Cellular Immune Responses and Immune Escape Mechanisms in Breast Cancer: Determinants of Immunotherapy

Breast Care

Volumn 11, Issue 2, 2016, Pages 102-107

  Domschke, Christoph ^a   Schneeweiss, Andreas ^a   Stefanovic, Stefan ^a   Wallwiener, Markus ^a   Heil, Joerg ^a   Rom, Joachim ^a   Sohn, Christof ^b   Schuetz, Florian ^a  

^a UNIVERSITY HOSPITAL HEIDELBERG   (Germany)

^b UNIVERSITY HOSPITAL REGENSBURG   (Germany)

Author keywords

Breast cancer; Cellular immunity; Immune escape; Immunoediting; Immunosurveillance; Immunotherapy

Indexed keywords

ANTHRACYCLINE; CANCER VACCINE; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; IMMUNOMODULATING AGENT; PROGRAMMED DEATH 1 LIGAND 1; PROGRAMMED DEATH 1 RECEPTOR; TUMOR ANTIGEN; VACCINE;

ADOPTIVE IMMUNOTHERAPY; ADOPTIVE TRANSFER; ANTIGEN PRESENTING CELL; BONE MARROW; BREAST CANCER; CANCER ADJUVANT THERAPY; CANCER IMMUNIZATION; CANCER IMMUNOTHERAPY; CANCER LOCALIZATION; CANCER PROGNOSIS; CANCER RECURRENCE; CELLULAR IMMUNITY; DISTANT METASTASIS; HUMAN; IMMUNE EVASION; IMMUNOSURVEILLANCE; IMMUNOTHERAPY; NONHUMAN; OVERALL SURVIVAL; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; REVIEW; TUMOR ESCAPE; TUMOR IMMUNITY;

EID: 84966460133     PISSN: 16613791     EISSN: 16613805     Source Type: Journal    
DOI: 10.1159/000446061     Document Type: Review

References (83)

