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Erschienen in: Die Gynäkologie 8/2022

14.07.2022 | Ovarialkarzinom | Gynäkologie aktuell

Ovarialkarzinom: Immuntherapie, quo vadis?

verfasst von: Prof. Dr. Frederik Marmé

Erschienen in: Die Gynäkologie | Ausgabe 8/2022

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Die Einführung der Immuntherapie hat in der Therapie vieler solider Tumoren zu einem Paradigmenwechsel geführt. …
Literatur
1.
Zurück zum Zitat Zhang L, Conejo-Garcia JR, Katsaros D et al (2003) Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 348:203–213 PubMedCrossRef Zhang L, Conejo-Garcia JR, Katsaros D et al (2003) Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med 348:203–213 PubMedCrossRef
2.
Zurück zum Zitat Hwang WT, Adams SF, Tahirovic E et al (2012) Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis. Gynecol Oncol 124:192–198 PubMedCrossRef Hwang WT, Adams SF, Tahirovic E et al (2012) Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis. Gynecol Oncol 124:192–198 PubMedCrossRef
3.
Zurück zum Zitat Ovarian Tumor Tissue Analysis C, Goode EL, Block MS et al (2017) Dose-response association of CD8+ tumor-infiltrating lymphocytes and survival time in high-grade serous ovarian cancer. JAMA Oncol 3:e173290 CrossRef Ovarian Tumor Tissue Analysis C, Goode EL, Block MS et al (2017) Dose-response association of CD8+ tumor-infiltrating lymphocytes and survival time in high-grade serous ovarian cancer. JAMA Oncol 3:e173290 CrossRef
4.
Zurück zum Zitat Zhang QW, Liu L, Gong CY et al (2012) Prognostic significance of tumor-associated macrophages in solid tumor: a meta-analysis of the literature. PLoS One 7:e50946 PubMedPubMedCentralCrossRef Zhang QW, Liu L, Gong CY et al (2012) Prognostic significance of tumor-associated macrophages in solid tumor: a meta-analysis of the literature. PLoS One 7:e50946 PubMedPubMedCentralCrossRef
5.
Zurück zum Zitat Wolf D, Wolf AM, Rumpold H et al (2005) The expression of the regulatory T cell-specific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer. Clin Cancer Res 11:8326–8331 PubMedCrossRef Wolf D, Wolf AM, Rumpold H et al (2005) The expression of the regulatory T cell-specific forkhead box transcription factor FoxP3 is associated with poor prognosis in ovarian cancer. Clin Cancer Res 11:8326–8331 PubMedCrossRef
6.
Zurück zum Zitat Wei S, Kryczek I, Zou L et al (2005) Plasmacytoid dendritic cells induce CD8+ regulatory T cells in human ovarian carcinoma. Cancer Res 65:5020–5026 PubMedCrossRef Wei S, Kryczek I, Zou L et al (2005) Plasmacytoid dendritic cells induce CD8+ regulatory T cells in human ovarian carcinoma. Cancer Res 65:5020–5026 PubMedCrossRef
7.
Zurück zum Zitat Redjimi N, Raffin C, Raimbaud I et al (2012) CXCR3+ T regulatory cells selectively accumulate in human ovarian carcinomas to limit type I immunity. Cancer Res 72:4351–4360 PubMedCrossRef Redjimi N, Raffin C, Raimbaud I et al (2012) CXCR3+ T regulatory cells selectively accumulate in human ovarian carcinomas to limit type I immunity. Cancer Res 72:4351–4360 PubMedCrossRef
8.
Zurück zum Zitat Labidi-Galy SI, Sisirak V, Meeus P et al (2011) Quantitative and functional alterations of plasmacytoid dendritic cells contribute to immune tolerance in ovarian cancer. Cancer Res 71:5423–5434 PubMedCrossRef Labidi-Galy SI, Sisirak V, Meeus P et al (2011) Quantitative and functional alterations of plasmacytoid dendritic cells contribute to immune tolerance in ovarian cancer. Cancer Res 71:5423–5434 PubMedCrossRef
9.
