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Cancer and Metastasis Reviews

Erschienen in:

01.03.2011

How to improve the immunogenicity of chemotherapy and radiotherapy

verfasst von: Yuting Ma, Rosa Conforti, Laetitia Aymeric, Clara Locher, Oliver Kepp, Guido Kroemer, Laurence Zitvogel

Erschienen in: Cancer and Metastasis Reviews | Ausgabe 1/2011

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Abstract

Chemotherapy or radiotherapy could induce various tumor cell death modalities, releasing tumor-derived antigen as well as danger signals that could either be captured for triggering antitumor immune response or ignored. Exploring the interplay among therapeutic drugs, tumor cell death and the immune cells should improve diagnostic, prognostic, predictive, and therapeutic management of tumor. We summarized some of the cell death-derived danger signals and the mechanism for host to sense and response to cell death in the tumor microenvironment. Based on the recent clinical or experimental findings, several strategies have been suggested to improve the immunogenicity of cell death and augment antitumor immunity.

Hodi, F. S., & Dranoff, G. (2006). Combinatorial cancer immunotherapy. Advances in Immunology, 90, 341–368. doi:10.1016/S0065-2776(06)90009-1.PubMed

Soiffer, R., Hodi, F. S., Haluska, F., Jung, K., Gillessen, S., Singer, S., et al. (2003). Vaccination with irradiated, autologous melanoma cells engineered to secrete granulocyte–macrophage colony-stimulating factor by adenoviral-mediated gene transfer augments antitumor immunity in patients with metastatic melanoma. Journal of Clinical Oncology, 21(17), 3343–3350. doi:10.1200/JCO.2003.07.005.PubMed

Salgia, R., Lynch, T., Skarin, A., Lucca, J., Lynch, C., Jung, K., et al. (2003). Vaccination with irradiated autologous tumor cells engineered to secrete granulocyte–macrophage colony-stimulating factor augments antitumor immunity in some patients with metastatic non-small-cell lung carcinoma. Journal of Clinical Oncology, 21(4), 624–630.PubMed

Perez, C. A., Fu, A., Onishko, H., Hallahan, D. E., & Geng, L. (2009). Radiation induces an antitumour immune response to mouse melanoma. International Journal of Radiation Biology, 85(12), 1126–1136. doi:10.3109/09553000903242099.PubMed

Casares, N., Pequignot, M. O., Tesniere, A., Ghiringhelli, F., Roux, S., Chaput, N., et al. (2005). Caspase-dependent immunogenicity of doxorubicin-induced tumor cell death. The Journal of Experimental Medicine, 202(12), 1691–1701. doi:10.1084/jem.20050915.PubMed

Obeid, M., Tesniere, A., Ghiringhelli, F., Fimia, G. M., Apetoh, L., Perfettini, J. L., et al. (2007). Calreticulin exposure dictates the immunogenicity of cancer cell death. Natural Medicines, 13(1), 54–61. doi:10.1038/nm1523.

Chiarle, R., Martinengo, C., Mastini, C., Ambrogio, C., D’Escamard, V., Forni, G., et al. (2008). The anaplastic lymphoma kinase is an effective oncoantigen for lymphoma vaccination. Natural Medicines, 14(6), 676–680. doi:10.1038/nm1769.

Correale, P., Cusi, M. G., Tsang, K. Y., Del Vecchio, M. T., Marsili, S., Placa, M. L., et al. (2005). Chemo-immunotherapy of metastatic colorectal carcinoma with gemcitabine plus FOLFOX 4 followed by subcutaneous granulocyte macrophage colony-stimulating factor and interleukin-2 induces strong immunologic and antitumor activity in metastatic colon cancer patients. Journal of Clinical Oncology, 23(35), 8950–8958. doi:10.1200/JCO.2005.12.147.PubMed

Ma, Y., Kepp, O., Ghiringhelli, F., Apetoh, L., Aymeric, L., Locher, C., et al. (2010). Chemotherapy and radiotherapy: Cryptic anticancer vaccines. Seminars in Immunology, 22(3), 113–124. doi:10.1016/j.smim.2010.03.001.PubMed

10.

Imaeda, A. B., Watanabe, A., Sohail, M. A., Mahmood, S., Mohamadnejad, M., Sutterwala, F. S., et al. (2009). Acetaminophen-induced hepatotoxicity in mice is dependent on Tlr9 and the Nalp3 inflammasome. Journal of Clinical Investigation, 119(2), 305–314. doi:10.1172/JCI35958.PubMed

11.

Scaffidi, P., Misteli, T., & Bianchi, M. E. (2002). Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature, 418(6894), 191–195. doi:10.1038/nature00858.PubMed

12.

Yamasaki, S., Ishikawa, E., Sakuma, M., Hara, H., Ogata, K., & Saito, T. (2008). Mincle is an ITAM-coupled activating receptor that senses damaged cells. Nature Immunology, 9(10), 1179–1188. doi:10.1038/ni.1651.PubMed

13.

Foell, D., Wittkowski, H., Vogl, T., & Roth, J. (2007). S100 proteins expressed in phagocytes: A novel group of damage-associated molecular pattern molecules. Journal of Leukocyte Biology, 81(1), 28–37. doi:10.1189/jlb.0306170.PubMed

14.

Barrat, F. J., Meeker, T., Gregorio, J., Chan, J. H., Uematsu, S., Akira, S., et al. (2005). Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus. The Journal of Experimental Medicine, 202(8), 1131–1139. doi:10.1084/jem.20050914.PubMed

15.

Osterloh, A., Veit, A., Gessner, A., Fleischer, B., & Breloer, M. (2008). Hsp60-mediated T cell stimulation is independent of TLR4 and IL-12. International Immunology, 20(3), 433–443. doi:10.1093/intimm/dxn003.PubMed

16.

Basu, S., Binder, R. J., Ramalingam, T., & Srivastava, P. K. (2001). CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Immunity, 14(3), 303–313.PubMed

17.

Rock, K. L., Latz, E., Ontiveros, F., & Kono, H. (2010). The sterile inflammatory response. Annual Review of Immunology, 28, 321–342. doi:10.1146/annurev-immunol-030409-101311.PubMed

18.