1. Mittal D, Gubin MM, Schreiber RD, Smyth MJ: New insights into cancer immunoediting and its three component phases-elimination, equilibrium and escape. Curr Opin Immunol 2014; 27: 16-25
2. Schreiber RD, Old LJ, Smyth MJ: Cancer immunoediting: integrating immunity's roles in cancer suppression and promotion. Science 2011; 331: 1565-1570
3. Dushyanthen S, Beavis PA, Savas P, et al.: Relevance of tumor-infiltrating lymphocytes in breast cancer. BMC Med 2015; 13: 202
4. Datta J, Berk E, Cintolo JA, et al.: Rationale for a multimodality strategy to enhance the efficacy of dendritic cell-based cancer immunotherapy. Front Immunol 2015; 6: 271
5. Ravelli A, Reuben JM, Lanza F, et al.: Immune-related strategies driving immunotherapy in breast cancer treatment: a real clinical opportunity. Expert Rev Anticancer Ther 2015; 15: 689-702
6. Demicheli R: Tumour dormancy: findings and hypotheses from clinical research on breast cancer. Sem Cancer Biol 2001; 11: 297-306
7. Diel IJ, Kaufmann M, Costa SD, et al.: Micrometastatic breast cancer cells in bone marrow at primary surgery: prognostic value in comparison with nodal status. J Natl Cancer Inst 1996; 88: 1652-1658
8. Braun S, Vogl FD, Naume B, et al.: A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 2005; 353: 793-802
9. Domschke C, Diel IJ, Englert S, et al.: Prognostic value of disseminated tumor cells in the bone marrow of patients with operable primary breast cancer: a long-term follow-up study. Ann Surg Oncol 2013; 20: 1865-1871
10. Hartkopf AD, Taran FA, Wallwiener M, et al.: Prognostic relevance of disseminated tumour cells from the bone marrow of early stage breast cancer patients-results from a large single-centre analysis. Eur J Cancer 2014; 50: 2550-2559
11. Banys M, Krawczyk N, Fehm T: The role and clinical relevance of disseminated tumor cells in breast cancer. Cancers (Basel) 2014; 6: 143-152
12. Pages F, Galon J, Dieu-Nosjean MC, et al.: Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene 2010; 29: 1093-1102
13. Calabro A, Beissbarth T, Kuner R, et al.: Effects of infiltrating lymphocytes and estrogen receptor on gene expression and prognosis in breast cancer. Breast Cancer Res Treat 2009; 116: 69-77
14. Rody A, Holtrich U, Pusztai L, et al.: T-cell metagene predicts a favorable prognosis in estrogen receptornegative and HER2-positive breast cancers. Breast Cancer Res 2009; 11:R15
15. Ono M, Tsuda H, Shimizu C, et al.: Tumor-infiltrating lymphocytes are correlated with response to neoadjuvant chemotherapy in triple-negative breast cancer. Breast Cancer Res Treat 2012; 132: 793-805
16. Lee HJ, Seo JY, Ahn JH, et al.: Tumor-associated lymphocytes predict response to neoadjuvant chemotherapy in breast cancer patients. J Breast Cancer 2013; 16: 32-39
17. Denkert C, Loibl S, Noske A, et al.: Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol 2010; 28: 105-113
18. West NR, Milne K,Truong PT, et al.: Tumor-infiltrating lymphocytes predict response to anthracyclinebased chemotherapy in estrogen receptor-negative breast cancer. Breast Cancer Res 2011; 13:R126
19. Loi S, Sirtaine N, Piette F, et al.: Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in nodepositive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98. J Clin Oncol 2013; 31: 860-867
20. Andre F, Dieci MV, Dubsky P, et al.: Molecular pathways: involvement of immune pathways in the therapeutic response and outcome in breast cancer. Clin Cancer Res 2013; 19: 28-33
21. Loi S: Tumor-infiltrating lymphocytes, breast cancer subtypes and therapeutic efficacy. Oncoimmunology 2013; 2:e24720
22. Feuerer M, Beckhove P, Garbi N, et al.: Bone marrow as a priming site for T-cell responses to blood-borne antigen. Nature Med 2003; 9: 1151-1157
23. Stefanovic S, Schuetz F, Sohn C, et al.: Bone marrow microenvironment in cancer patients: immunological aspects and clinical implications. Cancer Metastasis Rev 2013; 32: 163-178
24. Feuerer M, Beckhove P, Mahnke Y, et al.: Bone marrow microenvironment facilitating dendritic cell: CD4 T cell interactions and maintenance of CD4 memory. Int J Oncol 2004; 25: 867-876
25. Mazo IB, Honczarenko M, Leung H, et al.: Bone marrow is a major reservoir and site of recruitment for central memory CD8+ T cells. Immunity 2005; 22: 259-270
26. Schirrmacher V, Feuerer M, Fournier P, et al.: T-cell priming in bone marrow: the potential for long-lasting protective anti-tumor immunity. Trends Mol Med 2003; 9: 526-534
27. Khazaie K, Prifti S, Beckhove P, et al.: Persistence of dormant tumor cells in the bone marrow of tumor cell-vaccinated mice correlates with long-term immunological protection. Proc Natl Acad Sci USA 1994; 91: 7430-7434
