Relevance of tumor-infiltrating lymphocytes in breast cancer (original) (raw)

1. Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2011;331:1565–70. doi: 10.1126/science.1203486. [PubMed] [CrossRef] [Google Scholar]

2. 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. doi: 10.1016/j.coi.2014.01.004. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

3. Andre F, Dieci MV, Dubsky P, Sotiriou C, Curigliano G, Denkert C, et al. Molecular pathways: involvement of immune pathways in the therapeutic response and outcome in breast cancer. Clin Cancer Res. 2013;19:28–33. doi: 10.1158/1078-0432.CCR-11-2701. [PubMed] [CrossRef] [Google Scholar]

4. Caras I, Grigorescu A, Stavaru C, Radu DL, Mogos I, Szegli G, et al. Evidence for immune defects in breast and lung cancer patients. Cancer Immunol Immunother. 2004;53:1146–52. doi: 10.1007/s00262-004-0556-2. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

5. Monjazeb AM, Zamora AE, Grossenbacher SK, Mirsoian A, Sckisel GD, Murphy WJ. Immunoediting and antigen loss: overcoming the Achilles heel of immunotherapy with antigen non-specific therapies. Front Oncol. 2013;3:197. doi: 10.3389/fonc.2013.00197. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

6. Enderling H, Hlatky L, Hahnfeldt P. Immunoediting: evidence of the multifaceted role of the immune system in self-metastatic tumor growth. Theor Biol Med Model. 2012;9:31. doi: 10.1186/1742-4682-9-31. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

7. Vesely MD, Schreiber RD. Cancer immunoediting: antigens, mechanisms, and implications to cancer immunotherapy. Ann N Y Acad Sci. 2013;1284:1–5. doi: 10.1111/nyas.12105. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

8. Quezada SA, Peggs KS, Simpson TR, Allison JP. Shifting the equilibrium in cancer immunoediting: from tumor tolerance to eradication. Immunol Rev. 2011;241:104–18. doi: 10.1111/j.1600-065X.2011.01007.x. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

9. Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD. Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol. 2002;3:991–8. doi: 10.1038/ni1102-991. [PubMed] [CrossRef] [Google Scholar]

10. O’Sullivan T, Saddawi-Konefka R, Vermi W, Koebel CM, Arthur C, White JM, et al. Cancer immunoediting by the innate immune system in the absence of adaptive immunity. J Exp Med. 2012;209:1869–82. doi: 10.1084/jem.20112738. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

11. Emens LA. Breast cancer immunobiology driving immunotherapy: vaccines and immune checkpoint blockade. Expert Rev Anticancer Ther. 2012;12:1597–611. doi: 10.1586/era.12.147. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

12. Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012;12:252–64. doi: 10.1038/nrc3239. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

14. van Elsas A, Hurwitz AA, Allison JP. Combination immunotherapy of B16 melanoma using anti-cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and granulocyte/macrophage colony-stimulating factor (GM-CSF)-producing vaccines induces rejection of subcutaneous and metastatic tumors accompanied by autoimmune depigmentation. J Exp Med. 1999;190:355–66. doi: 10.1084/jem.190.3.355. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

15. Fan X, Quezada SA, Sepulveda MA, Sharma P, Allison JP. Engagement of the ICOS pathway markedly enhances efficacy of CTLA-4 blockade in cancer immunotherapy. J Exp Med. 2014;211:715–25. doi: 10.1084/jem.20130590. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

16. Kim K, Skora AD, Li Z, Liu Q, Tam AJ, Blosser RL, et al. Eradication of metastatic mouse cancers resistant to immune checkpoint blockade by suppression of myeloid-derived cells. Proc Natl Acad Sci U S A. 2014;111:11774–9. doi: 10.1073/pnas.1410626111. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

17. Pentcheva-Hoang T, Simpson TR, Montalvo-Ortiz W, Allison JP. Cytotoxic T lymphocyte antigen-4 blockade enhances antitumor immunity by stimulating melanoma-specific T-cell motility. Cancer Immunol Res. 2014;2:970–80. doi: 10.1158/2326-6066.CIR-14-0104. [PubMed] [CrossRef] [Google Scholar]

18. Brahmer JR, Drake CG, Wollner I, Powderly JD, Picus J, Sharfman WH, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol. 2010;28:3167–75. doi: 10.1200/JCO.2009.26.7609. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

