comes of age. Nature, 480(7378), 480–489.PubMedPubMedCentralCrossRef

65.

Pennock, G. K., Waterfield, W., & Wolchok, J. D. (2012). Patient responses to ipilimumab, a novel immunopotentiator for metastatic melanoma: how different are these from conventional treatment responses? American Journal of Clinical Oncology, 35(6), 606–611.PubMedCrossRef

66.

Nishino, M., Jagannathan, J. P., Ramaiya, N. H., & Van den Abbeele, A. D. (2010). Revised RECIST guideline version 1.1: what oncologists want to know and what radiologists need to know. American Journal of Roentgenology, 195(2), 281–289.PubMedCrossRef

67.

Squibb, B.-M. (2000). Trial in squamous non small cell lung cancer subjects comparing ipilimumab plus paclitaxel and carboplatin versus placebo plus paclitaxel and carboplatin ClinicalTrials.gov identifier: NCT01285609. National Library of Medicine (US), Clinical-Trials. gov, Bethesda.

68.

Squibb, B.-M. Phase 3 trial in squamous non small cell lung cancer subjects comparing ipilimumab plus paclitaxel and carboplatin versus placebo plus paclitaxel and carboplatin. ClinicalTrials.gov Identifier: NCT02279732.

69.

Topalian, S. L., Drake, C. G., & Pardoll, D. M. (2012). Targeting the PD-1/B7-H1 (PD-L1) pathway to activate anti-tumor immunity. Current Opinion in Immunology, 24(2), 207–212.PubMedPubMedCentralCrossRef

70.

Gabrilovich, D. (2004). Mechanisms and functional significance of tumour-induced dendritic-cell defects. Nature Reviews Immunology, 4(12), 941–952.PubMedCrossRef

71.

Dong, H., Strome, S. E., Salomao, D. R., Tamura, H., Hirano, F., Flies, D. B., et al. (2002). Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nature Medicine, 8(8), 793–800.PubMed

72.

Freeman, G. J., Long, A. J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., et al. (2000). Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. The Journal of Experimental Medicine, 192(7), 1027–1034.PubMedPubMedCentralCrossRef

73.

Park, J.-J., Omiya, R., Matsumura, Y., Sakoda, Y., Kuramasu, A., Augustine, M. M., et al. (2010). B7-H1/CD80 interaction is required for the induction and maintenance of peripheral T-cell tolerance. Blood, 116(8), 1291–1298.PubMedPubMedCentralCrossRef

74.

Blank, C., Kuball, J., Voelkl, S., Wiendl, H., Becker, B., Walter, B., et al. (2006). Blockade of PD-L1 (B7-H1) augments human tumor-specific T cell responses in vitro. International Journal of Cancer, 119(2), 317–327.PubMedCrossRef

75.

Iwai, Y., Ishida, M., Tanaka, Y., Okazaki, T., Honjo, T., & Minato, N. (2002). Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proceedings of the National Academy of Sciences, 99(19), 12293–12297.CrossRef

76.

Topalian, S. L., Hodi, F. S., Brahmer, J. R., Gettinger, S. N., Smith, D. C., McDermott, D. F., et al. (2012). Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. New England Journal of Medicine, 366(26), 2443–2454.PubMedPubMedCentralCrossRef

77.

Brahmer, J. R., Tykodi, S. S., Chow, L. Q., Hwu, W.-J., Topalian, S. L., Hwu, P., et al. (2012). Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. New England Journal of Medicine, 366(26), 2455–2465.PubMedPubMedCentralCrossRef

78.

Hamid, O., Robert, C., Daud, A., Hodi, F. S., Hwu, W.-J., Kefford, R., et al. (2013). Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. New England Journal of Medicine, 369(2), 134–144.PubMedPubMedCentralCrossRef

79.

Nishimura, H., Nose, M., Hiai, H., Minato, N., & Honjo, T. (1999). Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity, 11(2), 141–151.PubMedCrossRef

80.

