Abstract
Over the past decade, the ability of cancer cells to evade immune destruction has become recognized as one of the hallmarks of cancer. This understanding has paved the way for the development of novel therapeutic agents that can enhance activation of antitumor immune responses or reverse immunosuppressive mechanisms through which tumors escape immune-mediated rejection. The treatment of ovarian and breast cancers remains a therapeutic challenge, as these malignancies are often diagnosed in advanced stages, and many patients relapse despite appropriate management. Clinical trials have shown efficacy for various immunotherapeutic strategies, especially the use of tumor stroma-targeting antibodies; enhancement of tumor antigen presentation, such as with vaccines and toll-like receptor agonists; and the targeting of immunosuppressive mechanisms, via checkpoint blockade. Emerging preclinical and clinical data provide a strong rationale for combinatorial approaches in these malignancies.
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References
Hanahan D, Coussens LM. Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell. 2012;21(3):309–22.
Nienhuis HH, et al. Targeting breast cancer through its microenvironment: current status of preclinical and clinical research in finding relevant targets. Pharmacol Ther. 2015;147:63–79.
Bussard KM, Mutkus L, Stumpf K, Gomez-Manzano C, Marini FC. Tumor-associated stromal cells as key contributors to the tumor microenvironment. Breast Cancer Res. 2016;18(1):84.
Coventry BJ, Weightman MJ, Bradley J, Skinner JM. Immune profiling in human breast cancer using high-sensitivity detection and analysis techniques. JRSM Open. 2015;6(9):2054270415603909.
Salgado R, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an international TILs working group 2014. Ann Oncol. 2015;26(2):259–71.
Rody A, et al. A clinically relevant gene signature in triple-negative and basal-like breast cancer. Breast Cancer Res. 2011;13(5):R97.
Iwamoto T, et al. First generation prognostic gene signatures for breast cancer predict both survival and chemotherapy sensitivity and identify overlap** patient populations. Breast Cancer Res Treat. 2011;130(1):155–64.
Denkert C, et al. Strategies for develo** Ki67 as a useful biomarker in breast cancer. Breast. 2015;24(Suppl 2):S67–72.
Denkert C, et al. Tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy with or without carboplatin in human epidermal growth factor receptor 2-positive and triple-negative primary breast cancers. J Clin Oncol. 2015;33(9):983–91.
Loi S, et al. Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98. J Clin Oncol. 2013;31(7):860–7.
Adams S, et al. Prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol. 2014;32(27):2959–66.
Salgado R, et al. Tumor-infiltrating lymphocytes and associations with pathological complete response and event-free survival in HER2-positive early-stage breast cancer treated with lapatinib and trastuzumab: a secondary analysis of the NeoALTTO trial. JAMA Oncol. 2015;1(4):448–54.
Bianchini G, et al. Immune modulation of pathologic complete response after neoadjuvant HER2-directed therapies in the NeoSphere trial. Ann Oncol. 2015;26(12):2429–36.
Ma D, Gu MJ. Immune effect of tumor-infiltrating lymphocytes and its relation to the survival rate of patients with ovarian malignancies. J Tongji Med Univ. 1991;11(4):235–9.
Hwang WT, Adams SF, Tahirovic E, Hagemann IS, Coukos G. Prognostic significance of tumor-infiltrating T cells in ovarian cancer: a meta-analysis. Gynecol Oncol. 2012;124(2):192–8.
Paraiso KH, Smalley KS. Fibroblast-mediated drug resistance in cancer. Biochem Pharmacol. 2013;85(8):1033–41.
Liotta LA, Kohn EC. The microenvironment of the tumor-host interface. Nature. 2001;411(6835):375–9.
Kalluri R, Zeisberg M. Fibroblasts in cancer. Nat Rev Cancer. 2006;6(5):392–401.
Xouri G, Christian S. Origin and function of tumor stroma fibroblasts. Semin Cell Dev Biol. 2010;21(1):40–6.
Ibe S, Qin Z, Schuler T, Preiss S, Blankenstein T. Tumor rejection by disturbing tumor stroma cell interactions. J Exp Med. 2001;194(11):1549–59.