19. Wolchok JD, Neyns B, Linette G, Negrier S, Lutzky J, Thomas L, et al. Ipilimumab monotherapy in patients with pretreated advanced melanoma: a randomised, double-blind, multicentre, phase 2, dose-ranging study. Lancet Oncol. 2010;11:155–64. doi: 10.1016/S1470-2045(09)70334-1. [PubMed] [CrossRef] [Google Scholar]

20. Postow MA, Callahan MK, Wolchok JD. Immune checkpoint blockade in cancer therapy. J Clin Oncol. 2015;33:1974–198. doi: 10.1200/JCO.2014.59.4358. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

21. Beavis PA, Divisekera U, Paget C, Chow MT, John LB, Devaud C, et al. Blockade of A2A receptors potently suppresses the metastasis of CD73+ tumors. Proc Natl Acad Sci U S A. 2013;110:14711–6. doi: 10.1073/pnas.1308209110. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

22. Beavis PA, Milenkovski N, Henderson MA, John LB, Allard B, Loi S, et al. Adenosine receptor 2A blockade increases the efficacy of anti-PD-1 through enhanced antitumor t-cell responses. Cancer Immunol Res. 2015;3:506–17. doi: 10.1158/2326-6066.CIR-14-0211. [PubMed] [CrossRef] [Google Scholar]

23. Beavis PA, Stagg J, Darcy PK, Smyth MJ. CD73: a potent suppressor of antitumor immune responses. Trends Immunol. 2012;33:231–7. doi: 10.1016/j.it.2012.02.009. [PubMed] [CrossRef] [Google Scholar]

24. Waickman AT, Alme A, Senaldi L, Zarek PE, Horton M, Powell JD. Enhancement of tumor immunotherapy by deletion of the A2A adenosine receptor. Cancer Immunol Immunother. 2012;61:917–26. doi: 10.1007/s00262-011-1155-7. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

25. Ohta A, Gorelik E, Prasad SJ, Ronchese F, Lukashev D, Wong MK, et al. A2A adenosine receptor protects tumors from antitumor T cells. Proc Natl Acad Sci U S A. 2006;103:13132–7. doi: 10.1073/pnas.0605251103. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

26. Nishikawa H, Sakaguchi S. Regulatory T cells in cancer immunotherapy. Curr Opin Immunol. 2014;27:1–7. doi: 10.1016/j.coi.2013.12.005. [PubMed] [CrossRef] [Google Scholar]

27. Zheng X, Koropatnick J, Chen D, Velenosi T, Ling H, Zhang X, et al. Silencing IDO in dendritic cells: a novel approach to enhance cancer immunotherapy in a murine breast cancer model. Int J Cancer. 2013;132:967–77. doi: 10.1002/ijc.27710. [PubMed] [CrossRef] [Google Scholar]

28. Holmgaard RB, Zamarin D, Munn DH, Wolchok JD, Allison JP. Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4. J Exp Med. 2013;210:1389–402. doi: 10.1084/jem.20130066. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

29. Holtzhausen A, Zhao F, Evans KS, Hanks BA. Early carcinogenesis involves the establishment of immune privilege via intrinsic and extrinsic regulation of indoleamine 2,3-dioxygenase-1: translational implications in cancer immunotherapy. Front Immunol. 2014;5:438. doi: 10.3389/fimmu.2014.00438. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

30. Platten M, von Knebel DN, Oezen I, Wick W, Ochs K. Cancer immunotherapy by targeting IDO1/TDO and their downstream effectors. Front Immunol. 2014;5:673. [PMC free article] [PubMed] [Google Scholar]

31. Wang Z, Shi X, Li Y, Fan J, Zeng X, Xian Z, et al. Blocking autophagy enhanced cytotoxicity induced by recombinant human arginase in triple-negative breast cancer cells. Cell Death Dis. 2014;5 doi: 10.1038/cddis.2014.503. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

32. Bedoya AM, Tate DJ, Baena A, Cordoba CM, Borrero M, Pareja R, et al. Immunosuppression in cervical cancer with special reference to arginase activity. Gynecol Oncol. 2014;135:74–80. doi: 10.1016/j.ygyno.2014.07.096. [PubMed] [CrossRef] [Google Scholar]

33. Vasquez-Dunddel D, Pan F, Zeng Q, Gorbounov M, Albesiano E, Fu J, et al. STAT3 regulates arginase-I in myeloid-derived suppressor cells from cancer patients. J Clin Invest. 2013;123:1580–9. doi: 10.1172/JCI60083. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