Chen, C. J., Kono, H., Golenbock, D., Reed, G., Akira, S., & Rock, K. L. (2007). Identification of a key pathway required for the sterile inflammatory response triggered by dying cells. Natural Medicines, 13(7), 851–856. doi:10.1038/nm1603.

19.

Distler, J. H., Huber, L. C., Gay, S., Distler, O., & Pisetsky, D. S. (2006). Microparticles as mediators of cellular cross-talk in inflammatory disease. Autoimmunity, 39(8), 683–690. doi:10.1080/08916930601061538.PubMed

20.

Peter, C., Waibel, M., Radu, C. G., Yang, L. V., Witte, O. N., Schulze-Osthoff, K., et al. (2008). Migration to apoptotic “find-me” signals is mediated via the phagocyte receptor G2A. The Journal of Biological Chemistry, 283(9), 5296–5305. doi:10.1074/jbc.M706586200.PubMed

21.

Lauber, K., Bohn, E., Krober, S. M., Xiao, Y. J., Blumenthal, S. G., Lindemann, R. K., et al. (2003). Apoptotic cells induce migration of phagocytes via caspase-3-mediated release of a lipid attraction signal. Cell, 113(6), 717–730.PubMed

22.

Yang, D., Chen, Q., Yang, H., Tracey, K. J., Bustin, M., & Oppenheim, J. J. (2007). High mobility group box-1 protein induces the migration and activation of human dendritic cells and acts as an alarmin. Journal of Leukocyte Biology, 81(1), 59–66. doi:10.1189/jlb.0306180.PubMed

23.

Orlova, V. V., Choi, E. Y., Xie, C., Chavakis, E., Bierhaus, A., Ihanus, E., et al. (2007). A novel pathway of HMGB1-mediated inflammatory cell recruitment that requires Mac-1-integrin. The EMBO Journal, 26(4), 1129–1139. doi:10.1038/sj.emboj.7601552.PubMed

24.

Apetoh, L., Ghiringhelli, F., Tesniere, A., Obeid, M., Ortiz, C., Criollo, A., et al. (2007). Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Natural Medicines, 13(9), 1050–1059. doi:10.1038/nm1622.

25.

Elliott, M. R., Chekeni, F. B., Trampont, P. C., Lazarowski, E. R., Kadl, A., Walk, S. F., et al. (2009). Nucleotides released by apoptotic cells act as a find-me signal to promote phagocytic clearance. Nature, 461(7261), 282–286. doi:10.1038/nature08296.PubMed

26.

Gude, D. R., Alvarez, S. E., Paugh, S. W., Mitra, P., Yu, J., Griffiths, R., et al. (2008). Apoptosis induces expression of sphingosine kinase 1 to release sphingosine-1-phosphate as a “come-and-get-me” signal. The FASEB Journal, 22(8), 2629–2638. doi:10.1096/fj.08-107169.PubMed

27.

Mesaeli, N., & Phillipson, C. (2004). Impaired p53 expression, function, and nuclear localization in calreticulin-deficient cells. Molecular Biology of the Cell, 15(4), 1862–1870. doi:10.1091/mbc.E03-04-0251.PubMed

28.

Gardai, S. J., McPhillips, K. A., Frasch, S. C., Janssen, W. J., Starefeldt, A., Murphy-Ullrich, J. E., et al. (2005). Cell-surface calreticulin initiates clearance of viable or apoptotic cells through trans-activation of LRP on the phagocyte. Cell, 123(2), 321–334. doi:10.1016/j.cell.2005.08.032.PubMed

29.

Obeid, M., Tesniere, A., Panaretakis, T., Tufi, R., Joza, N., van Endert, P., et al. (2007). Ecto-calreticulin in immunogenic chemotherapy. Immunological Reviews, 220, 22–34. doi:10.1111/j.1600-065X.2007.00567.x.PubMed

30.

Obeid, M., Panaretakis, T., Joza, N., Tufi, R., Tesniere, A., van Endert, P., et al. (2007). Calreticulin exposure is required for the immunogenicity of gamma-irradiation and UVC light-induced apoptosis. Cell Death and Differentiation, 14(10), 1848–1850. doi:10.1038/sj.cdd.4402201.PubMed

31.

Panaretakis, T., Joza, N., Modjtahedi, N., Tesniere, A., Vitale, I., Durchschlag, M., et al. (2008). The co-translocation of ERp57 and calreticulin determines the immunogenicity of cell death. Cell Death and Differentiation, 15(9), 1499–1509. doi:10.1038/cdd.2008.67.PubMed

32.

Panaretakis, T., Kepp, O., Brockmeier, U., Tesniere, A., Bjorklund, A. C., Chapman, D. C., et al. (2009). Mechanisms of pre-apoptotic calreticulin exposure in immunogenic cell death. The EMBO Journal, 28(5), 578–590. doi:10.1038/emboj.2009.1.PubMed

33.

Garrido, C., Brunet, M., Didelot, C., Zermati, Y., Schmitt, E., & Kroemer, G. (2006). Heat shock proteins 27 and 70: Anti-apoptotic proteins with tumorigenic properties. Cell Cycle, 5(22), 2592–2601.PubMed

34.

Lanneau, D., Brunet, M., Frisan, E., Solary, E., Fontenay, M., & Garrido, C. (2008). Heat shock proteins: Essential proteins for apoptosis regulation. Journal of Cellular and Molecular Medicine, 12(3), 743–761. doi:10.1111/j.1582-4934.2008.00273.x.PubMed

35.

Spisek, R., & Dhodapkar, M. V. (2007). Towards a better way to die with chemotherapy: Role of heat shock protein exposure on dying tumor cells. Cell Cycle, 6(16), 1962–1965.PubMed

36.

Tesniere, A., Panaretakis, T., Kepp, O., Apetoh, L., Ghiringhelli, F., Zitvogel, L., et al. (2008). Molecular characteristics of immunogenic cancer cell death. Cell Death and Differentiation, 15(1), 3–12. doi:10.1038/sj.cdd.4402269.PubMed

37.

