Breast cancer genomics and immuno-oncological markers to guide immune therapies

Seminars in Cancer Biology

Volumn 52, Issue , 2018, Pages 178-188

  Hammerl, D ^a   Smid, M ^a   Timmermans, A M ^a   Sleijfer, S ^a   Martens, J W M ^a   Debets, R ^a  

^a ERASMUS MC CANCER INSTITUTE   (Netherlands)

Author keywords

Antigens; Breast cancer; Immune evasive mechanisms; Immune oncological markers; Immunotherapy; TILs

Indexed keywords

BIOLOGICAL MARKER; IMMUNO ONCOLOGICAL MARKER; UNCLASSIFIED DRUG; TUMOR MARKER;

ANTIGEN PRESENTATION; BREAST CANCER; BREAST TISSUE; CANCER IMMUNOTHERAPY; CANCER PROGNOSIS; CELLS; CLINICAL OUTCOME; ESTROGEN RECEPTOR NEGATIVE BREAST CANCER; ESTROGEN RECEPTOR POSITIVE BREAST CANCER; GENOMICS; HUMAN; IMMUNE EFFECTOR CELL; IMMUNOCOMPETENT CELL; IMMUNOGENICITY; NEOADJUVANT THERAPY; PRECANCER; PREDICTION; PREDICTIVE VALUE; REVIEW; SUPPRESSOR CELL; TUMOR ASSOCIATED LEUKOCYTE; TUMOR ESCAPE; BREAST TUMOR; FEMALE; GENETICS; IMMUNOLOGY; IMMUNOTHERAPY; ONCOLOGY; PATHOLOGY; PROCEDURES; PROGNOSIS;

BIOMARKERS, TUMOR; BREAST NEOPLASMS; FEMALE; GENOMICS; HUMANS; IMMUNOTHERAPY; MEDICAL ONCOLOGY; PROGNOSIS;

EID: 85033241953     PISSN: 1044579X     EISSN: 10963650     Source Type: Journal    
DOI: 10.1016/j.semcancer.2017.11.003     Document Type: Review

References (159)

1. Farkona, S., Diamandis, E.P., Blasutig, I.M., Cancer immunotherapy: the beginning of the end of cancer?. BMC Med., 14(1), 2016, 73.
2. Angelova, M., et al. Characterization of the immunophenotypes and antigenomes of colorectal cancers reveals distinct tumor escape and novel targets for immunotherapy. Genome Biol., 16(1), 2015, 64.
3. Charoentong, P., Finotello, F., Angelova, M., Mayer, C., Pan-cancer immunogenomic analyses reveal genotype-immunophenotype relationships and predictors of response to checkpoint blockade. bioRxiv, 2016, 56101.
4. Chang, L.-S., et al. Toll-like receptor 9 agonist enhances anti-tumor immunity and inhibits tumor-associated immunosuppressive cells numbers in a mouse cervical cancer model following recombinant lipoprotein therapy. Mol. Cancer, 13(January (1)), 2014, 60.
5. Liu, X.S., Mardis, E.R., Applications of immunogenomics to cancer. Cell 168:4 (2017), 600–612.
6. Degnim, A.C., et al. Immune cell quantitation in normal breast tissue lobules with and without lobulitis. Breast Cancer Res. Treat. 144:3 (2014), 539–549.
7. Atabai, K., Sheppard, D., Werb, Z., Roles of innate immune system in mammary gland remodeling during involution. J. Mammary Gland Biol. Neoplasia 12 (2007), 37–45.
8. Hussein, M.R., Hassan, H.I., Analysis of the mononuclear inflammatory cell infiltrate in the normal breast, benign proliferative breast disease, in situ and infiltrating ductal breast carcinomas: preliminary observations. J. Clin. Pathol. 59:9 (2006), 972–977.
9. Alfonso, J.C.L., Schaadt, N.S., Schönmeyer, R., Brieu, N., Forestier, G., Wemmert, C., In-silico insights on the prognostic potential of immune cell infiltration patterns in the breast lobular epithelium. Nat. Publ. Gr.(April), 2016, 1–18.
10. Beckmann, M.W., Niederacher, D., Schnüren, H.G., Gusterson, B.A., Bender, H.G., Multistep carcinogenesis of breast cancer and tumour heterogeneity. J. Mol. Med. 75:6 (1997), 429–439.
11. Kristensen, V.N., et al. Integrated molecular profiles of invasive breast tumors and ductal carcinoma in situ (DCIS) reveal differential vascular and interleukin signaling. Proc. Natl. Acad. Sci. U. S. A. 109:8 (2012), 2802–2807.