Zurück zum Zitat Kryczek I, Wei S, Zhu G et al (2007) Relationship between B7-H4, regulatory T cells, and patient outcome in human ovarian carcinoma. Cancer Res 67:8900–8905 PubMedCrossRef Kryczek I, Wei S, Zhu G et al (2007) Relationship between B7-H4, regulatory T cells, and patient outcome in human ovarian carcinoma. Cancer Res 67:8900–8905 PubMedCrossRef
10.
Zurück zum Zitat Curiel TJ, Coukos G, Zou L et al (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942–949 PubMedCrossRef Curiel TJ, Coukos G, Zou L et al (2004) Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival. Nat Med 10:942–949 PubMedCrossRef
11.
Zurück zum Zitat Baert T, Vankerckhoven A, Riva M et al (2019) Myeloid derived suppressor cells: key drivers of immunosuppression in ovarian cancer. Front Immunol 10:1273 PubMedPubMedCentralCrossRef Baert T, Vankerckhoven A, Riva M et al (2019) Myeloid derived suppressor cells: key drivers of immunosuppression in ovarian cancer. Front Immunol 10:1273 PubMedPubMedCentralCrossRef
12.
Zurück zum Zitat Schumacher TN, Schreiber RD (2015) Neoantigens in cancer immunotherapy. Science 348:69–74 PubMedCrossRef Schumacher TN, Schreiber RD (2015) Neoantigens in cancer immunotherapy. Science 348:69–74 PubMedCrossRef
13.
Zurück zum Zitat Hacohen N, Fritsch EF, Carter TA et al (2013) Getting personal with neoantigen-based therapeutic cancer vaccines. Cancer Immunol Res 1:11–15 PubMedPubMedCentralCrossRef Hacohen N, Fritsch EF, Carter TA et al (2013) Getting personal with neoantigen-based therapeutic cancer vaccines. Cancer Immunol Res 1:11–15 PubMedPubMedCentralCrossRef
14.
Zurück zum Zitat Chen DS, Mellman I (2017) Elements of cancer immunity and the cancer-immune set point. Nature 541:321–330 PubMedCrossRef Chen DS, Mellman I (2017) Elements of cancer immunity and the cancer-immune set point. Nature 541:321–330 PubMedCrossRef
15.
Zurück zum Zitat Schumacher TN, Hacohen N (2016) Neoantigens encoded in the cancer genome. Curr Opin Immunol 41:98–103 PubMedCrossRef Schumacher TN, Hacohen N (2016) Neoantigens encoded in the cancer genome. Curr Opin Immunol 41:98–103 PubMedCrossRef
16.
Zurück zum Zitat Turajlic S, Litchfield K, Xu H et al (2017) Insertion-and-deletion-derived tumour-specific neoantigens and the immunogenic phenotype: a pan-cancer analysis. Lancet Oncol 18:1009–1021 PubMedCrossRef Turajlic S, Litchfield K, Xu H et al (2017) Insertion-and-deletion-derived tumour-specific neoantigens and the immunogenic phenotype: a pan-cancer analysis. Lancet Oncol 18:1009–1021 PubMedCrossRef
18.
Zurück zum Zitat Petrelli F, Ghidini M, Ghidini A, Tomasello G (2020) Outcomes following immune checkpoint inhibitor treatment of patients with microsatellite instability-high cancers: a systematic review and meta-analysis. JAMA Oncol 6:1068–1071 PubMedCrossRef Petrelli F, Ghidini M, Ghidini A, Tomasello G (2020) Outcomes following immune checkpoint inhibitor treatment of patients with microsatellite instability-high cancers: a systematic review and meta-analysis. JAMA Oncol 6:1068–1071 PubMedCrossRef
21.
Zurück zum Zitat Le DT, Durham JN, Smith KN et al (2017) Mismatch repair deficiency predicts response of solid tumors to PD‑1 blockade. Science 357:409–413 PubMedPubMedCentralCrossRef Le DT, Durham JN, Smith KN et al (2017) Mismatch repair deficiency predicts response of solid tumors to PD‑1 blockade. Science 357:409–413 PubMedPubMedCentralCrossRef
22.
23.
Zurück zum Zitat Samstein RM, Lee CH, Shoushtari AN et al (2019) Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet 51:202–206 PubMedPubMedCentralCrossRef Samstein RM, Lee CH, Shoushtari AN et al (2019) Tumor mutational load predicts survival after immunotherapy across multiple cancer types. Nat Genet 51:202–206 PubMedPubMedCentralCrossRef
24.