Doody, A. D., Kovalchin, J. T., Mihalyo, M. A., Hagymasi, A. T., Drake, C. G., & Adler, A. J. (2004). Glycoprotein 96 can chaperone both MHC class I- and class II-restricted epitopes for in vivo presentation, but selectively primes CD8⁺ T cell effector function. Journal of Immunology, 172(10), 6087–6092.

38.

Murshid, A., Gong, J., & Calderwood, S. K. (2010). Heat shock protein 90 mediates efficient antigen cross presentation through the scavenger receptor expressed by endothelial cells-I. Journal of Immunology, 185(5), 2903–2917. doi:10.4049/jimmunol.0903635.

39.

Chan, T., Chen, Z., Hao, S., Xu, S., Yuan, J., Saxena, A., et al. (2007). Enhanced T-cell immunity induced by dendritic cells with phagocytosis of heat shock protein 70 gene-transfected tumor cells in early phase of apoptosis. Cancer Gene Therapy, 14(4), 409–420. doi:10.1038/sj.cgt.7701025.PubMed

40.

Elsner, L., Flugge, P. F., Lozano, J., Muppala, V., Eiz-Vesper, B., Demiroglu, S. Y., et al. (2010). The endogenous danger signals HSP70 and MICA cooperate in the activation of cytotoxic effector functions of NK cells. Journal of Cellular and Molecular Medicine, 14(4), 992–1002. doi:10.1111/j.1582-4934.2009.00677.x.PubMed

41.

Fionda, C., Soriani, A., Malgarini, G., Iannitto, M. L., Santoni, A., & Cippitelli, M. (2009). Heat shock protein-90 inhibitors increase MHC class I-related chain A and B ligand expression on multiple myeloma cells and their ability to trigger NK cell degranulation. Journal of Immunology, 183(7), 4385–4394. doi:10.4049/jimmunol.0901797.

42.

Dhodapkar, M. V., Dhodapkar, K. M., & Li, Z. (2008). Role of chaperones and FcgammaR in immunogenic death. Current Opinion in Immunology, 20(5), 512–517. doi:10.1016/j.coi.2008.05.002.PubMed

43.

Wang, X. Y., Sun, X., Chen, X., Facciponte, J., Repasky, E. A., Kane, J., et al. (2010). Superior antitumor response induced by large stress protein chaperoned protein antigen compared with peptide antigen. Journal of Immunology, 184(11), 6309–6319. doi:10.4049/jimmunol.0903891.

44.

Kobayashi, N., Karisola, P., Pena-Cruz, V., Dorfman, D. M., Jinushi, M., Umetsu, S. E., et al. (2007). TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of apoptotic cells. Immunity, 27(6), 927–940. doi:10.1016/j.immuni.2007.11.011.PubMed

45.

Gonzalez, N., Bensinger, S. J., Hong, C., Beceiro, S., Bradley, M. N., Zelcer, N., et al. (2009). Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR. Immunity, 31(2), 245–258. doi:10.1016/j.immuni.2009.06.018.

46.

Shao, W. H., Zhen, Y., Eisenberg, R. A., & Cohen, P. L. (2009). The Mer receptor tyrosine kinase is expressed on discrete macrophage subpopulations and mainly uses Gas6 as its ligand for uptake of apoptotic cells. Clinical Immunology, 133(1), 138–144. doi:10.1016/j.clim.2009.06.002.PubMed

47.

Scott, R. S., McMahon, E. J., Pop, S. M., Reap, E. A., Caricchio, R., Cohen, P. L., et al. (2001). Phagocytosis and clearance of apoptotic cells is mediated by MER. Nature, 411(6834), 207–211. doi:10.1038/35075603.PubMed

48.

Jinushi, M., Sato, M., Kanamoto, A., Itoh, A., Nagai, S., Koyasu, S., et al. (2009). Milk fat globule epidermal growth factor-8 blockade triggers tumor destruction through coordinated cell-autonomous and immune-mediated mechanisms. The Journal of Experimental Medicine, 206(6), 1317–1326. doi:10.1084/jem.20082614.PubMed

49.

Asano, K., Miwa, M., Miwa, K., Hanayama, R., Nagase, H., Nagata, S., et al. (2004). Masking of phosphatidylserine inhibits apoptotic cell engulfment and induces autoantibody production in mice. The Journal of Experimental Medicine, 200(4), 459–467. doi:10.1084/jem.20040342.PubMed

50.

Park, D., Tosello-Trampont, A. C., Elliott, M. R., Lu, M., Haney, L. B., Ma, Z., et al. (2007). BAI1 is an engulfment receptor for apoptotic cells upstream of the ELMO/Dock180/Rac module. Nature, 450(7168), 430–434. doi:10.1038/nature06329.PubMed

51.

Jinushi, M., Nakazaki, Y., Dougan, M., Carrasco, D. R., Mihm, M., & Dranoff, G. (2007). MFG-E8-mediated uptake of apoptotic cells by APCs links the pro- and antiinflammatory activities of GM-CSF. Journal of Clinical Investigation, 117(7), 1902–1913. doi:10.1172/JCI30966.PubMed

52.

Linger, R. M., Keating, A. K., Earp, H. S., & Graham, D. K. (2008). TAM receptor tyrosine kinases: Biologic functions, signaling, and potential therapeutic targeting in human cancer. Advances in Cancer Research, 100, 35–83. doi:10.1016/S0065-230X(08)00002-X.PubMed

53.

Sen, P., Wallet, M. A., Yi, Z., Huang, Y., Henderson, M., Mathews, C. E., et al. (2007). Apoptotic cells induce Mer tyrosine kinase-dependent blockade of NF-kappaB activation in dendritic cells. Blood, 109(2), 653–660. doi:10.1182/blood-2006-04-017368.PubMed

54.

Brown, G. D. (2008). Sensing necrosis with Mincle. Nature Immunology, 9(10), 1099–1100. doi:10.1038/ni1008-1099.PubMed

55.