28. Schirrmacher V, Feuerer M, Beckhove P, et al.: T cell memory, anergy and immunotherapy in breast cancer. J Mammary Gland Biol Neoplasia 2002; 7: 201-208
29. Bai L, Beckhove P, Feuerer M, et al.: Cognate interactions between memory T cells and tumor antigen-presenting dendritic cells from bone marrow of breast cancer patients: bidirectional cell stimulation, survival and antitumor activity in vivo. Int J Cancer 2003; 103: 73-83
30. Mahnke YD, Schwendemann J, Beckhove P, Schirrmacher V: Maintenance of long-term tumour-specific T-cell memory by residual dormant tumour cells. Immunology 2005; 115: 325-336
31. Solomayer EF, Feuerer M, Bai L, et al.: Influence of adjuvant hormone therapy and chemotherapy on the immune system analysed in the bone marrow of patients with breast cancer. Clin Cancer Res 2003; 9: 174-180
32. Zinkernagel RM, Bachmann MF, Kundig TM, et al.: On immunological memory. Ann Rev Immunol 1996; 14: 333-367
33. Goldrath AW, Bevan MJ: Selecting and maintaining a diverse T-cell repertoire. Nature 1999; 402: 255-262
34. Lanzavecchia A, Sallusto F: From synapses to immunological memory: the role of sustained T cell stimulation. Curr Opin Immunol 2000; 12: 92-98
35. Schuetz F, Ehlert K, Ge Y, et al.: Treatment of advanced metastasized breast cancer with bone marrow-derived tumour-reactive memory T cells: a pilot clinical study. Cancer Immunol Immunother 2009; 58: 887-900
36. Domschke C, Ge Y, Bernhardt I, et al.: Long-term survival after adoptive bone marrow T cell therapy of advanced metastasized breast cancer: follow-up analysis of a clinical pilot trial. Cancer Immunol Immunother 2013; 62: 1053-1060
37. Vesely MD, Kershaw MH, Schreiber RD, Smyth MJ: Natural innate and adaptive immunity to cancer. Ann Rev Immunol 2011; 29: 235-271
38. Zhou G, Levitsky H: Towards curative cancer immunotherapy: overcoming posttherapy tumor escape. Clin Dev Immunol 2012; 2012: 124187
39. Litzinger MT, Fernando R, Curiel TJ, et al.: IL-2 immunotoxin denileukin diftitox reduces regulatory T cells and enhances vaccine-mediated T-cell immunity. Blood 2007; 110: 3192-3201
40. Ruter J, Barnett BG, Kryczek I, et al.: Altering regulatory T cell function in cancer immunotherapy: a novel means to boost the efficacy of cancer vaccines. Front Biosc 2009; 14: 1761-1770
41. Salagianni M, Lekka E, Moustaki A, et al.: NK cell adoptive transfer combined with Ontak-mediated regulatory T cell elimination induces effective adaptive antitumor immune responses. J Immunol 2011; 186: 3327-3335
42. Beyer M, Schultze JL: Regulatory T cells in cancer. Blood 2006; 108: 804-811
43. Petrausch U, Poehlein CH, Jensen SM, et al.: Cancer immunotherapy: the role regulatory T cells play and what can be done to overcome their inhibitory effects. Curr Mol Med 2009; 9: 673-682
44. Lutsiak MEC, Semnani RT, Pascalis R, et al.: Inhibition of CD4(+)25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood 2005; 105: 2862-2868
45. Ghiringhelli F, Menard C, Puig PE, et al.: Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother 2007; 56: 641-648
46. Ge Y, Domschke C, Stoiber N, et al.: Metronomic cyclophosphamide treatment in metastasized breast cancer patients: immunological effects and clinical outcome. Cancer Immunol Immunother 2012; 61: 353-362
47. Disis ML, Bernhard H, Jaffee EM: Use of tumourresponsive T cells as cancer treatment. Lancet 2009; 373: 673-683
48. Yee C, Thompson JA, Roche P, et al.: Melanocyte destruction after antigen-specific immunotherapy of melanoma: direct evidence of t cell-mediated vitiligo. J Exp Med 2000; 192: 1637-1644
49. Dudley ME, Wunderlich JR, Yang JC, et al.: A phase I study of nonmyeloablative chemotherapy and adoptive transfer of autologous tumor antigen-specific T lymphocytes in patients with metastatic melanoma. J Immunother 2002; 25: 243-251
50. Kunert A, Straetemans T, Govers C, et al.: TCR-engineered T cells meet new challenges to treat solid tumors: choice of antigen, T cell fitness, and sensitization of tumor milieu. Front Immunol 2013; 4: 363
51. Curigliano G, Viale G, Ghioni M, et al.: Cancer-testis antigen expression in triple-negative breast cancer. Ann Oncol 2011; 22: 98-103
52. Ayyoub M, Scarlata CM, Hamai A, et al.: Expression of MAGE-A3/6 in primary breast cancer is associated with hormone receptor negative status, high histologic grade, and poor survival. J Immunother 2014; 37: 73-76
53. Katz T, Avivi I, Benyamini N, et al.: Dendritic cell cancer vaccines: from the bench to the bedside. Rambam Maimonides Med J 2014; 5:e0024
54. Ravelli A, Reuben JM, Lanza F, et al.: Immune-related strategies driving immunotherapy in breast cancer treatment: a real clinical opportunity. Expert Rev Anticancer Ther 2015; 15: 689-702