12. Pruneri, G., et al. The prevalence and clinical relevance of tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ of the breast. Ann. Oncol.(September), 2016 p. mdw623.
13. Gil Del Alcazar, C.R., et al. Immune escape in Breast cancer during In situ to invasive carcinoma transition. Cancer Discov., 2017 p. CD-17-0222.
14. Thompson, E., et al. The immune microenvironment of breast ductal carcinoma in situ. Mod. Pathol. 29:3 (2016), 249–258.
15. Mohammed, Z.M., Going, J.J., Edwards, J., Elsberger, B., McMillan, D.C., The relationship between lymphocyte subsets and clinico-pathological determinants of survival in patients with primary operable invasive ductal breast cancer. Br. J. Cancer 109:6 (2013), 1676–1684.
16. Wasserman, J.K., Parra-Herran, C., Regressive change in high-grade ductal carcinoma in situ of the breast: histopathologic spectrum and biologic importance. Am. J. Clin. Pathol. 144:3 (2015), 503–510.
17. Denkert, C., et al. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J. Clin. Oncol. 28:1 (2010), 105–113.
18. García-Martínez, E., et al. Tumor-infiltrating immune cell profiles and their change after neoadjuvant chemotherapy predict response and prognosis of breast cancer. Breast Cancer Res. 16 (2014), 1–17.
19. Dushyanthen, S., et al. Relevance of tumor-infiltrating lymphocytes in breast cancer. BMC Med., 13(202), 2015.
20. Miyan, M., et al. Differential tumor infiltration by T-cells characterizes intrinsic molecular subtypes in breast cancer. J. Transl. Med., 227, 2016.
21. Varn, F.S., Andrews, E.H., Mullins, D.W., Cheng, C., Integrative analysis of breast cancer reveals prognostic haematopoietic activity and patient-specific immune response profiles. Nat. Commun., 7, 2016, 10248.
22. Nagalla, S., et al. Interactions between immunity, proliferation and molecular subtype in breast cancer prognosis. Genome Biol., 14(4), 2013, R34.
23. Alistar, A., Chou, J.W., Nagalla, S., Black, M.A., D'Agostino, R., Miller, L.D., Dual roles for immune metagenes in breast cancer prognosis and therapy prediction. Genome Med., 6(10), 2014, 80.
24. Salgado, R., et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann. Oncol. 26:2 (2015), 259–271.
25. Denkert, C., et al. Standardized evaluation of tumor-infiltrating lymphocytes in breast cancer: results of the ring studies of the international immuno-oncology biomarker working group. Mod. Pathol. 29:10 (2016), 1155–1164.
26. Mao, Y., Qu, Q., Chen, X., Huang, O., Wu, J., Shen, K., The prognostic value of tumor-infiltrating lymphocytes in breast cancer: a systematic review and meta-analysis. PLoS One 11:4 (2016), 1–13.
27. Liu, S., Lachapelle, J., Leung, S., Gao, D., Foulkes, W.D., Nielsen, T.O., CD8+ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer. Breast Cancer Res., 14(2), 2012, R48.
28. Mohammed, Z.M.A., Going, J.J., Edwards, J., McMillan, D.C., The role of the tumour inflammatory cell infiltrate in predicting recurrence and survival in patients with primary operable breast cancer. Cancer Treat. Rev. 38:8 (2012), 943–955.
29. Chen, Z., et al. Intratumoral CD8+ cytotoxic lymphocyte is a favorable prognostic marker in node-negative breast cancer. PLoS One, 4, 2014.
30. Liu, S., et al. Prognostic significance of FOXP3+ tumor-infiltrating lymphocytes in breast cancer depends on estrogen receptor and human epidermal growth factor receptor-2 expression status and concurrent cytotoxic T-cell infiltration. Breast Cancer Res., 16(5), 2014, 432.
31. Mulligan, A.M., et al. Tumoral lymphocytic infiltrate and expression of the chemokine CXCL10 in Breast cancers from the Ontario familial breast cancer registry. Clin. Cancer Res. 19:January (2) (2013), 336–346.
32. West, N.R., et al. Tumour-infiltrating FOXP3(+) lymphocytes are associated with cytotoxic immune responses and good clinical outcome in oestrogen receptor-negative breast cancer. Br. J. Cancer 108:1 (2013), 155–162.
33. Linsley, P.S., Chaussabel, D., Speake, C., The relationship of immune cell signatures to patient survival varies within and between tumor types. PLoS One 10:9 (2015), 1–19.