Hildner, K., Edelson, B. T., Purtha, W. E., Diamond, M., Matsushita, H., Kohyama, M., et al. (2008). Batf3 deficiency reveals a critical role for CD8alpha⁺ dendritic cells in cytotoxic T cell immunity. Science, 322(5904), 1097–1100. doi:10.1126/science.1164206.PubMed

56.

Dudziak, D., Kamphorst, A. O., Heidkamp, G. F., Buchholz, V. R., Trumpfheller, C., Yamazaki, S., et al. (2007). Differential antigen processing by dendritic cell subsets in vivo. Science, 315(5808), 107–111. doi:10.1126/science.1136080.PubMed

57.

Schnorrer, P., Behrens, G. M., Wilson, N. S., Pooley, J. L., Smith, C. M., El-Sukkari, D., et al. (2006). The dominant role of CD8⁺ dendritic cells in cross-presentation is not dictated by antigen capture. Proceedings of the National Academy of Sciences of the United States of America, 103(28), 10729–10734. doi:10.1073/pnas.0601956103.PubMed

58.

McDonnell, A. M., Prosser, A. C., van Bruggen, I., Robinson, B. W., & Currie, A. J. (2010). CD8alpha⁺ DC are not the sole subset cross-presenting cell-associated tumor antigens from a solid tumor. European Journal of Immunology, 40(6), 1617–1627. doi:10.1002/eji.200940153.PubMed

59.

Merad, M., Ginhoux, F., & Collin, M. (2008). Origin, homeostasis and function of Langerhans cells and other Langerin-expressing dendritic cells. Nature Reviews. Immunology, 8(12), 935–947. doi:10.1038/nri2455.PubMed

60.

Idoyaga, J., Suda, N., Suda, K., Park, C. G., & Steinman, R. M. (2009). Antibody to Langerin/CD207 localizes large numbers of CD8alpha⁺ dendritic cells to the marginal zone of mouse spleen. Proceedings of the National Academy of Sciences of the United States of America, 106(5), 1524–1529. doi:10.1073/pnas.0812247106.PubMed

61.

Flacher, V., Douillard, P., Ait-Yahia, S., Stoitzner, P., Clair-Moninot, V., Romani, N., et al. (2008). Expression of Langerin/CD207 reveals dendritic cell heterogeneity between inbred mouse strains. Immunology, 123(3), 339–347. doi:10.1111/j.1365-2567.2007.02785.x.PubMed

62.

Idoyaga, J., Cheong, C., Suda, K., Suda, N., Kim, J. Y., Lee, H., et al. (2008). Cutting edge: Langerin/CD207 receptor on dendritic cells mediates efficient antigen presentation on MHC I and II products in vivo. Journal of Immunology, 180(6), 3647–3650.

63.

Lin, M. L., Zhan, Y., Proietto, A. I., Prato, S., Wu, L., Heath, W. R., et al. (2008). Selective suicide of cross-presenting CD8⁺ dendritic cells by cytochrome c injection shows functional heterogeneity within this subset. Proceedings of the National Academy of Sciences of the United States of America, 105(8), 3029–3034. doi:10.1073/pnas.0712394105.PubMed

64.

Farrand, K. J., Dickgreber, N., Stoitzner, P., Ronchese, F., Petersen, T. R., & Hermans, I. F. (2009). Langerin⁺ CD8alpha⁺ dendritic cells are critical for cross-priming and IL-12 production in response to systemic antigens. Journal of Immunology, 183(12), 7732–7742. doi:10.4049/jimmunol.0902707.

65.

Henri, S., Poulin, L. F., Tamoutounour, S., Ardouin, L., Guilliams, M., de Bovis, B., et al. (2010). CD207⁺ CD103⁺ dermal dendritic cells cross-present keratinocyte-derived antigens irrespective of the presence of Langerhans cells. The Journal of Experimental Medicine, 207(1), 189–206. doi:10.1084/jem.20091964.PubMed

66.

Backer, R., Schwandt, T., Greuter, M., Oosting, M., Jungerkes, F., Tuting, T., et al. (2010). Effective collaboration between marginal metallophilic macrophages and CD8⁺ dendritic cells in the generation of cytotoxic T cells. Proceedings of the National Academy of Sciences of the United States of America, 107(1), 216–221. doi:10.1073/pnas.0909541107.PubMed

67.

Zhang, B. (2008). Targeting the stroma by T cells to limit tumor growth. Cancer Research, 68(23), 9570–9573. doi:10.1158/0008-5472.CAN-08-2414.PubMed

68.

Zhang, B., Bowerman, N. A., Salama, J. K., Schmidt, H., Spiotto, M. T., Schietinger, A., et al. (2007). Induced sensitization of tumor stroma leads to eradication of established cancer by T cells. The Journal of Experimental Medicine, 204(1), 49–55. doi:10.1084/jem.20062056.PubMed

69.

Schietinger, A., Philip, M., Liu, R. B., Schreiber, K., & Schreiber, H. (2010). Bystander killing of cancer requires the cooperation of CD4⁺ and CD8⁺ T cells during the effector phase. Journal of Experimental Medicine, 207, 2469–2477. doi:10.1084/jem.20092450.PubMed

70.

Spiotto, M. T., Rowley, D. A., & Schreiber, H. (2004). Bystander elimination of antigen loss variants in established tumors. Natural Medicines, 10(3), 294–298. doi:10.1038/nm999.

71.

Wu, Y., Wu, W., Wong, W. M., Ward, E., Thrasher, A. J., Goldblatt, D., et al. (2009). Human gamma delta T cells: A lymphoid lineage cell capable of professional phagocytosis. Journal of Immunology, 183(9), 5622–5629. doi:10.4049/jimmunol.0901772.

72.

Brandes, M., Willimann, K., Bioley, G., Levy, N., Eberl, M., Luo, M., et al. (2009). Cross-presenting human gammadelta T cells induce robust CD8⁺ alphabeta T cell responses. Proceedings of the National Academy of Sciences of the United States of America, 106(7), 2307–2312. doi:10.1073/pnas.0810059106.PubMed

73.