Lee J, Fassnacht M, Nair S, Boczkowski D, Gilboa E. Tumor immunotherapy targeting fibroblast activation protein, a product expressed in tumor-associated fibroblasts. Cancer Res. 2005;65(23):11156–63.
Pollard JW. Tumor-educated macrophages promote tumor progression and metastasis. Nat Rev Cancer. 2004;4(1):71–8.
Mantovani A, Sozzani S, Locati M, Allavena P, Sica A. Macrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytes. Trends Immunol. 2002;23(11):549–55.
DeNardo DG, et al. CD4(+) T cells regulate pulmonary metastasis of mammary carcinomas by enhancing protumor properties of macrophages. Cancer Cell. 2009;16(2):91–102.
Biswas SK, Mantovani A. Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol. 2010;11(10):889–96.
Lin EY, et al. Macrophages regulate the angiogenic switch in a mouse model of breast cancer. Cancer Res. 2006;66(23):11238–46.
Strachan DC, et al. CSF1R inhibition delays cervical and mammary tumor growth in murine models by attenuating the turnover of tumor-associated macrophages and enhancing infiltration by CD8+ T cells. Oncoimmunology. 2013;2(12):e26968.
DeNardo DG, et al. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discov. 2011;1(1):54–67.
Ries CH, et al. Targeting tumor-associated macrophages with anti-CSF-1R antibody reveals a strategy for cancer therapy. Cancer Cell. 2014;25(6):846–59.
Aghajanian C, et al. Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer. Gynecol Oncol. 2015;139(1):10–6.
Oza AM, et al. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol. 2015;16(8):928–36.
Patch AM, et al. Whole-genome characterization of chemoresistant ovarian cancer. Nature. 2015;521(7553):489–94.
Schumacher TN, Schreiber RD. Neoantigens in cancer immunotherapy. Science. 2015;348(6230):69–74.
Le DT, et al. PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med. 2015;372(26):2509–20.
Snyder A, et al. Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014;371(23):2189–99.
Cancer Genome Atlas Research Network. Integrated genomic analyses of ovarian carcinoma. Nature. 2011;474(7353):609–15.
Lee JM, Ledermann JA, Kohn EC. PARP inhibitors for BRCA1/2 mutation-associated and BRCA-like malignancies. Ann Oncol. 2014;25(1):32–40.
Ledermann J, et al. Olaparib maintenance therapy in patients with platinum-sensitive relapsed serous ovarian cancer: a preplanned retrospective analysis of outcomes by BRCA status in a randomised phase 2 trial. Lancet Oncol. 2014;15(8):852–61.
Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol. 2013;31:51–72.
Huang J, et al. The PARP1 inhibitor BMN 673 exhibits immunoregulatory effects in a Brca1(−/−) murine model of ovarian cancer. Biochem Biophys Res Commun. 2015;463(4):551–6.
Lu Y, Chu A, Turker MS, Glazer PM. Hypoxia-induced epigenetic regulation and silencing of the BRCA1 promoter. Mol Cell Biol. 2011;31(16):3339–50.
Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumors. Nat Rev Immunol. 2012;12(4):253–68.
Pujade-Lauraine E, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial. J Clin Oncol. 2014;32(13):1302–8.
Ledermann JA, et al. Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2016;387(10023):1066–74.
Zhang L, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003;348(3):203–13.
Sato E, et al. Intraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancer. Proc Natl Acad Sci U S A. 2005;102(51):18538–43.
Goodell V, et al. Antibody immunity to the p53 oncogenic protein is a prognostic indicator in ovarian cancer. J Clin Oncol. 2006;24(5):762–8.
Odunsi K, et al. Efficacy of vaccination with recombinant vaccinia and fowlpox vectors expressing NY-ESO-1 antigen in ovarian cancer and melanoma patients. Proc Natl Acad Sci U S A. 2012;109(15):5797–802.
Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell. 2010;140(6):805–20.