Topalian, S., Sznol, M., Brahmer, J., McDermott, D., Smith, D., Gettinger, S., et al. (2013). Nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients with advanced solid tumors: Survival and long-term safety in a phase I trial. Journal of Clinical Oncology, 31, S3002.

81.

Brahmer, J. R., Drake, C. G., Wollner, I., Powderly, J. D., Picus, J., Sharfman, W. H., et al. (2010). Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. Journal of Clinical Oncology, 28(19), 3167–3175.PubMedPubMedCentralCrossRef

82.

Brahmer, J., Horn, L., Antonia, S., Spigel, D., Gandhi, L., & Sequist, L. (2013). Nivolumab (anti-PD-1; BMS-936558; ONO-4538) in patients with non-small cell lung cancer (NSCLC): overall survival and long-term safety in a phase 1 trial. IASLC 15th World Conference on Lung Cancer. 2013. Abstract MO18.03, 3, 27–30.

83.

Squibb, B.-M. Study of BMS-936558 (Nivolumab) compared to docetaxel in previously treated advanced or metastatic squamous cell non-small cell lung cancer (NSCLC) (CheckMate 017) ClinicalTrials.gov Identifier: NCT01642004.

84.

Squibb, B.-M. Study of nivolumab (BMS-936558) in combination with gemcitabine/cisplatin, pemetrexed/cisplatin, carboplatin/paclitaxel, bevacizumab maintenance, erlotinib, ipilimumab or as monotherapy in subjects with stage IIIB/IV non-small cell lung cancer (NSCLC) (CheckMate 012) ClinicalTrials.gov Identifier: NCT01454102.

85.

Rizvi, N., Antonia, S., Chow, L., Brahmer, J., Juergens, R., & Borghaei, H. (2013). A phase I study of nivolumab (anti-PD-1; BMS-936558, ONO-4538) plus platinum-based doublet chemotherapy (PT-doublet) in chemotherapy-naive non-small cell lung cancer (NSCLC) patients (pts). Journal of Clinical Oncology, 31, abstract 8072.

86.

Squibb, B.-M. Study of BMS-936558 (nivolumab) compared to docetaxel in previously treated metastatic non-squamous NSCLC (CheckMate 057) ClinicalTrials.gov Identifier: NCT01673867.

87.

Garon, E., Gandhi, L., Rizvi, N., Hui, R., Balmanoukian, A., Patnaik, A., et al. (2014). LBA43 antitumor activity of pembrolizumab (pembro; MK-3475) and correlation with programmed death ligand 1 (PD-L1) expression in a pooled analysis of patients (PTS) with advanced non-small cell lung carcinoma (NSCLC). Annals of Oncology, 25(suppl 4), mdu438. 451.

88.

Corp., M. S. D. Study of MK-3475 (pembrolizumab) versus platinum-based chemotherapy for participants with PD-L1-positive advanced or metastatic non-small cell lung cancer (MK-3475–042/KEYNOTE-042) ClinicalTrials.gov Identifier: NCT02220894.

89.

Corp, M. S. D. Study of pembrolizumab (MK-3475) compared to platinum-based chemotherapies in participants with metastatic non-small cell lung cancer (MK-3475–024/KEYNOTE-024) ClinicalTrials.gov Identifier: NCT02142738.

90.

Corp., M. S. D. Study of two doses of MK-3475 (pembrolizumab) versus docetaxel in previously-treated participants with non-small cell lung cancer (MK-3475–010/KEYNOTE-010) ClinicalTrials.gov Identifier: NCT01905657.

91.

Corp., M. S. D. Study of pembrolizumab (MK-3475) monotherapy in participants with advanced solid tumors and pembrolizumab combination therapy in participants with advanced non-small cell lung cancer (MK-3475–011/KEYNOTE-011) ClinicalTrials.gov Identifier: NCT01840579.

92.

Yang, C.-Y., Lin, M.-W., Chang, Y.-L., Wu, C.-T., & Yang, P.-C. (2014). Programmed cell death-ligand 1 expression in surgically resected stage I pulmonary adenocarcinoma and its correlation with driver mutations and clinical outcomes. European Journal of Cancer, 50(7), 1361–1369.PubMedCrossRef

93.