Melief, C. J. (2008). Cancer immunotherapy by dendritic cells. Immunity, 29(3), 372–383. doi:10.1016/j.immuni.2008.08.004.PubMed

74.

Saccheri, F., Pozzi, C., Avogadri, F., Barozzi, S., Faretta, M., Fusi, P., et al. (2010). Bacteria-induced gap junctions in tumors favor antigen cross-presentation and antitumor immunity. Science Translational Medicine, 2(44), 4457. doi:10.1126/scitranslmed.3000739.

75.

de Visser, K. E., Eichten, A., & Coussens, L. M. (2006). Paradoxical roles of the immune system during cancer development. Nature Reviews Cancer, 6(1), 24–37. doi:10.1038/nrc1782.PubMed

76.

Lakshmikanth, T., Burke, S., Ali, T. H., Kimpfler, S., Ursini, F., Ruggeri, L., et al. (2009). NCRs and DNAM-1 mediate NK cell recognition and lysis of human and mouse melanoma cell lines in vitro and in vivo. Journal of Clinical Investigation, 119(5), 1251–1263. doi:10.1172/JCI36022.PubMed

77.

Chan, C. J., Andrews, D. M., McLaughlin, N. M., Yagita, H., Gilfillan, S., Colonna, M., et al. (2010). DNAM-1/CD155 interactions promote cytokine and NK cell-mediated suppression of poorly immunogenic melanoma metastases. Journal of Immunology, 184(2), 902–911. doi:10.4049/jimmunol.0903225.

78.

Carlsten, M., Baumann, B. C., Simonsson, M., Jadersten, M., Forsblom, A. M., Hammarstedt, C., et al. (2010). Reduced DNAM-1 expression on bone marrow NK cells associated with impaired killing of CD34⁺ blasts in myelodysplastic syndrome. Leukemia, 24(9), 1607–1616. doi:10.1038/leu.2010.149.PubMed

79.

Diefenbach, A., Jensen, E. R., Jamieson, A. M., & Raulet, D. H. (2001). Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity. Nature, 413(6852), 165–171. doi:10.1038/35093109.PubMed

80.

Soriani, A., Zingoni, A., Cerboni, C., Iannitto, M. L., Ricciardi, M. R., Di Gialleonardo, V., et al. (2009). ATM-ATR-dependent up-regulation of DNAM-1 and NKG2D ligands on multiple myeloma cells by therapeutic agents results in enhanced NK-cell susceptibility and is associated with a senescent phenotype. Blood, 113(15), 3503–3511. doi:10.1182/blood-2008-08-173914.PubMed

81.

Kato, N., Tanaka, J., Sugita, J., Toubai, T., Miura, Y., Ibata, M., et al. (2007). Regulation of the expression of MHC class I-related chain A, B (MICA, MICB) via chromatin remodeling and its impact on the susceptibility of leukemic cells to the cytotoxicity of NKG2D-expressing cells. Leukemia, 21(10), 2103–2108. doi:10.1038/sj.leu.2404862.PubMed

82.

Schmudde, M., Braun, A., Pende, D., Sonnemann, J., Klier, U., Beck, J. F., et al. (2008). Histone deacetylase inhibitors sensitize tumour cells for cytotoxic effects of natural killer cells. Cancer Letters, 272(1), 110–121. doi:10.1016/j.canlet.2008.06.027.PubMed

83.

Fine, J. H., Chen, P., Mesci, A., Allan, D. S., Gasser, S., Raulet, D. H., et al. (2010). Chemotherapy-induced genotoxic stress promotes sensitivity to natural killer cell cytotoxicity by enabling missing-self recognition. Cancer Research, 70(18), 7102–7113. doi:10.1158/0008-5472.CAN-10-1316.PubMed

84.

Rey, J., Veuillen, C., Vey, N., Bouabdallah, R., & Olive, D. (2009). Natural killer and gammadelta T cells in haematological malignancies: Enhancing the immune effectors. Trends in Molecular Medicine, 15(6), 275–284. doi:10.1016/j.molmed.2009.04.005.PubMed

85.

Pages, F., Galon, J., Dieu-Nosjean, M. C., Tartour, E., Sautes-Fridman, C., & Fridman, W. H. (2010). Immune infiltration in human tumors: A prognostic factor that should not be ignored. Oncogene, 29(8), 1093–1102. doi:10.1038/onc.2009.416.PubMed

86.

Ghiringhelli, F., Apetoh, L., Tesniere, A., Aymeric, L., Ma, Y., Ortiz, C., et al. (2009). Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Natural Medicines, 15(10), 1170–1178. doi:10.1038/nm.2028.

87.

Lee, Y., Auh, S. L., Wang, Y., Burnette, B., Meng, Y., Beckett, M., et al. (2009). Therapeutic effects of ablative radiation on local tumor require CD8⁺ T cells: Changing strategies for cancer treatment. Blood, 114(3), 589–595. doi:10.1182/blood-2009-02-206870.PubMed

88.

Takeshima, T., Chamoto, K., Wakita, D., Ohkuri, T., Togashi, Y., Shirato, H., et al. (2010). Local radiation therapy inhibits tumor growth through the generation of tumor-specific CTL: Its potentiation by combination with Th1 cell therapy. Cancer Research, 70(7), 2697–2706. doi:10.1158/0008-5472.CAN-09-2982.PubMed

89.

Johansson, M., Denardo, D. G., & Coussens, L. M. (2008). Polarized immune responses differentially regulate cancer development. Immunological Reviews, 222, 145–154. doi:10.1111/j.1600-065X.2008.00600.x.PubMed

90.

DeNardo, D. G., Johansson, M., & Coussens, L. M. (2008). Immune cells as mediators of solid tumor metastasis. Cancer and Metastasis Reviews, 27(1), 11–18. doi:10.1007/s10555-007-9100-0.PubMed

91.

Zou, W. (2005). Immunosuppressive networks in the tumour environment and their therapeutic relevance. Nature Reviews Cancer, 5(4), 263–274. doi:10.1038/nrc1586.PubMed

92.