55. Feuerer M, Beckhove P, Bai L, et al.: Therapy of human tumors in NOD/SCID mice with patient-derived reactivated memory T cells from bone marrow. Nature Med 2001; 7: 452-458
56. Beckhove P, Feuerer M, Dolenc M, et al.: Specifically activated memory T cell subsets from cancer patients recognize and reject xenotransplanted autologous tumors. J Clin Invest 2004; 114: 67-76
57. Stefanovic S, Schuetz F, Sohn C, et al.: Adoptive immunotherapy of metastatic breast cancer: present and future. Cancer Metastasis Rev 2014; 33: 309-320
58. Chirgwin JM, Guise TA: Molecular mechanisms of tumor-bone interactions in osteolytic metastases. Crit Rev Eukaryot Gene Expr 2000; 10: 159-178
59. Domschke C, Schuetz F, Ge Y, et al.: Intratumoral cytokines and tumor cell biology determine spontaneous breast cancer-specific immune responses and their correlation to prognosis. Cancer Res 2009; 69: 8420-8428
60. Li MO, Wan YY, Sanjabi S, et al.: Transforming growth factor-beta regulation of immune responses. Ann Rev Immunol 2006; 24: 99-146
61. Chen W, Jin W, Hardegen N, et al.: Conversion of peripheral CD4+ CD25-naive T cells to CD4+ CD25+ regulatory T cells by TGF-beta induction of transcription factor Foxp3. J Exp Med 2003; 198: 1875-1886
62. Oelke M, Maus MV, Didiano D, et al.: Ex vivo induction and expansion of antigen-specific cytotoxic T cells by HLA-Ig-coated artificial antigen-presenting cells. Nature Med 2003; 9: 619-624
63. Chmielewski M, Abken H: CAR T cells transform to trucks: chimeric antigen receptor-redirected T cells engineered to deliver inducible IL-12 modulate the tumour stroma to combat cancer. Cancer Immunol Immunother 2012; 61: 1269-1277
64. Koehler P, Schmidt P, Hombach A, et al.: Engineered T cells for the adoptive therapy of B-cell chronic lymphocytic leukaemia. Adv Hematol 2012; 2012: 595060
65. Wu R, Forget MA, Chacon J, et al.: Adoptive T-cell therapy using autologous tumor-infiltrating lymphocytes for metastatic melanoma: current status and future outlook. Cancer J 2012; 18: 160-175
66. Ellebaek E, Iversen TZ, Junker N, et al.: Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose interleukin-2 in metastatic melanoma patients. J Transl Med 2012; 10: 169
67. Radvanyi LG, Bernatchez C, Zhang M, et al.: Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients. Clin Cancer Res 2012; 18: 6758-6770
68. Besser MJ, Shapira-Frommer R, Treves AJ, et al.: Clinical responses in a phase II study using adoptive transfer of short-term cultured tumor infiltration lymphocytes in metastatic melanoma patients. Clin Cancer Res 2010; 16: 2646-2655
69. West NR, Kost SE, Martin SD, 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 2013; 108: 155-162
70. Shi H, Liu L, Wang Z: Improving the efficacy and safety of engineered T cell therapy for cancer. Cancer Lett 2012; 328: 191-197
71. Cordova A, Toia F, La Mendola C, et al.: Characterization of human γΔ T lymphocytes infiltrating primary malignant melanomas. PloS One 2012; 7:e49878
72. Hadrup SR: The antigen specific composition of melanoma tumor infiltrating lymphocytes? Oncoimmunology 2012; 1: 935-936
73. Morgan RA, Dudley ME, Wunderlich JR, et al.: Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006; 314: 126-129
74. Johnson LA, Morgan RA, Dudley ME, et al.: Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen. Blood 2009; 114: 535-546
75. Robbins PF, Morgan RA, Feldman SA, et al.: Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol 2011; 29: 917-924
76. Yvon E, Del Vecchio M, Savoldo B, et al.: Immunotherapy of metastatic melanoma using genetically engineered GD2-specific T cells. Clin Cancer Res 2009; 15: 5852-5860
77. Lo ASY, Ma Q, Liu DL, et al.: Anti-GD3 chimeric sFv-CD28/T-cell receptor zeta designer T cells for treatment of metastatic melanoma and other neuroectodermal tumors. Clin Cancer Res 2010; 16: 2769-2780
78. Burns WR, Zhao Y, Frankel TL, et al.: A high molecular weight melanoma-associated antigen-specific chimeric antigen receptor redirects lymphocytes to target human melanomas. Cancer Res 2010; 70: 3027-3033
79. Sage PT, Francisco LM, Carman CV, et al.: The receptor PD-1 controls follicular regulatory T cells in the lymph nodes and blood. Nat Immunol 2013; 14: 152-161
80. Wimberly H, Brown JR, Schalper K, et al.: PD-L1 expression correlates with tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy in breast cancer. Cancer Immunol Res 2015; 3: 326-332
81. Nanda R, Chow LQ, Dees EC, et al. A phase Ib study of pembrolizumab (MK-3475) in patients with advanced triple-negative breast cancer. SABCS 2014; S1-09
82. Topalian SL, Sznol M, McDermott, et al.: Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol 2014; 32: 1020-1030
83. Postow MA, Chesney J, Pavlick AC, et al.: Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med 2015; 372: 2006-2017