Velcheti, V., Schalper, K. A., Carvajal, D. E., Anagnostou, V. K., Syrigos, K. N., Sznol, M., et al. (2013). Programmed death ligand-1 expression in non-small cell lung cancer. Laboratory Investigation, 94(1), 107–116.PubMedCrossRef

94.

Mu, C.-Y., Huang, J.-A., Chen, Y., Chen, C., & Zhang, X.-G. (2011). High expression of PD-L1 in lung cancer may contribute to poor prognosis and tumor cells immune escape through suppressing tumor infiltrating dendritic cells maturation. Medical Oncology, 28(3), 682–688.PubMedCrossRef

95.

Sica, G. L., Choi, I.-H., Zhu, G., Tamada, K., Wang, S.-D., Tamura, H., et al. (2003). B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity, 18(6), 849–861.PubMedCrossRef

96.

Brahmer, J. R., & Pardoll, D. M. (2013). Immune checkpoint inhibitors: making immunotherapy a reality for the treatment of lung cancer. Cancer Immunology Research, 1(2), 85–91.PubMedPubMedCentralCrossRef

97.

Konishi, J., Yamazaki, K., Azuma, M., Kinoshita, I., Dosaka-Akita, H., & Nishimura, M. (2004). B7-H1 expression on non-small cell lung cancer cells and its relationship with tumor-infiltrating lymphocytes and their PD-1 expression. Clinical Cancer Research, 10(15), 5094–5100.PubMedCrossRef

98.

Chen, Y.-Y., Wang, L.-B., Zhu, H.-L., Li, X.-Y., Zhu, Y.-P., Yin, Y.-L., et al. (2013). Relationship between programmed death-ligand 1 and clinicopathological characteristics in non-small cell lung cancer patients. Chinese Medical Sciences Journal, 28(3), 147–151.PubMedCrossRef

99.

Grosso, J., Horak, C., Inzunza, D., Cardona, D., Simon, J., Gupta, A., et al. (2013). Association of tumor PD-L1 expression and immune biomarkers with clinical activity in patients (pts) with advanced solid tumors treated with nivolumab (anti-PD-1; BMS-936558; ONO-4538). Journal of Clinical Oncology, 31(Suppl), 3016.

100.

Spigel, D.R., Gettinger, S.N., Horn, L., Herbst, R.S., Gandhi, L., Gordon, M., et al. (2013). Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). Journal of Clinical Oncology, 31(suppl), abstract 8008.

101.

Horn, L., Herbst, R., Spigel, D., Gettinger, S., Gordon, M., & Hollebecque, A. (2013). An analysis of the relationship of clinical activity to baseline EGFR status, PD-L1 expression and prior treatment history in patients with non-small cell lung cancer (NSCLC) following PD-L1 blockade with MPDL3280A (anti-PDL1). Abstract MO18, 1, 27–30.

102.

Genentech, I. A phase 1b study of MPDL3280A (an engineered anti-PDL1 antibody) in combination with avastin (bevacizumab) and/or with chemotherapy in patients with locally advanced or metastatic solid tumors ClinicalTrials.gov Identifier: NCT01633970.

103.

Genentech, I. A phase 2 study of MPDL3280A (an engineered anti-PDL1 antibody) in patients with PD-L1 positive locally advanced or metastatic non-small cell lung cancer - “FIR” ClinicalTrials.gov Identifier: NCT01846416.

104.

Roche, H.-L. A randomized phase 2 study of MPDL3280A (an engineered anti-PDL1 antibody) compared with docetaxel in patients with locally advanced or metastatic non-small cell lung cancer who have failed platinum therapy - “POPLAR” ClinicalTrials.gov Identifier: NCT01903993.

105.