Zurück zum Zitat Marabelle A, Fakih M, Lopez J et al (2020) Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol 21:1353–1365 PubMedCrossRef Marabelle A, Fakih M, Lopez J et al (2020) Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol 21:1353–1365 PubMedCrossRef
25.
Zurück zum Zitat Cancer Genome Atlas Research Network (2011) Integrated genomic analyses of ovarian carcinoma. Nature 474:609–615 CrossRef Cancer Genome Atlas Research Network (2011) Integrated genomic analyses of ovarian carcinoma. Nature 474:609–615 CrossRef
26.
Zurück zum Zitat Konstantinopoulos PA, Ceccaldi R, Shapiro GI, D’Andrea AD (2015) Homologous recombination deficiency: exploiting the fundamental vulnerability of ovarian cancer. Cancer Discov 5:1137–1154 PubMedPubMedCentralCrossRef Konstantinopoulos PA, Ceccaldi R, Shapiro GI, D’Andrea AD (2015) Homologous recombination deficiency: exploiting the fundamental vulnerability of ovarian cancer. Cancer Discov 5:1137–1154 PubMedPubMedCentralCrossRef
27.
Zurück zum Zitat Zehir A, Benayed R, Shah RH et al (2017) Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med 23:703–713 PubMedPubMedCentralCrossRef Zehir A, Benayed R, Shah RH et al (2017) Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med 23:703–713 PubMedPubMedCentralCrossRef
28.
Zurück zum Zitat Chalmers ZR, Connelly CF, Fabrizio D et al (2017) Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med 9:34 PubMedPubMedCentralCrossRef Chalmers ZR, Connelly CF, Fabrizio D et al (2017) Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden. Genome Med 9:34 PubMedPubMedCentralCrossRef
29.
Zurück zum Zitat Hauke J, Hahnen E, Schneider S et al (2019) Deleterious somatic variants in 473 consecutive individuals with ovarian cancer: results of the observational AGO-TR1 study (NCT02222883). J Med Genet 56:574–580 PubMedCrossRef Hauke J, Hahnen E, Schneider S et al (2019) Deleterious somatic variants in 473 consecutive individuals with ovarian cancer: results of the observational AGO-TR1 study (NCT02222883). J Med Genet 56:574–580 PubMedCrossRef
30.
Zurück zum Zitat Harter P, Hauke J, Heitz F et al (2017) Prevalence of deleterious germline variants in risk genes including BRCA1/2 in consecutive ovarian cancer patients (AGO-TR-1). PLoS ONE 12:e186043 PubMedPubMedCentralCrossRef Harter P, Hauke J, Heitz F et al (2017) Prevalence of deleterious germline variants in risk genes including BRCA1/2 in consecutive ovarian cancer patients (AGO-TR-1). PLoS ONE 12:e186043 PubMedPubMedCentralCrossRef
32.
Zurück zum Zitat Hodi FS, Butler M, Oble DA et al (2008) Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients. Proc Natl Acad Sci U S A 105:3005–3010 PubMedPubMedCentralCrossRef Hodi FS, Butler M, Oble DA et al (2008) Immunologic and clinical effects of antibody blockade of cytotoxic T lymphocyte-associated antigen 4 in previously vaccinated cancer patients. Proc Natl Acad Sci U S A 105:3005–3010 PubMedPubMedCentralCrossRef
33.
Zurück zum Zitat Hodi FS, Mihm MC, Soiffer RJ et al (2003) Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc Natl Acad Sci U S A 100:4712–4717 PubMedPubMedCentralCrossRef Hodi FS, Mihm MC, Soiffer RJ et al (2003) Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc Natl Acad Sci U S A 100:4712–4717 PubMedPubMedCentralCrossRef
35.
Zurück zum Zitat Varga A, Piha-Paul S, Ott PA et al (2019) Pembrolizumab in patients with programmed death ligand 1‑positive advanced ovarian cancer: analysis of KEYNOTE-028. Gynecol Oncol 152:243–250 PubMedCrossRef Varga A, Piha-Paul S, Ott PA et al (2019) Pembrolizumab in patients with programmed death ligand 1‑positive advanced ovarian cancer: analysis of KEYNOTE-028. Gynecol Oncol 152:243–250 PubMedCrossRef
36.