Zea, A. H., Rodriguez, P. C., Atkins, M. B., Hernandez, C., Signoretti, S., Zabaleta, J., et al. (2005). Arginase-producing myeloid suppressor cells in renal cell carcinoma patients: A mechanism of tumor evasion. Cancer Research, 65(8), 3044–3048. doi:10.1158/0008-5472.CAN-04-4505.PubMed

93.

Serafini, P., De Santo, C., Marigo, I., Cingarlini, S., Dolcetti, L., Gallina, G., et al. (2004). Derangement of immune responses by myeloid suppressor cells. Cancer Immunology, Immunotherapy, 53(2), 64–72. doi:10.1007/s00262-003-0443-2.PubMed

94.

Gabrilovich, D. I., & Nagaraj, S. (2009). Myeloid-derived suppressor cells as regulators of the immune system. Nature Reviews Immunology, 9(3), 162–174. doi:10.1038/nri2506.PubMed

95.

Chalmin, F., Ladoire, S., Mignot, G., Vincent, J., Bruchard, M., Remy-Martin, J. P., et al. (2010). Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. Journal of Clinical Investigation, 120(2), 457–471. doi:10.1172/JCI40483.PubMed

96.

Ostrand-Rosenberg, S. (2010). Myeloid-derived suppressor cells: More mechanisms for inhibiting antitumor immunity. Cancer Immunology Immunotherapy, 59(10), 1593–1600. doi:10.1007/s00262-010-0855-8.

97.

Nagaraj, S., Schrum, A. G., Cho, H. I., Celis, E., & Gabrilovich, D. I. (2010). Mechanism of T cell tolerance induced by myeloid-derived suppressor cells. Journal of Immunology, 184(6), 3106–3116. doi:10.4049/jimmunol.0902661.

98.

Gobert, M., Treilleux, I., Bendriss-Vermare, N., Bachelot, T., Goddard-Leon, S., Arfi, V., et al. (2009). Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome. Cancer Research, 69(5), 2000–2009. doi:10.1158/0008-5472.CAN-08-2360.PubMed

99.

Menetrier-Caux, C., Gobert, M., & Caux, C. (2009). Differences in tumor regulatory T-cell localization and activation status impact patient outcome. Cancer Research, 69(20), 7895–7898. doi:10.1158/0008-5472.CAN-09-1642.PubMed

100.

Tan, M. C., Goedegebuure, P. S., Belt, B. A., Flaherty, B., Sankpal, N., Gillanders, W. E., et al. (2009). Disruption of CCR5-dependent homing of regulatory T cells inhibits tumor growth in a murine model of pancreatic cancer. Journal of Immunology, 182(3), 1746–1755.

101.

Ramakrishnan, R., Assudani, D., Nagaraj, S., Hunter, T., Cho, H. I., Antonia, S., et al. (2010). Chemotherapy enhances tumor cell susceptibility to CTL-mediated killing during cancer immunotherapy in mice. Journal of Clinical Investigation, 120(4), 1111–1124. doi:10.1172/JCI40269.PubMed

102.

Machiels, J. P., Reilly, R. T., Emens, L. A., Ercolini, A. M., Lei, R. Y., Weintraub, D., et al. (2001). Cyclophosphamide, doxorubicin, and paclitaxel enhance the antitumor immune response of granulocyte/macrophage-colony stimulating factor-secreting whole-cell vaccines in HER-2/neu tolerized mice. Cancer Research, 61(9), 3689–3697.PubMed

103.

Ghiringhelli, F., Larmonier, N., Schmitt, E., Parcellier, A., Cathelin, D., Garrido, C., et al. (2004). CD4⁺CD25⁺ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative. European Journal of Immunology, 34(2), 336–344. doi:10.1002/eji.200324181.PubMed

104.

Roux, S., Apetoh, L., Chalmin, F., Ladoire, S., Mignot, G., Puig, P. E., et al. (2008). CD4⁺CD25⁺ Tregs control the TRAIL-dependent cytotoxicity of tumor-infiltrating DCs in rodent models of colon cancer. Journal of Clinical Investigation, 118(11), 3751–3761. doi:10.1172/JCI35890.PubMed

105.

Ghiringhelli, F., Menard, C., Puig, P. E., Ladoire, S., Roux, S., Martin, F., et al. (2007). Metronomic cyclophosphamide regimen selectively depletes CD4⁺CD25⁺ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunology, Immunotherapy, 56(5), 641–648. doi:10.1007/s00262-006-0225-8.PubMed

106.

Markasz, L., Skribek, H., Uhlin, M., Otvos, R., Flaberg, E., Eksborg, S., et al. (2008). Effect of frequently used chemotherapeutic drugs on cytotoxic activity of human cytotoxic T-lymphocytes. Journal of Immunotherapy, 31(3), 283–293. doi:10.1097/CJI.0b013e3181628b76.PubMed

107.

Ugel, S., Delpozzo, F., Desantis, G., Papalini, F., Simonato, F., Sonda, N., et al. (2009). Therapeutic targeting of myeloid-derived suppressor cells. Current Opinion in Pharmacology, 9(4), 470–481. doi:10.1016/j.coph.2009.06.014.PubMed

108.

Grivennikov, S. I., Greten, F. R., & Karin, M. (2010). Immunity, inflammation, and cancer. Cell, 140(6), 883–899. doi:10.1016/j.cell.2010.01.025.PubMed

109.

Luqmani, Y. A. (2005). Mechanisms of drug resistance in cancer chemotherapy. Medical Principles and Practice, 14(Suppl 1), 35–48. doi:10.1159/000086183.PubMed

110.

Serrone, L., & Hersey, P. (1999). The chemoresistance of human malignant melanoma: An update. Melanoma Research, 9(1), 51–58.PubMed

111.

Plati, J., Bucur, O., & Khosravi-Far, R. (2008). Dysregulation of apoptotic signaling in cancer: Molecular mechanisms and therapeutic opportunities. Journal of Cellular Biochemistry, 104(4), 1124–1149. doi:10.1002/jcb.21707.PubMed

112.