Roche, H.-L. A randomized phase 3 study of MPDL3280A (an engineered anti-PDL1 antibody) compared to docetaxel in patients with locally advanced or metastatic non-small cell lung cancer who have failed platinum therapy - “OAK” ClinicalTrials.gov Identifier: NCT02008227.

106.

Khleif, S., Lutzky, J., Segal, N., Antonia, S., Blake-Haskins, A., Stewart, R., et al. (2013). MEDI4736, an anti-PD-L1 antibody with modified Fc domain: preclinical evaluation and early clinical results from a phase 1 study in patients with advanced solid tumors. In European Journal of Cancer (vol. 49, pp. S161): Elsevier Sci Ltd The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, Oxon, England

107.

Heinrich, P., Behrmann, I., Haan, S., Hermanns, H., Muller-Newen, G., & Schaper, F. (2003). Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochemical Journal, 374, 1–20.PubMedPubMedCentralCrossRef

108.

Flynn, J. C. (2014). Opportunistic autoimmune disorders potentiated by immune-checkpoint inhibitors anti-CTLA-4 and anti-PD-1. Frontiers in Immunology, 5, 1–7.

109.

Curran, M. A., Montalvo, W., Yagita, H., & Allison, J. P. (2010). PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proceedings of the National Academy of Sciences, 107(9), 4275–4280.CrossRef

110.

Selby, M., Engelhardt, J., Lu, L., Quigley, M., Wang, C., Chen, B., et al. (2013). Antitumor activity of concurrent blockade of immune checkpoint molecules CTLA-4 and PD-1 in preclinical models. Journal of Clinical Oncology, 31(suppl), abstract 3061.

111.

Wolchok, J. D., Kluger, H., Callahan, M. K., Postow, M. A., Rizvi, N. A., Lesokhin, A. M., et al. (2013). Nivolumab plus ipilimumab in advanced melanoma. New England Journal of Medicine, 369(2), 122–133.PubMedCrossRef

112.

Zhou, P., Liang, P., Dong, B., Yu, X., Han, Z., & Xu, Y. (2011). Phase I clinical study of combination therapy with microwave ablation and cellular immunotherapy in hepatocellular carcinoma. Cancer Biology & Therapy, 11(5), 450–456.CrossRef

113.

Yuanying, Y., Lizhi, N., Feng, M., Xiaohua, W., Jianying, Z., Fei, Y., et al. (2013). Therapeutic outcomes of combining cryotherapy, chemotherapy and DC-CIK immunotherapy in the treatment of metastatic non-small cell lung cancer. Cryobiology, 67(2), 235–240.PubMedCrossRef

114.

Cui, J., Wang, N., Zhao, H., Jin, H., Wang, G., Niu, C., et al. (2014). Combination of radiofrequency ablation and sequential cellular immunotherapy improves progression-free survival for patients with hepatocellular carcinoma. International Journal of Cancer, 134(2), 342–351.PubMedCrossRef

115.

Niu, L.-Z., Li, J.-L., Zeng, J.-Y., Mu, F., Liao, M.-T., Yao, F., et al. (2013). Combination treatment with comprehensive cryoablation and immunotherapy in metastatic hepatocellular cancer. World Journal of Gastroenterology: WJG, 19(22), 3473.PubMedPubMedCentralCrossRef

116.

Nikfarjam, M., Muralidharan, V., & Christophi, C. (2005). Mechanisms of focal heat destruction of liver tumors. Journal of Surgical Research, 127(2), 208–223.PubMedCrossRef

117.

Pennathur, A., Abbas, G., Gooding, W. E., Schuchert, M. J., Gilbert, S., Christie, N. A., et al. (2009). Image-guided radiofrequency ablation of lung neoplasm in 100 consecutive patients by a thoracic surgical service. The Annals of Thoracic Surgery, 88(5), 1601–1608.PubMedPubMedCentralCrossRef

118.

Lanuti, M., Sharma, A., Willers, H., Digumarthy, S. R., Mathisen, D. J., & Shepard, J.-A. O. (2012). Radiofrequency ablation for stage I non-small cell lung cancer: management of locoregional recurrence. The Annals of Thoracic Surgery, 93(3), 921–928.PubMedCrossRef

119.