34. Jia, W., et al. The peripheral blood neutrophil-to-lymphocyte ratio is superior to the lymphocyte-to-monocyte ratio for predicting the long-term survival of triple-negative breast cancer patients. PLoS One 10:11 (2015), 1–13.
35. Ali, H.R., Chlon, L., Pharoah, P.D.P., Markowetz, F., Caldas, C., Patterns of immune infiltration in Breast cancer and their clinical implications: a gene-expression-based retrospective study. PLoS Med. 13:12 (2016), 1–24.
36. Bergenfelz, C., et al. Systemic monocytic-MDSCs are generated from monocytes and correlate with disease progression in breast cancer patients. PLoS One, 10(5), 2015.
37. Diaz-montero, C.M., Salem, M.L., Nishimura, M.I., Garett-Mayer, E., Cole, D.J., Montero, A.J., Increased circulating myeloid-derived suppressor cells correlate with clinical cancer stage, metastasic burden, and doxorubicin-cyclophosphamide chemotherapy. Cancer Immunol. Immunother. 58:1 (2009), 49–59.
38. Solito, S., et al. A human promyelocytic-like population is responsible for the immune suppression mediated by myeloid-derived suppressor cells. Blood 118:8 (2011), 1–4 201AD.
39. Xing, C., The neutrophil lymphocyte ratio is associated with breast cancer prognosis: an updated systematic review and meta-analysis. Onco. Targets Ther., 2016, 5567–5575.
40. Verma, C., et al. Natural killer (NK) cell profiles in blood and tumour in women with large and locally advanced breast cancer (LLABC) and their contribution to a pathological complete response (PCR) in the tumour following neoadjuvant chemotherapy (NAC): differential rest. J. Transl. Med., 180, 2015.
41. Gentles, A.J., et al. The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat. Med. 21:8 (2015), 938–945.
42. Jiang, X., Shapiro, D.J., The immune system and inflammation in breast cancer. Mol. Cell. Endocrinol. 382:1 (2014), 673–682.
43. Iglesia, M.D., et al. Prognostic B-cell signatures using mRNA-seq in patients with subtype-specific breast and ovarian cancer. Clin. Cancer Res. 20:14 (2014), 3818–3829.
44. Ali, H.R., et al. Innate and adaptive immune cells in the tumor microenvironment. Nat. Immunol. 13:10 (2015), 1014–1022.
45. Ye, J., et al. Specific recruitment of γδ regulatory T cells in human breast cancer. Cancer Res. 73:20 (2013), 6137–6148.
46. Ma, C., et al. Tumor-infiltrating γδ T lymphocytes predict clinical outcome in human breast cancer. J. Immunol. 189:10 (2012), 5029–5036.
47. Peiris-Pagès, M., Sotgia, F., Lisanti, M.P., Chemotherapy induces the cancer-associated fibroblast phenotype, activating paracrine Hedgehog-GLI signalling in breast cancer cells. Oncotarget 6:13 (2015), 10728–10745.
48. Ignatiadis, M., Singhal, C., Haibe-kains, B., Criscitiello, C., Gene modules and response to neoadjuvant chemotherapy in Breast cancer subtypes: a pooled analysis. J. Clin. Oncol., 30(16), 2012.
49. Sota, Y., et al. Construction of novel immune-related signature for prediction of pathological complete response to neoadjuvant chemotherapy in human breast cancer. Ann. Oncol. 25:1 (2014), 100–106.
50. C. Denkert et al., Evaluation of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarker in different subtypes of breast cancer treated with neoadjuvant therapy − A metaanalysis of 3771 patients, San Antonia Breast Cancer Symp., vol. Abstract S, (2016).
51. Gu-Trantien, C., et al. CD4+ follicular helper T cell infiltration predicts breast cancer survival. J. Clin. Invest. 123:7 (2013), 1–20.
52. Wang, K., Xu, J., Zhang, T., Xue, D., Tumor-infiltrating lymphocytes in breast cancer predict the response to chemotherapy and survival outcome: a meta-analysis. Oncotarget, 7(28), 2016.
53. Verma, R., et al. Lymphocyte depletion and repopulation after chemotherapy for primary breast cancer. Breast Cancer Res., 18(1), 2016, 10.
54. West, N.R., Milne, K., Truong, P.T., Macpherson, N., Nelson, B.H., Watson, P.H., Tumor-infiltrating lymphocytes predict response to anthracycline-based chemotherapy in estrogen receptor-negative breast cancer. Breast Cancer Res., 13(6), 2011, R126.