Trougakos, I. P., Lourda, M., Antonelou, M. H., Kletsas, D., Gorgoulis, V. G., Papassideri, I. S., et al. (2009). Intracellular clusterin inhibits mitochondrial apoptosis by suppressing p53-activating stress signals and stabilizing the cytosolic Ku70-Bax protein complex. Clinical Cancer Research, 15(1), 48–59. doi:10.1158/1078-0432.CCR-08-1805.PubMed

113.

Djeu, J. Y., & Wei, S. (2009). Clusterin and chemoresistance. Advances in Cancer Research, 105, 77–92. doi:10.1016/S0065-230X(09)05005-2.PubMed

114.

Keating, A. K., Kim, G. K., Jones, A. E., Donson, A. M., Ware, K., Mulcahy, J. M., et al. (2010). Inhibition of Mer and Axl receptor tyrosine kinases in astrocytoma cells leads to increased apoptosis and improved chemosensitivity. Molecular Cancer Therapeutics, 9(5), 1298–1307. doi:10.1158/1535-7163.MCT-09-0707.PubMed

115.

Tang, D., Lotze, M. T., Zeh, H. J., & Kang, R. (2010). The redox protein HMGB1 regulates cell death and survival in cancer treatment. Autophagy, 6(8), 1181–1183. doi:10.4161/auto.6.8.13367.PubMed

116.

Lin, C. I., Whang, E. E., Abramson, M. A., Donner, D. B., Bertagnolli, M. M., Moore, F. D., Jr., et al. (2009). Galectin-3 regulates apoptosis and doxorubicin chemoresistance in papillary thyroid cancer cells. Biochemical and Biophysical Research Communications, 379(2), 626–631. doi:10.1016/j.bbrc.2008.12.153.PubMed

117.

Schonthal, A. H. (2009). Endoplasmic reticulum stress and autophagy as targets for cancer therapy. Cancer Letters, 275(2), 163–169. doi:10.1016/j.canlet.2008.07.005.PubMed

118.

Jordan, C. T. (2010). Targeting myeloid leukemia stem cells. Science Translational Medicine, 2(31), 31ps21. doi:10.1126/scitranslmed.3000914.PubMed

119.

LaBarge, M. A. (2010). The difficulty of targeting cancer stem cell niches. Clinical Cancer Research, 16(12), 3121–3129. doi:10.1158/1078-0432.CCR-09-2933.PubMed

120.

Speiser, D. E., & Romero, P. (2010). Molecularly defined vaccines for cancer immunotherapy, and protective T cell immunity. Seminars in Immunology, 22(3), 144–154. doi:10.1016/j.smim.2010.03.004.PubMed

121.

Dubensky, T. W., Jr., & Reed, S. G. (2010). Adjuvants for cancer vaccines. Seminars in Immunology, 22(3), 155–161. doi:10.1016/j.smim.2010.04.007.PubMed

122.

Palucka, K., Ueno, H., Zurawski, G., Fay, J., & Banchereau, J. (2010). Building on dendritic cell subsets to improve cancer vaccines. Current Opinion in Immunology, 22(2), 258–263. doi:10.1016/j.coi.2010.02.010.PubMed

123.

Palucka, A. K., Ueno, H., Fay, J. W., & Banchereau, J. (2007). Taming cancer by inducing immunity via dendritic cells. Immunological Reviews, 220, 129–150. doi:10.1111/j.1600-065X.2007.00575.x.PubMed

124.

Chamoto, K., Takeshima, T., Wakita, D., Ohkuri, T., Ashino, S., Omatsu, T., et al. (2009). Combination immunotherapy with radiation and CpG-based tumor vaccination for the eradication of radio- and immuno-resistant lung carcinoma cells. Cancer Science, 100(5), 934–939. doi:10.1111/j.1349-7006.2009.01114.x.PubMed

125.

Conforti, R., Ma, Y., Morel, Y., Paturel, C., Terme, M., Viaud, S., et al. (2010). Opposing effects of Toll-like receptor (TLR3) signaling in tumors can be therapeutically uncoupled to optimize the anticancer efficacy of TLR3 ligands. Cancer Research, 70(2), 490–500. doi:10.1158/0008-5472.CAN-09-1890.PubMed

126.

Sharma, M. D., Baban, B., Chandler, P., Hou, D. Y., Singh, N., Yagita, H., et al. (2007). Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase. Journal of Clinical Investigation, 117(9), 2570–2582. doi:10.1172/JCI31911.PubMed

127.

Ou, X., Cai, S., Liu, P., Zeng, J., He, Y., Wu, X., et al. (2008). Enhancement of dendritic cell-tumor fusion vaccine potency by indoleamine-pyrrole 2,3-dioxygenase inhibitor, 1-MT. Journal of Cancer Research and Clinical Oncology, 134(5), 525–533. doi:10.1007/s00432-007-0315-9.PubMed

128.

Herrmann, A., Kortylewski, M., Kujawski, M., Zhang, C., Reckamp, K., Armstrong, B., et al. (2010). Targeting Stat3 in the myeloid compartment drastically improves the in vivo antitumor functions of adoptively transferred T cells. Cancer Research, 70(19), 7455–7464. doi:10.1158/0008-5472.CAN-10-0736.PubMed

129.

Nam, J. S., Terabe, M., Mamura, M., Kang, M. J., Chae, H., Stuelten, C., et al. (2008). An anti-transforming growth factor beta antibody suppresses metastasis via cooperative effects on multiple cell compartments. Cancer Research, 68(10), 3835–3843. doi:10.1158/0008-5472.CAN-08-0215.PubMed

130.

Wang, L., Yi, T., Kortylewski, M., Pardoll, D. M., Zeng, D., & Yu, H. (2009). IL-17 can promote tumor growth through an IL-6-Stat3 signaling pathway. The Journal of Experimental Medicine, 206(7), 1457–1464. doi:10.1084/jem.20090207.PubMed

131.

Yoshio-Hoshino, N., Adachi, Y., Aoki, C., Pereboev, A., Curiel, D. T., & Nishimoto, N. (2007). Establishment of a new interleukin-6 (IL-6) receptor inhibitor applicable to the gene therapy for IL-6-dependent tumor. Cancer Research, 67(3), 871–875. doi:10.1158/0008-5472.CAN-06-3641.PubMed

132.