Zhu, J. C., Yan, T. D., & Morris, D. L. (2008). A systematic review of radiofrequency ablation for lung tumors. Annals of Surgical Oncology, 15(6), 1765–1774.PubMedCrossRef

120.

Simon, C. J., Dupuy, D. E., DiPetrillo, T. A., Safran, H. P., Grieco, C. A., Ng, T., et al. (2007). Pulmonary radiofrequency ablation: long-term safety and efficacy in 153 patients 1. Radiology, 243(1), 268–275.PubMedCrossRef

121.

Lanuti, M., Sharma, A., Digumarthy, S. R., Wright, C. D., Donahue, D. M., Wain, J. C., et al. (2009). Radiofrequency ablation for treatment of medically inoperable stage I non-small cell lung cancer. The Journal of Thoracic and Cardiovascular Surgery, 137(1), 160–166.PubMedCrossRef

122.

Hiraki, T., Sakurai, J., Tsuda, T., Gobara, H., Sano, Y., Mukai, T., et al. (2006). Risk factors for local progression after percutaneous radiofrequency ablation of lung tumors. Cancer, 107(12), 2873–2880.PubMedCrossRef

123.

Hiraki, T., Gobara, H., Mimura, H., Toyooka, S., Fujiwara, H., Yasui, K., et al. (2011). Radiofrequency ablation of lung cancer at Okayama University Hospital: a review of 10 years of experience. Acta Medica Okayama, 65(5), 287–297.PubMed

124.

Ambrogi, M. C., Lucchi, M., Dini, P., Melfi, F., Fontanini, G., Faviana, P., et al. (2006). Percutaneous radiofrequency ablation of lung tumours: results in the mid-term. European Journal of Cardio-Thoracic Surgery, 30(1), 177–183.PubMedCrossRef

125.

Wright, A. S., Lee, F. T., Jr., & Mahvi, D. M. (2003). Hepatic microwave ablation with multiple antennae results in synergistically larger zones of coagulation necrosis. Annals of Surgical Oncology, 10(3), 275–283.PubMedCrossRef

126.

He, W., Hu, X.-D., Wu, D.-F., Guo, L., Zhang, L.-Z., Xiang, D.-Y., et al. (2006). Ultrasonography-guided percutaneous microwave ablation of peripheral lung cancer. Clinical Imaging, 30(4), 234–241.PubMedCrossRef

127.

Wolf, F. J., Grand, D. J., Machan, J. T., DiPetrillo, T. A., Mayo-Smith, W. W., & Dupuy, D. E. (2008). Microwave ablation of lung malignancies: effectiveness, CT findings, and safety in 50 patients 1. Radiology, 247(3), 871–879.PubMedCrossRef

128.

McTaggart, R. A., & Dupuy, D. E. (2007). Thermal ablation of lung tumors. Techniques in Vascular and Interventional Radiology, 10(2), 102–113.PubMedCrossRef

129.

Mala, T. (2006). Cryoablation of liver tumours—a review of mechanisms, techniques and clinical outcome. Minimally Invasive Therapy & Allied Technologies, 15(1), 9–17.CrossRef

130.

den Brok, M., Sutmuller, R. P., Nierkens, S., Bennink, E. J., Frielink, C., Toonen, L. W., et al. (2006). Efficient loading of dendritic cells following cryo and radiofrequency ablation in combination with immune modulation induces anti-tumour immunity. British Journal of Cancer, 95(7), 896–905.CrossRef

131.

Mir, L. M., Orlowski, S., Belehradek, J., Jr., & Paoletti, C. (1991). Electrochemotherapy potentiation of antitumour effect of bleomycin by local electric pulses. European Journal of Cancer and Clinical Oncology, 27(1), 68–72.CrossRef

132.

Serša, G., Čemažar, M., & Miklavčič, D. (1995). Antitumor effectiveness of electrochemotherapy with cis-diamminedichloroplatinum (II) in mice. Cancer Research, 55(15), 3450–3455.PubMed

133.