Zurück zum Zitat Disis ML, Taylor MH, Kelly K et al (2019) Efficacy and safety of avelumab for patients with recurrent or refractory ovarian cancer: phase 1b results from the JAVELIN solid tumor trial. JAMA Oncol 5(3):393–401 PubMedPubMedCentralCrossRef Disis ML, Taylor MH, Kelly K et al (2019) Efficacy and safety of avelumab for patients with recurrent or refractory ovarian cancer: phase 1b results from the JAVELIN solid tumor trial. JAMA Oncol 5(3):393–401 PubMedPubMedCentralCrossRef
37.
Zurück zum Zitat Matulonis UA (2020) Final results from the KEYNOTE-100 trial of pembrolizumab in patients with advanced recurrent ovarian cancer. In: Matulonis UA et al (Hrsg) ASCO virtual scientific program. American Society of Clinical Oncology, Matulonis UA (2020) Final results from the KEYNOTE-100 trial of pembrolizumab in patients with advanced recurrent ovarian cancer. In: Matulonis UA et al (Hrsg) ASCO virtual scientific program. American Society of Clinical Oncology,
38.
Zurück zum Zitat Ledermann JA, Shapira-Frommer R, Santin AD et al (2020) 843P association of gene expression signatures and TMB with response to pembrolizumab (pembro) in patients (pts) with recurrent ovarian cancer (ROC) enrolled in KEYNOTE-100. Ann Oncol 31:S631–S632 CrossRef Ledermann JA, Shapira-Frommer R, Santin AD et al (2020) 843P association of gene expression signatures and TMB with response to pembrolizumab (pembro) in patients (pts) with recurrent ovarian cancer (ROC) enrolled in KEYNOTE-100. Ann Oncol 31:S631–S632 CrossRef
39.
Zurück zum Zitat Matulonis UA, Shapira-Frommer R, Santin AD et al (2019) Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study. Ann Oncol 30:1080–1087 PubMedCrossRef Matulonis UA, Shapira-Frommer R, Santin AD et al (2019) Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study. Ann Oncol 30:1080–1087 PubMedCrossRef
40.
Zurück zum Zitat Matulonis UA, Shapira-Frommer R, Santin A et al (2018) Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: Interim results from the phase 2 KEYNOTE-100 study. J Clin Oncol 36:5511–5511 CrossRef Matulonis UA, Shapira-Frommer R, Santin A et al (2018) Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: Interim results from the phase 2 KEYNOTE-100 study. J Clin Oncol 36:5511–5511 CrossRef
41.
Zurück zum Zitat Ledermann JA, Shapira-Frommer R, Santin A et al (2018) Association of PD-L1 expression and gene expression profiling with clinical response to pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study. Ann Oncol 29:viii728 CrossRef Ledermann JA, Shapira-Frommer R, Santin A et al (2018) Association of PD-L1 expression and gene expression profiling with clinical response to pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study. Ann Oncol 29:viii728 CrossRef
42.
Zurück zum Zitat Hamanishi J, Takeshima N, Katsumata N et al (2021) Nivolumab versus gemcitabine or pegylated liposomal doxorubicin for patients with platinum-resistant ovarian cancer: open-label, randomized trial in Japan (NINJA). J Clin Oncol 39:3671–3681 PubMedCrossRef Hamanishi J, Takeshima N, Katsumata N et al (2021) Nivolumab versus gemcitabine or pegylated liposomal doxorubicin for patients with platinum-resistant ovarian cancer: open-label, randomized trial in Japan (NINJA). J Clin Oncol 39:3671–3681 PubMedCrossRef
43.
Zurück zum Zitat Kroemer G, Galluzzi L, Kepp O, Zitvogel L (2013) Immunogenic cell death in cancer therapy. Annu Rev Immunol 31:51–72 PubMedCrossRef Kroemer G, Galluzzi L, Kepp O, Zitvogel L (2013) Immunogenic cell death in cancer therapy. Annu Rev Immunol 31:51–72 PubMedCrossRef
44.