55. Standish, L.J., et al. Immune defects in breast cancer patients after radiotherapy. J. Soc. Integr Oncol. 6:3 (2008), 110–121.
56. Bernal-Estévez, D., Sánchez, R., Tejada, R.E., Parra-López, C., Chemotherapy and radiation therapy elicits tumor specific T cell responses in a breast cancer patient. BMC Cancer, 16(1), 2016, 591.
57. Zheng, L.H., Zhao, Y.H., Feng, H.L., Liu, Y.J., Endocrine resistance in breast cancer. Climacteric 17:5 (2014), 522–528.
58. Selli, C., Dixon, J.M., Sims, A.H., Accurate prediction of response to endocrine therapy in breast cancer patients: current and future biomarkers. Breast Cancer Res., 18(1), 2016, 118.
59. Engels, C.C., et al. The prognostic and predictive value of Tregs and tumor immune subtypes in postmenopausal, hormone receptor-positive breast cancer patients treated with adjuvant endocrine therapy: a Dutch TEAM study analysis. Breast Cancer Res. Treat. 149:3 (2015), 587–596.
60. Behjati, S., Frank, M.H., The effects of tamoxifen on immunity. Curr. Med. Chem. 16:24 (2009), 3076–3080.
61. Arnould, L., et al. Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism?. Br. J. Cancer 94:2 (2006), 259–267.
62. Andre, F., et al. Molecular pathways: involvement of immune pathways in the therapeutic response and outcome in breast cancer. Clin. Cancer Res. 19:1 (2013), 28–33.
63. Varadan, V., et al. Immune signatures following single dose trastuzumab predict pathologic response to preoperativetrastuzumab and chemotherapy in HER2-positive early breast cancer. Clin. Cancer Res. 22:13 (2016), 3249–3259.
64. Loi, S., et al. Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial. Ann. Oncol. 25:8 (2014), 1544–1550.
65. S.-R. Kim, et al. A surrogate gene expression signature of tumor infiltrating lymphocytes (TILs) predicts degree of benefit from trastuzumab added to standard adjuvant chemotherapy in NSABP (NRG) trial B-31 for HER2+ breast cancer, Proc. 106th Annu. Meet. Am. Assoc. Cancer Res., vol. Philadelph, no. 75(15 Suppl):Abstractnr 2837.
66. Perez, E.A., et al. Association of stromal tumor-Infiltrating lymphocytes with recurrence-Free survival in the N9831 adjuvant trial in patients with early-stage HER2-positive breast cancer. JAMA Oncol. 2:1 (2016), 56–64.
67. Perez, E.A., et al. Genomic analysis reveals that immune function genes are strongly linked to clinical outcome in the north central cancer treatment group N9831 adjuvant trastuzumab trial. J. Clin. Oncol. 33:7 (2015), 701–708.
68. Adams, S., ENlisting the immune system to cure breast cancer—a recipe for success. JAMA Oncol. 2:1 (2016), 25–27.
69. Gingras, I., Azim, H.A., Ignatiadis, M., Sotiriou, C., Immunology and breast cancer: toward a new way of understanding breast cancer and developing novel therapeutic strategies. Clin. Adv. Hematol. Oncol. 13:6 (2015), 372–382.
70. Kang, J., Demaria, S., Formenti, S., Current clinical trials testing the combination of immunotherapy with radiotherapy. J. Immunother. Cancer, 4(1), 2016, 51.
71. Tamkus, D., Joginpally, T., Therapeutic strategies to reverse immunosuppressive breast cancer microenvironment. Oncol. Discov., 4(1), 2016, 1.
72. Czerniecki, B.J., et al. Targeting HER-2/neu in early breast cancer development using dendritic cells with staged interleukin-12 burst secretion. Cancer Res. 67:4 (2007), 1842–1852.
73. Koski, G.K., et al. A novel dendritic cell-Based immunization approach for the induction of durable th1-polarized anti-HER2/neu responses in women with early Breast cancer. J. Immunother. 35:1 (2013), 54–65.
74. Sharma, A., et al. Her-2 pulsed dendritic cell vaccine can eliminate HER-2 expression and impact DCIS. Cancer 118:17 (2012), 4354–4362.
75. Bernhard, H., et al. Adoptive transfer of autologous, HER2-specific, cytotoxic T lymphocytes for the treatment of HER2-overexpressing breast cancer. Cancer Immunol. Immunother. 57:2 (2008), 271–280.