Babiuk, S., Baca-Estrada, M. E., Foldvari, M., Middleton, D. M., Rabussay, D., Widera, G., et al. (2004). Increased gene expression and inflammatory cell infiltration caused by electroporation are both important for improving the efficacy of DNA vaccines. Journal of Biotechnology, 110(1), 1–10.PubMedCrossRef

134.

Marty, M., Sersa, G., Garbay, J. R., Gehl, J., Collins, C. G., Snoj, M., et al. (2006). Electrochemotherapy—an easy, highly effective and safe treatment of cutaneous and subcutaneous metastases: results of ESOPE (European Standard Operating Procedures of Electrochemotherapy) study. European Journal of Cancer Supplements, 4(11), 3–13.CrossRef

135.

Mir, L. M., Belehradek, M., Domenge, C., Orlowski, S., Poddevin, B., Belehradek, J., Jr., et al. (1990). Electrochemotherapy, a new antitumor treatment: first clinical trial. Comptes Rendus de l’Academie des Sciences, Serie III: Sciences de la Vie, 313(13), 613–618.

136.

Sersa, G., Miklavcic, D., Cemazar, M., Rudolf, Z., Pucihar, G., & Snoj, M. (2008). Electrochemotherapy in treatment of tumours. European Journal of Surgical Oncology (EJSO), 34(2), 232–240.CrossRef

137.

Sersa, G. (2006). The state-of-the-art of electrochemotherapy before the ESOPE study; advantages and clinical uses. European Journal of Cancer Supplements, 4(11), 52–59.CrossRef

138.

Kis, E., Oláh, J., Ócsai, H., Baltás, E., Gyulai, R., Kemény, L., et al. (2011). Electrochemotherapy of cutaneous metastases of melanoma—a case series study and systematic review of the evidence. Dermatologic Surgery, 37(6), 816–824.

139.

Sersa, G., Cufer, T., Paulin, S. M., Cemazar, M., & Snoj, M. (2012). Electrochemotherapy of chest wall breast cancer recurrence. Cancer Treatment Reviews, 38(5), 379–386.PubMedCrossRef

140.

Benevento, R., Santoriello, A., Perna, G., & Canonico, S. (2012). Electrochemotherapy of cutaneous metastasis from breast cancer in elderly patients: a preliminary report. BMC Surgery, 12(Suppl 1), S6.PubMedPubMedCentralCrossRef

141.

Jahangeer, S., Forde, P., Soden, D., & Hinchion, J. (2013). Review of current thermal ablation treatment for lung cancer and the potential of electrochemotherapy as a means for treatment of lung tumours. Cancer Treatment Reviews, 39(8), 862–871.PubMedCrossRef

142.

Okino, M., & Mohri, H. (1987). Effects of a high-voltage electrical impulse and an anticancer drug on in vivo growing tumors. Japanese Journal of Cancer Research: Gann, 78(12), 1319–1321.PubMed

143.

Ricke, J., Jürgens, J.H., Deschamps, F., Tselikas, L., Uhde, K., Kosiek, O., De Baere, T. (2015). Irreversible electroporation (IRE) fails to demonstrate efficacy in a prospective multicenter phase II trial on lung malignancies: The ALICE Trial. Cardiovasc Intervent Radiol. doi:10.1007/s00270-014-1049-0.

144.

Edhemovic, I., Gadzijev, E., Brecelj, E., Miklavcic, D., Kos, B., Zupanic, A., et al. (2011). Electrochemotherapy: a new technological approach in treatment of metastases in the liver. Technology in Cancer Research & Treatment, 10(5), 475–485.

145.

Frandsen, S. K., Gissel, H., Hojman, P., Tramm, T., Eriksen, J., & Gehl, J. (2012). Direct therapeutic applications of calcium electroporation to effectively induce tumor necrosis. Cancer Research, 72(6), 1336–1341.PubMedCrossRef

146.