Shinriki, S., Jono, H., Ota, K., Ueda, M., Kudo, M., Ota, T., et al. (2009). Humanized anti-interleukin-6 receptor antibody suppresses tumor angiogenesis and in vivo growth of human oral squamous cell carcinoma. Clinical Cancer Research, 15(17), 5426–5434. doi:10.1158/1078-0432.CCR-09-0287.PubMed

133.

Matsuzaki, J., Gnjatic, S., Mhawech-Fauceglia, P., Beck, A., Miller, A., Tsuji, T., et al. (2010). Tumor-infiltrating NY-ESO-1-specific CD8⁺ T cells are negatively regulated by LAG-3 and PD-1 in human ovarian cancer. Proceedings of the National Academy of Sciences of the United States of America, 107(17), 7875–7880. doi:10.1073/pnas.1003345107.PubMed

134.

Jin, H. T., Anderson, A. C., Tan, W. G., West, E. E., Ha, S. J., Araki, K., et al. (2010). Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection. Proceedings of the National Academy of Sciences of the United States of America, 107(33), 14733–14738. doi:10.1073/pnas.1009731107.PubMed

135.

Fourcade, J., Sun, Z., Benallaoua, M., Guillaume, P., Luescher, I. F., Sander, C., et al. (2010). Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8⁺ T cell dysfunction in melanoma patients. The Journal of Experimental Medicine, 207(10), 2175–2186. doi:10.1084/jem.20100637.PubMed

136.

Sakuishi, K., Apetoh, L., Sullivan, J. M., Blazar, B. R., Kuchroo, V. K., & Anderson, A. C. (2010). Targeting Tim-3 and PD-1 pathways to reverse T cell exhaustion and restore anti-tumor immunity. The Journal of Experimental Medicine, 207(10), 2187–2194. doi:10.1084/jem.20100643.PubMed

137.

Derre, L., Rivals, J. P., Jandus, C., Pastor, S., Rimoldi, D., Romero, P., et al. (2010). BTLA mediates inhibition of human tumor-specific CD8⁺ T cells that can be partially reversed by vaccination. Journal of Clinical Investigation, 120(1), 157–167. doi:10.1172/JCI40070.PubMed

138.

Robert, C., & Ghiringhelli, F. (2009). What is the role of cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma? The Oncologist, 14(8), 848–861. doi:10.1634/theoncologist.2009-0028.PubMed

139.

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. doi:10.1084/jem.20082492.PubMed

140.

Chen, H., Liakou, C. I., Kamat, A., Pettaway, C., Ward, J. F., Tang, D. N., et al. (2009). Anti-CTLA-4 therapy results in higher CD4⁺ICOShi T cell frequency and IFN-gamma levels in both nonmalignant and malignant prostate tissues. Proceedings of the National Academy of Sciences of the United States of America, 106(8), 2729–2734. doi:10.1073/pnas.0813175106.PubMed

141.

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 of the United States of America, 107(9), 4275–4280. doi:10.1073/pnas.0915174107.PubMed

142.

Westwood, J. A., Darcy, P. K., Guru, P. M., Sharkey, J., Pegram, H. J., Amos, S. M., et al. (2010). Three agonist antibodies in combination with high-dose IL-2 eradicate orthotopic kidney cancer in mice. Journal of Translational Medicine, 8, 42. doi:10.1186/1479-5876-8-42.PubMed

143.

Dudley, M. E., Yang, J. C., Sherry, R., Hughes, M. S., Royal, R., Kammula, U., et al. (2008). Adoptive cell therapy for patients with metastatic melanoma: Evaluation of intensive myeloablative chemoradiation preparative regimens. Journal of Clinical Oncology, 26(32), 5233–5239. doi:10.1200/JCO.2008.16.5449.PubMed

144.

Quezada, S. A., Simpson, T. R., Peggs, K. S., Merghoub, T., Vider, J., Fan, X., et al. (2010). Tumor-reactive CD4(+) T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts. The Journal of Experimental Medicine, 207(3), 637–650. doi:10.1084/jem.20091918.PubMed

145.

Garcia-Hernandez Mde, L., Hamada, H., Reome, J. B., Misra, S. K., Tighe, M. P., & Dutton, R. W. (2010). Adoptive transfer of tumor-specific Tc17 effector T cells controls the growth of B16 melanoma in mice. Journal of Immunology, 184(8), 4215–4227. doi:10.4049/jimmunol.0902995.

146.

Muranski, P., Boni, A., Antony, P. A., Cassard, L., Irvine, K. R., Kaiser, A., et al. (2008). Tumor-specific Th17-polarized cells eradicate large established melanoma. Blood, 112(2), 362–373. doi:10.1182/blood-2007-11-120998.PubMed

147.

Miller, J. S., Soignier, Y., Panoskaltsis-Mortari, A., McNearney, S. A., Yun, G. H., Fautsch, S. K., et al. (2005). Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancer. Blood, 105(8), 3051–3057. doi:10.1182/blood-2004-07-2974.PubMed

148.

Pegram, H. J., Jackson, J. T., Smyth, M. J., Kershaw, M. H., & Darcy, P. K. (2008). Adoptive transfer of gene-modified primary NK cells can specifically inhibit tumor progression in vivo. Journal of Immunology, 181(5), 3449–3455.

Titel: How to improve the immunogenicity of chemotherapy and radiotherapy
verfasst von: Yuting Ma
Rosa Conforti
Laetitia Aymeric
Clara Locher
Oliver Kepp
Guido Kroemer
Laurence Zitvogel
Publikationsdatum: 01.03.2011
Verlag: Springer US
Erschienen in: Cancer and Metastasis Reviews / Ausgabe 1/2011
Print ISSN: 0167-7659
Elektronische ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-011-9283-2

Springer Medizin

How to improve the immunogenicity of chemotherapy and radiotherapy

Abstract

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Bei Senioren mit Prostatakarzinom auf Anämie achten!

ICI-Therapie in der Schwangerschaft wird gut toleriert

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Springer Medizin

Abstract

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