76. Lum, L.G., et al. Targeted t cell therapy in stage IV Breast cancer: a phase I clinical trial. Clin. Cancer Res., 2015, 2305–2314.
77. Hardy, N.M., et al. Phase I trial of adoptive cell transfer with mixed-profile type-I/type-II allogeneic T cells for metastatic breast cancer. Clin. Cancer Res. 17:21 (2011), 6878–6887.
78. a Geller, M., et al. A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and Breast cancer. Cytotherapy 13:1 (2013), 98–107.
79. Vonderheide, R.H., et al. Tremelimumab in combination with exemestane in patients with advanced breast cancer and treatment-associated modulation of inducible costimulator expression on patient T cells. Clin. Cancer Res. 16:13 (2010), 3485–3494.
80. Nanda, R., et al. Pembrolizumab in patients with advanced triple-negative breast cancer: phase Ib keynote-012 study. J. Clin. Oncol. 34:21 (2016), 2460–2467.
81. Adams, S., et al. Phase 2 study of pembrolizumab as first-line therapy for PD-L1-positive metastatic triple-negative breast cancer (mTNBC):Preliminary data from KEYNOTE-086 cohort B. J. Clin. Oncol., 35(Suppl), 2017 abstr 1088.
82. Augusto Santa-Maria, C., et al. Durvalumab and tremelimumab in metastatic breast cancer (MBC): immunotherapy and immunopharmacogenomic dynamics. J. Clin. Oncol., 35(Suppl), 2017 abstr 3052.
83. Brahmer, J.R., et al. Safety and activity of anti-PD-L1 antibody in patients with advanced caancer. N. Engl. J. Med. 366:26 (2012), 2455–2465.
84. L. Dirix et al. Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: A phase Ib JAVELIN solid tumor trial, 38th Annu. San Antonio Breast Cancer Symp., vol. abstract: p. 10718, 2015.
85. I. Dua and A. R. Tan, Immunotherapy for Triple-Negative Breast Cancer: A Focus on Immune Checkpoint Inhibitors, pp. 20–27.
86. S. et al. Loi, LBA13 − Relationship between tumor infiltrating lymphocyte (TIL) levels and response to pembrolizumab (pembro) in metastatic triple-negative breast cancer (mTNBC): results from KEYNOTE-086, ESMO Annu. Meet., vol. September, no. Abstract LBA13, 2017.
87. Nanda, R., et al. Pembrolizumab plus standard neoadjuvant therapy for high-risk breast cancer (BC): Results from I-SPY 2. J. Clin. Oncol., 35(Suppl), 2017 abstr: 506.
88. Adams, S., et al. Phase Ib trial of atezolizumab in combination with nab-paclitaxel in patients with metastatic triple-negative breast cancer (mTNBC). J. Clin. Oncol.(Suppl), 2016 ASCO Annua, abstr: 1009.
89. Brignone, C., et al. First-line chemoimmunotherapy in metastatic breast carcinoma: combination of paclitaxel and IMP321 (LAG-3Ig) enhances immune responses and antitumor activity. J. Transl. Med., 71, 2010.
90. Melero, I., et al. Therapeutic vaccines for cancer: an overview of clinical trials. Nat. Rev. Clin. Oncol., 2014.
91. Criscitiello, C., Tumor-associated antigens in breast cancer. Breast Care 7:4 (2012), 262–266.
92. Glenn, W.K., Heng, B., Delprado, W., Iacopetta, B., Whitaker, N.J., Lawson, J.S., Epstein-Barr virus, human papillomavirus and mouse mammary tumour virus as multiple viruses in breast cancer. PLoS One, 7(11), 2012.
93. Wang-Johanning, F., et al. Human endogenous retrovirus type K antibodies and mRNA as serum biomarkers of early-stage breast cancer. Int. J. Cancer 134:3 (2013), 587–595.
94. Ariad, S., Milk, N., Bolotin, A., Gopas, J., Sion-Vardy, N., Benharoch, D., Measles virus antigens in breast cancer. Anticancer Res. 31:3 (2011), 913–920.
95. Taher, C., et al. High prevalence of human cytomegalovirus proteins and nucleic acids in primary breast cancer and metastatic sentinel lymph nodes. PLoS One, 6795, 2013.
96. Michaelis, M., Doerr, H.W., Cinatl, J., The story of human cytomegalovirus and cancer: increasing evidence and open questions. Neoplasia 11:1 (2009), 1–9.