Zurück zum Zitat Zitvogel L, Kepp O, Kroemer G (2011) Immune parameters affecting the efficacy of chemotherapeutic regimens. Nat Rev Clin Oncol 8:151–160 PubMedCrossRef Zitvogel L, Kepp O, Kroemer G (2011) Immune parameters affecting the efficacy of chemotherapeutic regimens. Nat Rev Clin Oncol 8:151–160 PubMedCrossRef
45.
Zurück zum Zitat Denkert C, Loibl S, Noske A et al (2010) Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol 28:105–113 PubMedCrossRef Denkert C, Loibl S, Noske A et al (2010) Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol 28:105–113 PubMedCrossRef
46.
Zurück zum Zitat Sistigu A, Yamazaki T, Vacchelli E et al (2014) Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy. Nat Med 20:1301–1309 PubMedCrossRef Sistigu A, Yamazaki T, Vacchelli E et al (2014) Cancer cell-autonomous contribution of type I interferon signaling to the efficacy of chemotherapy. Nat Med 20:1301–1309 PubMedCrossRef
47.
Zurück zum Zitat Alizadeh D, Trad M, Hanke NT et al (2014) Doxorubicin eliminates myeloid-derived suppressor cells and enhances the efficacy of adoptive T‑cell transfer in breast cancer. Cancer Res 74:104–118 PubMedCrossRef Alizadeh D, Trad M, Hanke NT et al (2014) Doxorubicin eliminates myeloid-derived suppressor cells and enhances the efficacy of adoptive T‑cell transfer in breast cancer. Cancer Res 74:104–118 PubMedCrossRef
48.
Zurück zum Zitat Pujade-Lauraine E, Fujiwara K, Ledermann JA et al (2021) Avelumab alone or in combination with chemotherapy versus chemotherapy alone in platinum-resistant or platinum-refractory ovarian cancer (JAVELIN Ovarian 200): an open-label, three-arm, randomised, phase 3 study. Lancet Oncol 22:1034–1046 PubMedCrossRef Pujade-Lauraine E, Fujiwara K, Ledermann JA et al (2021) Avelumab alone or in combination with chemotherapy versus chemotherapy alone in platinum-resistant or platinum-refractory ovarian cancer (JAVELIN Ovarian 200): an open-label, three-arm, randomised, phase 3 study. Lancet Oncol 22:1034–1046 PubMedCrossRef
49.
Zurück zum Zitat Monk BJ, Colombo N, Oza AM et al (2021) Chemotherapy with or without avelumab followed by avelumab maintenance versus chemotherapy alone in patients with previously untreated epithelial ovarian cancer (JAVELIN Ovarian 100): an open-label, randomised, phase 3 trial. Lancet Oncol 22:1275–1289 PubMedCrossRef Monk BJ, Colombo N, Oza AM et al (2021) Chemotherapy with or without avelumab followed by avelumab maintenance versus chemotherapy alone in patients with previously untreated epithelial ovarian cancer (JAVELIN Ovarian 100): an open-label, randomised, phase 3 trial. Lancet Oncol 22:1275–1289 PubMedCrossRef
51.
Zurück zum Zitat Voron T, Colussi O, Marcheteau E et al (2015) VEGF‑A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors. J Exp Med 212:139–148 PubMedPubMedCentralCrossRef Voron T, Colussi O, Marcheteau E et al (2015) VEGF‑A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors. J Exp Med 212:139–148 PubMedPubMedCentralCrossRef
52.
Zurück zum Zitat Gavalas NG, Tsiatas M, Tsitsilonis O et al (2012) VEGF directly suppresses activation of T cells from ascites secondary to ovarian cancer via VEGF receptor type 2. Br J Cancer 107:1869–1875 PubMedPubMedCentralCrossRef Gavalas NG, Tsiatas M, Tsitsilonis O et al (2012) VEGF directly suppresses activation of T cells from ascites secondary to ovarian cancer via VEGF receptor type 2. Br J Cancer 107:1869–1875 PubMedPubMedCentralCrossRef
53.
Zurück zum Zitat Terme M, Pernot S, Marcheteau E et al (2013) VEGFA-VEGFR pathway blockade inhibits tumor-induced regulatory T‑cell proliferation in colorectal cancer. Cancer Res 73:539–549 PubMedCrossRef Terme M, Pernot S, Marcheteau E et al (2013) VEGFA-VEGFR pathway blockade inhibits tumor-induced regulatory T‑cell proliferation in colorectal cancer. Cancer Res 73:539–549 PubMedCrossRef
54.