Hospital, H. (2014). Calcium electroporation for the treatment of cutaneous metastases ClinicalTrials.gov Identifier: NCT01941901.

147.

Markelc, B., Sersa, G., & Cemazar, M. (2013). Differential mechanisms associated with vascular disrupting action of electrochemotherapy: intravital microscopy on the level of single normal and tumor blood vessels. PloS One, 8(3), e59557.PubMedPubMedCentralCrossRef

148.

Gehl, J. (2008). Electroporation for drug and gene delivery in the clinic: doctors go electric. In Electroporation Protocols (pp. 351–359). Springer.

149.

Parkins, C., & Chaplin, D. (1999). Tumour blood flow changes induced by application of electric pulses. European Journal of Cancer, 35(4), 672–677.PubMedCrossRef

150.

Gehl, J., & Geertsen, P. (2000). Efficient palliation of haemorrhaging malignant melanoma skin metastases by electrochemotherapy. Melanoma Research, 10(6), 585–589.PubMedCrossRef

151.

Snoj, M., Cemazar, M., Srnovrsnik, T., Kosir, S. P., & Sersa, G. (2009). Limb sparing treatment of bleeding melanoma recurrence by electrochemotherapy. Tumori, 95(3), 398.PubMed

152.

Matthiessen, L. W., Chalmers, R. L., Sainsbury, D. C. G., Veeramani, S., Kessell, G., Humphreys, A. C., et al. (2011). Management of cutaneous metastases using electrochemotherapy. Acta Oncologica, 50(5), 621–629.PubMedPubMedCentralCrossRef

153.

Matthiessen, L. W., Johannesen, H. H., Hendel, H. W., Moss, T., Kamby, C., & Gehl, J. (2012). Electrochemotherapy for large cutaneous recurrence of breast cancer: a phase II clinical trial. Acta Oncologica, 51(6), 713–721.PubMedCrossRef

154.

Campana, L. G., Valpione, S., Falci, C., Mocellin, S., Basso, M., Corti, L., et al. (2012). The activity and safety of electrochemotherapy in persistent chest wall recurrence from breast cancer after mastectomy: a phase-II study. Breast Cancer Research and Treatment, 134(3), 1169–1178.PubMedCrossRef

155.

Larkin, J. O., Collins, C. G., Aarons, S., Tangney, M., Whelan, M., O’Reily, S., et al. (2007). Electrochemotherapy: aspects of preclinical development and early clinical experience. Annals of Surgery, 245(3), 469.PubMedPubMedCentralCrossRef

156.

Soden, D. M., Larkin, J. O., Collins, C. G., Tangney, M., Aarons, S., Piggott, J., et al. (2006). Successful application of targeted electrochemotherapy using novel flexible electrodes and low dose bleomycin to solid tumours. Cancer Letters, 232(2), 300–310.PubMedCrossRef

157.

Miklavcic, D., Snoj, M., Zupanic, A., Kos, B., Cemazar, M., Kropivnik, M., et al. (2010). Towards treatment planning and treatment of deep-seated solid tumors by electrochemotherapy. Biomedical Engineering Online, 9(10), 1–12.

158.

Bianchi, G., Campanacci, L., Fini, M., Alberghini, M., & Mercuri, M. (2010). Electrochemotherapy for the treatment of osteolytic bone metastasis: a phase I/II clinical trial. In EMSOS 2010 Annual Meeting (pp. 5–7).

159.

Agerholm-Larsen, B., Iversen, H. K., Ibsen, P., Moller, J. M., Mahmood, F., Jensen, K. S., et al. (2011). Preclinical validation of electrochemotherapy as an effective treatment for brain tumors. Cancer Research, 71(11), 3753–3762.PubMedCrossRef

160.

Linnert, M., Iversen, H. K., & Gehl, J. (2012). Multiple brain metastases-current management and perspectives for treatment with electrochemotherapy. Radiology and Oncology, 46(4), 271–278.PubMedPubMedCentralCrossRef

161.