97. Taylor, M., Bolton, L.M., Johnson, P., Elliott, T., Murray, N., Breast cancer is a promising target for vaccination using cancer-testis antigens known to elicit immune responses. Breast Cancer Res., 9(4), 2007, R46.
98. Saini, S., Jagadish, N., Gupta, A., Bhatnagar, A., Suri, A., A novel cancer testis antigen, A-Kinase anchor protein 4 (AKAP4) is a potential biomarker for Breast cancer. PLoS One, 8(2), 2013.
99. Chen, Y.T., et al. Multiple cancer/testis antigens are preferentially expressed in hormone-receptor negative and high-grade breast cancers. PLoS One 6:3 (2011), 1–9.
100. Adams, S., et al. Expression of cancer testis antigens in human BRCA-associated breast cancers: potential targets for immunoprevention?. Cancer Immunol. Immunother. 60:7 (2011), 999–1007.
101. Balafoutas, D., et al. Cancer testis antigens and NY-BR-1 expression in primary breast cancer: prognostic and therapeutic implications. BMC Cancer, 13(1), 2013, 271.
102. Yang, F., et al. MAGEC2, an epithelial-mesenchymal transition inducer, is associated with breast cancer metastasis. Breast Cancer Res. Treat. 145:1 (2014), 23–32.
103. Gjerstorff, M.F., Andersen, M.H., Ditzel, H.J., Gjerstorff, M.F., Andersen, M.H., Ditzel, H.J., Oncogenic cancer/testis antigens: prime candidates for immunotherapy. Oncotarget 6:18 (2015), 15772–15787.
104. Alexandrov, L.B., et al. Signatures of mutational processes in human cancer. Nature 500 (2013), 415–421.
105. Schumacher, T.N., Schreiber, R.D., Neoantigens in cancer immunotherapy. Science 348:6230 (2015), 69–74.
106. Budczies, J., et al. Classical pathology and mutational load of breast cancer − integration of two worlds. J. Pathol. Clin. Res. 1:4 (2015), 225–238.
107. Cescon, D.W., Haibe-Kains, B., Mak, T.W., APOBEC3B expression in breast cancer reflects cellular proliferation, while a deletion polymorphism is associated with immune activation. Proc. Natl. Acad. Sci. U. S. A. 112:9 (2015), 2841–2846.
108. Sieuwerts, A.M., et al. Elevated APOBEC3B correlates with poor outcomes for estrogen-Receptor-Positive Breast cancers. Horm. Cancer 40 (2014), 5–413.
109. Smid, M., et al. Breast cancer genome and transcriptome integration implicates specific mutational signatures with immune cell infiltration. Nat. Commun., 7, 2016, 12910.
110. Kotoula, V., et al. Tumor infiltrating lymphocytes affect the outcome of patients with operable triple-negative breast cancer in combination with mutated amino acid classes. PLoS One 11:9 (2016), 1–17.
111. Dunn, G.P., Bruce, A.T., Ikeda, H., Old, L.J., Schreiber, R.D., Cancer immunoediting: from immuno- surveillance to tumor escape. Nat. Immunol. 3:11 (2002), 991–998.
112. Rooney, M.S., Shukla, S.A., Wu, C.J., Getz, G., Hacohen, N., Molecular and genetic properties of tumors associated with local immune cytolytic activity. Cell 160:1–2 (2015), 48–61.
113. Straetemans, T., et al. Recurrence of melanoma following t cell treatment: continued antigen expression in a tumor that evades t cell recruitment. Mol. Ther. 23:2 (2015), 396–406.
114. Forero, A., et al. Expression of the MHC class II pathway in triple-negative breast cancer tumor cells is associated with a good prognosis and infiltrating lymphocytes. Cancer Immunol. Res., 2016, 1–11.
115. Kaneko, K., et al. Clinical implication of HLA class I expression in breast cancer. BMC Cancer, 11(1), 2011, 454.
116. da Silva, G.B.R.F., et al. Expression of the classical and nonclassical HLA molecules in Breast cancer. Int. J. Breast Cancer, 2013, 2013, 250435.
117. Harada, A., et al. Clinical implication of human leukocyte antigen (HLA) −F expression in breast cancer. Pathol. Int. 65 (2015), 569–574.
118. Vitale, M., Rezzani, R., Rodella, L., Down-regulation, T.A.P., Breast, H.P., Zauli, G., HLA class i antigen and transporter associated with antigen processing (TAP1 and TAP2) down-Regulation in high-grade primary breast carcinoma lesions HLA class I antigen and transporter associated with antigen processing. Cancer Res. 58:914 (1998), 737–742.