Zurück zum Zitat Motz GT, Santoro SP, Wang LP et al (2014) Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors. Nat Med 20:607–615 PubMedPubMedCentralCrossRef Motz GT, Santoro SP, Wang LP et al (2014) Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors. Nat Med 20:607–615 PubMedPubMedCentralCrossRef
55.
Zurück zum Zitat Buckanovich RJ, Facciabene A, Kim S et al (2008) Endothelin B receptor mediates the endothelial barrier to T cell homing to tumors and disables immune therapy. Nat Med 14:28–36 PubMedCrossRef Buckanovich RJ, Facciabene A, Kim S et al (2008) Endothelin B receptor mediates the endothelial barrier to T cell homing to tumors and disables immune therapy. Nat Med 14:28–36 PubMedCrossRef
56.
Zurück zum Zitat Bouzin C, Brouet A, De Vriese J et al (2007) Effects of vascular endothelial growth factor on the lymphocyte-endothelium interactions: identification of caveolin‑1 and nitric oxide as control points of endothelial cell anergy. J Immunol 178:1505–1511 PubMedCrossRef Bouzin C, Brouet A, De Vriese J et al (2007) Effects of vascular endothelial growth factor on the lymphocyte-endothelium interactions: identification of caveolin‑1 and nitric oxide as control points of endothelial cell anergy. J Immunol 178:1505–1511 PubMedCrossRef
57.
Zurück zum Zitat Shrimali RK, Yu Z, Theoret MR et al (2010) Antiangiogenic agents can increase lymphocyte infiltration into tumor and enhance the effectiveness of adoptive immunotherapy of cancer. Cancer Res 70:6171–6180 PubMedPubMedCentralCrossRef Shrimali RK, Yu Z, Theoret MR et al (2010) Antiangiogenic agents can increase lymphocyte infiltration into tumor and enhance the effectiveness of adoptive immunotherapy of cancer. Cancer Res 70:6171–6180 PubMedPubMedCentralCrossRef
58.
Zurück zum Zitat Wallin JJ, Bendell JC, Funke R et al (2016) Atezolizumab in combination with bevacizumab enhances antigen-specific T‑cell migration in metastatic renal cell carcinoma. Nat Commun 7:12624 PubMedPubMedCentralCrossRef Wallin JJ, Bendell JC, Funke R et al (2016) Atezolizumab in combination with bevacizumab enhances antigen-specific T‑cell migration in metastatic renal cell carcinoma. Nat Commun 7:12624 PubMedPubMedCentralCrossRef
59.
Zurück zum Zitat Liu JF, Herold C, Gray KP et al (2019) Assessment of combined nivolumab and bevacizumab in relapsed ovarian cancer: a phase 2 clinical trial. JAMA Oncol 5:1731–1738 PubMedPubMedCentralCrossRef Liu JF, Herold C, Gray KP et al (2019) Assessment of combined nivolumab and bevacizumab in relapsed ovarian cancer: a phase 2 clinical trial. JAMA Oncol 5:1731–1738 PubMedPubMedCentralCrossRef
60.
Zurück zum Zitat Moore KN, Bookman M, Sehouli J et al (2021) Atezolizumab, bevacizumab, and chemotherapy for newly diagnosed stage III or IV ovarian cancer: placebo-controlled randomized phase III trial (IMagyn050/GOG 3015/ENGOT-OV39). J Clin Oncol 39:1842–1855 PubMedPubMedCentralCrossRef Moore KN, Bookman M, Sehouli J et al (2021) Atezolizumab, bevacizumab, and chemotherapy for newly diagnosed stage III or IV ovarian cancer: placebo-controlled randomized phase III trial (IMagyn050/GOG 3015/ENGOT-OV39). J Clin Oncol 39:1842–1855 PubMedPubMedCentralCrossRef
61.