Zitvogel L, Galluzzi L, Kepp O, Smyth MJ, Kroemer G. Type I interferons in anticancer immunity. Nat Rev Immunol. 2015;15(7):405–14.
Alberts DS, et al. Randomized trial of adjuvant intraperitoneal alpha-interferon in stage III ovarian cancer patients who have no evidence of disease after primary surgery and chemotherapy: an intergroup study. Gynecol Oncol. 2006;100(1):133–8.
Kim KH, et al. A phase I clinical trial of Ad5/3-Delta24, a novel serotype-chimeric, infectivity-enhanced, conditionally-replicative adenovirus (CRAd), in patients with recurrent ovarian cancer. Gynecol Oncol. 2013;130(3):518–24.
Edwards RP, et al. Comparison of toxicity and survival following intraperitoneal recombinant interleukin-2 for persistent ovarian cancer after platinum: twenty-four-hour versus 7-day infusion. J Clin Oncol. 1997;15(11):3399–407.
Alvarez RD, et al. A phase II trial of intraperitoneal EGEN-001, an IL-12 plasmid formulated with PEG-PEI-cholesterol lipopolymer in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal cancer: a gynecologic oncology group study. Gynecol Oncol. 2014;133(3):433–8.
Chen DS, Mellman I. Oncology meets immunology: the cancer-immunity cycle. Immunity. 2013;39(1):1–10.
Hodi FS, et al. 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. 2008;105(8):3005–10.
Hamanishi J, et al. Safety and antitumor activity of anti-PD-1 antibody, nivolumab, in patients with platinum-resistant ovarian cancer. J Clin Oncol. 2015;33(34):4015–22.
Larkin J, Hodi FS, Wolchok JD. Combined Nivolumab and Ipilimumab or monotherapy in untreated melanoma. N Engl J Med. 2015;373(13):1270–1.
Fujita K, et al. Prolonged disease-free period in patients with advanced epithelial ovarian cancer after adoptive transfer of tumor-infiltrating lymphocytes. Clin Cancer Res. 1995;1(5):501–7.
Chekmasova AA, et al. Successful eradication of established peritoneal ovarian tumors in SCID-beige mice following adoptive transfer of T cells genetically targeted to the MUC16 antigen. Clin Cancer Res. 2010;16(14):3594–606.
Kelemen LE, et al. Consortium analysis of gene and gene-folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk. Mol Nutr Food Res. 2014;58(10):2023–35.
Inaba T, et al. Role of the immunosuppressive enzyme indoleamine 2,3-dioxygenase in the progression of ovarian carcinoma. Gynecol Oncol. 2009;115(2):185–92.
Gray JC, et al. Optimising anti-tumor CD8 T-cell responses using combinations of immunomodulatory antibodies. Eur J Immunol. 2008;38(9):2499–511.
Mittendorf EA, et al. Final report of the phase I/II clinical trial of the E75 (nelipepimut-S) vaccine with booster inoculations to prevent disease recurrence in high-risk breast cancer patients. Ann Oncol. 2014;25(9):1735–42.
Rugo HS S Publication Number: S5-07 Preliminary efficacy and safety of pembrolizumab (MK-3475) in patients with PD-L1–positive, estrogen receptor-positive(ER+)/HER2-negative advanced breast cancer enrolled in KEYNOTE-028. 2015 San Antonio Breast Cancer Symposium doi:10.1158/1538-7445.SABCS15-S5-07.
S Tolaney, C Savulsky, G Aktan, D **ng, A Almonte, V Karantza and S Diab Cancer Res. 2017;77 (4):P5-15-02–P5-15-02. doi:10.1158/1538-7445.SABCS16-P5-15-02.
Nanda R, et al. Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib KEYNOTE-012 study. J Clin Oncol. 2016;34(21):2460–7.
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Saint-Ghislain, M., Bretagne, M., Sablin, MP., Romano, E. (2018). Challenges of Oncoimmunology for Ovarian and Breast Cancers. In: Zitvogel, L., Kroemer, G. (eds) Oncoimmunology. Springer, Cham. https://doi.org/10.1007/978-3-319-62431-0_36
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