119. Palmisano, G.L., et al. Investigation of HLA class I downregulation in breast cancer by RT-PCR. Hum. Immunol. 62:2 (2001), 133–139.
120. Shin, D.S., et al. Primary resistance to PD-1 blockade mediated by JAK1/2 mutations. Cancer Discov., 2016.
121. Zaretsky, J.M., et al. Mutations associated with acquired resistance to PD-1 blockade in melanoma. N. Engl. J. Med. 375:9 (2016), 819–829.
122. Yates, L.R., et al. Genomic evolution of breast cancer metastasis and relapse. Cancer Cell 32:2 (2017), 169–184 (e7).
123. Peng, W., et al. Loss of PTEN promotes resistance to T cell? Mediated immunotherapy. Cancer Discov. 6:2 (2016), 202–216.
124. Luen, S., Virassamy, B., Savas, P., Salgado, R., Loi, S., The genomic landscape of breast cancer and its interaction with host immunity. Breast 29 (2016), 241–250.
125. Loi, S., et al. RAS/MAPK activation is associated with reduced tumor-infiltrating lymphocytes in triple-negative breast cancer: therapeutic cooperation between MEK and PD-1/PD-L1 immune checkpoint inhibitors. Clin. Cancer Res. 22:6 (2016), 1499–1509.
126. Debets, R., Donnadieu, E., Chouaib, S., Coukos, G., TCR-engineered T cells to treat tumors: seeing but not touching?. Semin. Immunol. 28:1 (2016), 10–21.
127. Yan Mao, J.W., Keller, T. Evan, Garfield, H. David, Shen, Kunwei, Stroma cells in tumor microenvironment and Breast cancer. Cancer Metastasis Rev. 32:0 (2013), 303–315.
128. Esquivel-Velázquez, M., Ostoa-Saloma, P., Palacios-Arreola, M.I., Nava-Castro, K.E., Castro, J.I., Morales-Montor, J., The role of cytokines in Breast cancer development and progression. J. Interf. Cytokine Res. 35:1 (2015), 1–16.
129. Ward, R., et al. Monocytes and macrophages, implications for breast cancer migration and stem cell-like activity and treatment. Oncotarget 6:16 (2015), 14687–14699.
130. Lindau, D., Gielen, P., Kroesen, M., Wesseling, P., Adema, G.J., The immunosuppressive tumour network: myeloid-derived suppressor cells, regulatory T cells and natural killer T cells. Immunology 138:Feburary (2) (2013), 105–115.
131. Law, A.M.K., Lim, E., Ormandy, C.J., Gallego-Ortega, D., The innate and adaptive infiltrating immune systems as targets for breast cancer immunotherapy. Endocr. Relat. Cancer 24:4 (2017), R123–R144.
132. Smith, E.L., Zamarin, D., Lesokhin, A.M., Harnessing the immune system for cancer therapy. Curr. Opin. Oncol. 26:6 (2014), 600–607.
133. Trella, E., et al. Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer. Breast Cancer Res. Treat., 1, 2014.
134. Bertucci, F., et al. PDL1 expression in inflammatory breast cancer is frequent and predicts for the pathological response to chemotherapy. Oncotarget, 6, 2016, 15.
135. Mittendorf, E.A., et al. PD-L1 expression in triple negative Breast cancer. Cancer Immunol. Res. 2:4 (2014), 361–370.
136. Sabatier, R., et al. Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget, 6(7), 2014.
137. Kolacinska, A., et al. Immune checkpoints: cytotoxic T-lymphocyte antigen 4 and programmed cell death protein 1 in breast cancer surgery. Oncol. Lett., 2015, 1079–1086.
138. Buisseret, L., Garaud, S., De Wind, A., Van Den Eynden, G., Boisson, A., Solinas, C., Tumor-in fi ltrating lymphocyte composition, organization and PD-1/PD-L1 expression are linked in breast cancer. Oncoimmunology, 6(1), 2017.
139. Bottai, G., et al. An immune stratification reveals a subset of PD-1/LAG-3 double-positive triple-negative breast cancers. Breast Cancer Res., 18(1), 2016, 121.
140. Zhu, S., Lin, J., Qiao, G., Wang, X., Xu, Y., Tim-3 identifies exhausted follicular helper T cells in breast cancer patients. Immunobiology, 2016, 1–8.
141. Arnedos, M., et al. 351Ogenomic and immune characterization of metastatic breast cancer (mbc): and ancillary study of the safir01 & moscato trials. Ann. Oncol., 25(Suppl. 4), 2014 p. iv116-iv116.