Zurück zum Zitat Landen C, Molinero L, Sehouli J et al (2021) Association of BRCA1/2, homologous recombination deficiency, and PD-L1 with clinical outcomes in patients receiving atezolizumab versus placebo combined with carboplatin, paclitaxel, and bevacizumab for newly diagnosed ovarian cancer: exploratory analyses of IMagyn050/GOG3015/ENGOT-ov39. Gynecol Oncol 162:S37–S38 CrossRef Landen C, Molinero L, Sehouli J et al (2021) Association of BRCA1/2, homologous recombination deficiency, and PD-L1 with clinical outcomes in patients receiving atezolizumab versus placebo combined with carboplatin, paclitaxel, and bevacizumab for newly diagnosed ovarian cancer: exploratory analyses of IMagyn050/GOG3015/ENGOT-ov39. Gynecol Oncol 162:S37–S38 CrossRef
62.
Zurück zum Zitat Kurtz JE, Marth C, Oaknin A et al (2018) ATALANTE (ENGOT-ov29): a randomized, double-blinded, phase III study of atezolizumab versus placebo in patients with late relapse of epithelial ovarian, fallopian tube, or peritoneal cancer treated by platinum-based chemotherapy and bevacizumab. J Clin Oncol 36:TPS5607 CrossRef Kurtz JE, Marth C, Oaknin A et al (2018) ATALANTE (ENGOT-ov29): a randomized, double-blinded, phase III study of atezolizumab versus placebo in patients with late relapse of epithelial ovarian, fallopian tube, or peritoneal cancer treated by platinum-based chemotherapy and bevacizumab. J Clin Oncol 36:TPS5607 CrossRef
63.
Zurück zum Zitat Harter P, Pautier P, Van Nieuwenhuysen E et al (2020) Atezolizumab in combination with bevacizumab and chemotherapy versus bevacizumab and chemotherapy in recurrent ovarian cancer—a randomized phase III trial (AGO-OVAR 2.29/ENGOT-ov34). Int J Gynecol Cancer 30:1997–2001 PubMedCrossRef Harter P, Pautier P, Van Nieuwenhuysen E et al (2020) Atezolizumab in combination with bevacizumab and chemotherapy versus bevacizumab and chemotherapy in recurrent ovarian cancer—a randomized phase III trial (AGO-OVAR 2.29/ENGOT-ov34). Int J Gynecol Cancer 30:1997–2001 PubMedCrossRef
64.
Zurück zum Zitat Stewart RA, Pilié PG, Yap TA (2018) Development of PARP and immune-checkpoint inhibitor combinations. Cancer Res 78:6717–6725 PubMedCrossRef Stewart RA, Pilié PG, Yap TA (2018) Development of PARP and immune-checkpoint inhibitor combinations. Cancer Res 78:6717–6725 PubMedCrossRef
65.
Zurück zum Zitat Huang J, Wang L, Cong Z et al (2015) The PARP1 inhibitor BMN 673 exhibits immunoregulatory effects in a Brca1(−/−) murine model of ovarian cancer. Biochem Biophys Res Commun 463:551–556 PubMedCrossRef Huang J, Wang L, Cong Z et al (2015) The PARP1 inhibitor BMN 673 exhibits immunoregulatory effects in a Brca1(−/−) murine model of ovarian cancer. Biochem Biophys Res Commun 463:551–556 PubMedCrossRef
66.
Zurück zum Zitat Shen J, Zhao W, Ju Z et al (2018) PARPi triggers STING-dependent immune response and enhances therapeutic efficacy of immune checkpoint blockade independent of BRCAness (bioRxiv) CrossRef Shen J, Zhao W, Ju Z et al (2018) PARPi triggers STING-dependent immune response and enhances therapeutic efficacy of immune checkpoint blockade independent of BRCAness (bioRxiv) CrossRef
67.
Zurück zum Zitat Jiao S, Xia W, Yamaguchi H et al (2017) PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression. Clin Cancer Res 23:3711–3720 PubMedPubMedCentralCrossRef Jiao S, Xia W, Yamaguchi H et al (2017) PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression. Clin Cancer Res 23:3711–3720 PubMedPubMedCentralCrossRef
68.
Zurück zum Zitat Garcia-Diaz A, Shin DS, Moreno BH et al (2017) Interferon receptor signaling pathways regulating PD-L1 and PD-L2 expression. Cell Rep 19:1189–1201 PubMedPubMedCentralCrossRef Garcia-Diaz A, Shin DS, Moreno BH et al (2017) Interferon receptor signaling pathways regulating PD-L1 and PD-L2 expression. Cell Rep 19:1189–1201 PubMedPubMedCentralCrossRef
69.