Mozzillo, N., Caracò, C., Mori, S., Di Monta, G., Botti, G., Ascierto, P. A., et al. (2012). Use of neoadjuvant electrochemotherapy to treat a large metastatic lesion of the cheek in a patient with melanoma. Journal of Translational Medicine, 10(131), 2.

162.

Serša, G., Miklavčič, D., Čemažar, M., Belehradek, J., Jr., Jarm, T., & Mir, L. M. (1997). Electrochemotherapy with CDDP on LPB sarcoma: comparison of the anti-tumor effectiveness in immunocompotent and immunodeficient mice. Bioelectrochemistry and Bioenergetics, 43(2), 279–283.

163.

Gerlini, G., Di Gennaro, P., & Borgognoni, L. (2012). Enhancing anti-melanoma immunity by electrochemotherapy and in vivo dendritic-cell activation. Oncoimmunology, 1(9), 1655–1657.PubMedPubMedCentralCrossRef

164.

Widera, G., Austin, M., Rabussay, D., Goldbeck, C., Barnett, S. W., Chen, M., et al. (2000). Increased DNA vaccine delivery and immunogenicity by electroporation in vivo. The Journal of Immunology, 164(9), 4635–4640.PubMedCrossRef

165.

Calvet, C. Y., Famin, D., Andre, F. M., & Mir, L. M. (2014). Electrochemotherapy with bleomycin induces hallmarks of immunogenic cell death in murine colon cancer cells. Oncoimmunology, 3(4), e28131.PubMedPubMedCentralCrossRef

166.

Gerlini, G., Sestini, S., Di Gennaro, P., Urso, C., Pimpinelli, N., & Borgognoni, L. (2013). Dendritic cells recruitment in melanoma metastasis treated by electrochemotherapy. Clinical & Experimental Metastasis, 30(1), 37–45.CrossRef

167.

Simeone, E., Benedetto, L., Gentilcore, G., Capone, M., Caracò, C., Di Monta, G., et al. (2014). Combination therapy with ipilimumab and electrochemotherapy: preliminary efficacy results and correlation with immunological parameters. Journal of Translational Medicine, 12(Suppl 1), O5.PubMedCentralCrossRef

168.

Miklavčič, D., Mali, B., Kos, B., Heller, R., & Serša, G. (2014). Electrochemotherapy: from the drawing board into medical practice. Biomedical Engineering Online, 13(1), 29.PubMedPubMedCentralCrossRef

169.

Jemal, A., Bray, F., Center, M. M., Ferlay, J., Ward, E., & Forman, D. (2011). Global cancer statistics. CA: a Cancer Journal for Clinicians, 61(2), 69–90.

170.

Molina, J.R., Yang, P., Cassivi, S.D., Schild, S.E., & Adjei, A.A. (2008). Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. In Mayo Clinic proceedings (vol. 83, pp. 584–594, vol. 5). Elsevier.

Titel: Low immunogenicity in non-small cell lung cancer; do new developments and novel treatments have a role?
verfasst von: R. E. Gardiner
S. Jahangeer
P. Forde
A. B. Ariffin
B. Bird
D. Soden
J. Hinchion
Publikationsdatum: 01.03.2015
Verlag: Springer US
Erschienen in: Cancer and Metastasis Reviews / Ausgabe 1/2015
Print ISSN: 0167-7659
Elektronische ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-015-9550-8

Springer Medizin

Low immunogenicity in non-small cell lung cancer; do new developments and novel treatments have a role?

Abstract

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 1/2015

Primary debulking surgery and neoadjuvant chemotherapy in the treatment of advanced epithelial ovarian carcinoma

Biographies

Exploring alternative ovarian cancer biomarkers using innovative nanotechnology strategies

Role of the folate receptor in ovarian cancer treatment: evidence, mechanism, and clinical implications

The conflicting roles of tumor stroma in pancreatic cancer and their contribution to the failure of clinical trials: a systematic review and critical appraisal

Preface

Neu im Fachgebiet Onkologie

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

Update Onkologie