142. Voutsadakis, I.A., et al. Immune blockade inhibition in breast cancer. Anticancer Res. 36:11 (2016), 5607–5622.
143. Demaria, S., et al. Development of tumor-infiltrating lymphocytes in Breast cancer after neoadjuvant paclitaxel chemotherapy development of tumor-infiltrating lymphocytes in breast cancer after neoadjuvant paclitaxel chemotherapy 1. Clin. Cancer Res. 7:October (2001), 3025–3030.
144. Karpf, A.R., Potential role for epigenetic modulatory drugs in the enhancement of cancer/germ-line antigen vaccine efficacy. Epigenetics 1:3 (2006), 116–120.
145. Dunn, J., Rao, S., Epigenetics and immunotherapy: the current state of play. Mol. Immunol. 87:April (2017), 227–239.
146. Mazzone, R., Zwergel, C., Mai, A., Valente, S., Epi-drugs in combination with immunotherapy: a new avenue to improve anticancer efficacy. Clin. Epigenetics, 9(1), 2017, 59.
147. Liontos, M., Anastasiou, I., Bamias, A., Dimopoulos, M.-A., DNA damage, tumor mutational load and their impact on immune responses against cancer. Ann Transl. Med., 4(14), 2016, 264.
148. M. et al. Kok, Adaptive phase II randomized non-comparative trial of nivolumab after induction treatment in triple negative breast cancer: TONIC-trial., Present. Eur. Soc. Med. Oncol. 2017 Congr. Madrid, Spain, vol. September, no. Abstract LBA14, 2017.
149. Butt, A.Q., Mills, K.H.G., Immunosuppressive networks and checkpoints controlling antitumor immunity and their blockade in the development of cancer immunotherapeutics and vaccines. Oncogene 33:38 (2013), 4623–4631.
150. Camisaschi, C., et al. Targeting immune regulatory networks to counteract immune suppression in cancer. Vaccines, 2016, 1–17.
151. Park, J.W., Melisko, M.E., Esserman, L.J., Jones, L.A., Wollan, J.B., Sims, R., Treatment with autologous antigen-presenting cells activated with the HER-2 −based antigen lapuleucel-T: Results of a phase I study in immunologic and clinical activity in HER-2-overexpressing breast cancer. J. Clin. Oncol. 25:24 (2007), 3680–3687.
152. Qi, C.J., et al. Autologous dendritic cell vaccine for estrogen receptor (ER)/progestin receptor (PR) double-negative breast cancer. Cancer Immunol. Immunother. 61:9 (2012), 1415–1424.
153. Svane, I.M., Pedersen, A.E., Nikolajsen, K., Zocca, M.B., Alterations in p53-specific T cells and other lymphocyte subsets in breast cancer patients during vaccination with p53-peptide loaded dendritic cells and low-dose interleukin-2. Vaccine 26:36 (2008), 4716–4724.
154. Tiriveedhi, V., et al. Mammaglobin-A cDNA vaccination of Breast cancer patients induces antigen-Specific cytotoxic CD4 + ICOShi T cells. Breast Cancer Res. Treat. 138:1 (2013), 109–118.
155. Mittendorf, E.A., et al. Clinical trial results of the HER-2/neu (E75) vaccine to prevent Breast cancer recurrence in high-Risk patients. Cancer 118:10 (2013), 2594–2602.
156. Dols, A., et al. Vaccination of women with metastatic breast cancer, using a costimulatory gene ({CD80)-modified}, {HLA-A2-matched}, allogeneic, breast cancer cell line: clinical and immunological results. Hum. Gene Ther. 14:11 (2003), 1117–1123.
157. Gates, J.D., et al. Circulating regulatory T cells (CD4 + CD25 + FOXP3+) decrease in breast cancer patients after vaccination with a modified MHC class II HER2/neu (AE37) peptide. Vaccine 28:47 (2010), 7476–7482.
158. Vassilaros, S., Tsibanis, A., Tsikkinis, A., a Pietersz, G., McKenzie, I.F.C., Apostolopoulos, V., Up to 15-year clinical follow-up of a pilot Phase III immunotherapy study in stage II breast cancer patients using oxidized mannan-MUC1. Immunotherapy 5:11 (2013), 1177–1182.
159. Meraviglia, S., et al. In vivo manipulation of V9V2 T cells with zoledronate and low-dose interleukin-2 for immunotherapy of advanced breast cancer patients. Clin. Exp. Immunol. 161:2 (2010), 290–297.