Zurück zum Zitat Robillard L, Nguyen M, Loehr A et al (2017) Abstract 3650: preclinical evaluation of the PARP inhibitor rucaparib in combination with PD‑1 and PD-L1 inhibition in a syngeneic BRCA1 mutant ovarian cancer model. Cancer Res 77:3650 CrossRef Robillard L, Nguyen M, Loehr A et al (2017) Abstract 3650: preclinical evaluation of the PARP inhibitor rucaparib in combination with PD‑1 and PD-L1 inhibition in a syngeneic BRCA1 mutant ovarian cancer model. Cancer Res 77:3650 CrossRef
71.
Zurück zum Zitat Drew Y, Kaufman B, Banerjee S et al (2019) Phase II study of olaparib + durvalumab (MEDIOLA): updated results in germline BRCA-mutated platinum-sensitive relapsed (PSR) ovarian cancer (OC). Ann Oncol 30:v485–v486 CrossRef Drew Y, Kaufman B, Banerjee S et al (2019) Phase II study of olaparib + durvalumab (MEDIOLA): updated results in germline BRCA-mutated platinum-sensitive relapsed (PSR) ovarian cancer (OC). Ann Oncol 30:v485–v486 CrossRef
72.
Zurück zum Zitat Drew Y, Penson RT, O’Malley DM et al (2020) 814MO phase II study of olaparib (O) plus durvalumab (D) and bevacizumab (B) (MEDIOLA): initial results in patients (pts) with non-germline BRCA-mutated (non-gBRCAm) platinum sensitive relapsed (PSR) ovarian cancer (OC). Ann Oncol 31:S615–S616 CrossRef Drew Y, Penson RT, O’Malley DM et al (2020) 814MO phase II study of olaparib (O) plus durvalumab (D) and bevacizumab (B) (MEDIOLA): initial results in patients (pts) with non-germline BRCA-mutated (non-gBRCAm) platinum sensitive relapsed (PSR) ovarian cancer (OC). Ann Oncol 31:S615–S616 CrossRef
73.
Zurück zum Zitat Larkin J, Chiarion-Sileni V, Gonzalez R et al (2019) Five-year survival with combined nivolumab and Ipilimumab in advanced melanoma. N Engl J Med 381:1535–1546 PubMedCrossRef Larkin J, Chiarion-Sileni V, Gonzalez R et al (2019) Five-year survival with combined nivolumab and Ipilimumab in advanced melanoma. N Engl J Med 381:1535–1546 PubMedCrossRef
74.
Zurück zum Zitat Hinchcliff E, Patel A, Fellman B et al (2021) Randomized phase II trial of durvalumab (anti-PDL1) and tremelimumab (anti-CTLA4) administered in combination versus sequentially for the treatment of recurrent platinum-resistant non-clear cell ovarian cancer (NCT03026062). Gynecol Oncol 162:S39 CrossRef Hinchcliff E, Patel A, Fellman B et al (2021) Randomized phase II trial of durvalumab (anti-PDL1) and tremelimumab (anti-CTLA4) administered in combination versus sequentially for the treatment of recurrent platinum-resistant non-clear cell ovarian cancer (NCT03026062). Gynecol Oncol 162:S39 CrossRef
75.
Zurück zum Zitat Weber JS, Hodi FS, Wolchok JD et al (2017) Safety profile of nivolumab monotherapy: a pooled analysis of patients with advanced melanoma. J Clin Oncol 35:785–792 PubMedCrossRef Weber JS, Hodi FS, Wolchok JD et al (2017) Safety profile of nivolumab monotherapy: a pooled analysis of patients with advanced melanoma. J Clin Oncol 35:785–792 PubMedCrossRef
Metadaten
Titel
Ovarialkarzinom: Immuntherapie, quo vadis?
verfasst von
Prof. Dr. Frederik Marmé
Publikationsdatum
14.07.2022
Verlag
Springer Medizin
Erschienen in
Die Gynäkologie / Ausgabe 8/2022
Print ISSN: 2731-7102
Elektronische ISSN: 2731-7110
DOI
https://doi.org/10.1007/s00129-022-04963-0

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