34. Ghansah T. A novel strategy for modulation of MDSC to enhance cancer immunotherapy. Oncoimmunology. 2012;1:984–5. doi: 10.4161/onci.20201. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

35. Forghani P, Khorramizadeh MR, Waller EK. Silibinin inhibits accumulation of myeloid-derived suppressor cells and tumor growth of murine breast cancer. Cancer Med. 2014;3:215–24. doi: 10.1002/cam4.186. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

36. Markowitz J, Wesolowski R, Papenfuss T, Brooks TR, Carson WE., 3rd Myeloid-derived suppressor cells in breast cancer. Breast Cancer Res Treat. 2013;140:13–21. doi: 10.1007/s10549-013-2618-7. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

37. Ono M, Tsuda H, Shimizu C, Yamamoto S, Shibata T, Yamamoto H, 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. doi: 10.1007/s10549-011-1554-7. [PubMed] [CrossRef] [Google Scholar]

38. West NR, Milne K, Truong PT, Macpherson N, Nelson BH, Watson PH. Tumor-infiltrating lymphocytes predict response to anthracycline-based chemotherapy in estrogen receptor-negative breast cancer. Breast Cancer Res. 2011;13:R126. doi: 10.1186/bcr3072. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

39. Loi S, Sirtaine N, Piette F, Salgado R, Viale G, Van Eenoo F, 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;31:860–7. doi: 10.1200/JCO.2011.41.0902. [PubMed] [CrossRef] [Google Scholar]

40. Wimberly H, Brown JR, Schalper KA, Haack H, Silver MR, Nixon C, et al. PD-L1 expression correlates with tumor-infiltrating lymphocytes and response to neoadjuvant chemotherapy in breast cancer. Cancer Immunol Res. 2014;3:326–32. doi: 10.1158/2326-6066.CIR-14-0133. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

41. Denkert C, von Minckwitz G, Brase JC, Sinn BV, Gade S, Kronenwett R, 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;33:983–91. doi: 10.1200/JCO.2014.58.1967. [PubMed] [CrossRef] [Google Scholar]

42. Ghiringhelli F, Larmonier N, Schmitt E, Parcellier A, Cathelin D, Garrido C, et al. CD4+CD25+ regulatory T cells suppress tumor immunity but are sensitive to cyclophosphamide which allows immunotherapy of established tumors to be curative. Eur J Immunol. 2004;34:336–44. doi: 10.1002/eji.200324181. [PubMed] [CrossRef] [Google Scholar]

43. Zitvogel L, Apetoh L, Ghiringhelli F, Kroemer G. Immunological aspects of cancer chemotherapy. Nat Rev Immunol. 2008;8:59–73. doi: 10.1038/nri2216. [PubMed] [CrossRef] [Google Scholar]

44. Ghiringhelli F, Apetoh L. The interplay between the immune system and chemotherapy: emerging methods for optimizing therapy. Expert Rev Clin Immunol. 2014;10:19–30. doi: 10.1586/1744666X.2014.865520. [PubMed] [CrossRef] [Google Scholar]

45. Ghiringhelli F, Apetoh L, Tesniere A, Aymeric L, Ma Y, Ortiz C, et al. Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors. Nat Med. 2009;15:1170–8. doi: 10.1038/nm.2028. [PubMed] [CrossRef] [Google Scholar]

46. Apetoh L, Ghiringhelli F, Tesniere A, Obeid M, Ortiz C, Criollo A, et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy. Nat Med. 2007;13:1050–9. doi: 10.1038/nm1622. [PubMed] [CrossRef] [Google Scholar]

47. Nowak AK, Robinson BW, Lake RA. Gemcitabine exerts a selective effect on the humoral immune response: implications for combination chemo-immunotherapy. Cancer Res. 2002;62:2353–8. [PubMed] [Google Scholar]

48. Tongu M, Harashima N, Monma H, Inao T, Yamada T, Kawauchi H, et al. Metronomic chemotherapy with low-dose cyclophosphamide plus gemcitabine can induce anti-tumor T cell immunity in vivo. Cancer Immunol Immunother. 2013;62:383–91. doi: 10.1007/s00262-012-1343-0. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

49. Homma Y, Taniguchi K, Nakazawa M, Matsuyama R, Mori R, Takeda K, et al. Changes in the immune cell population and cell proliferation in peripheral blood after gemcitabine-based chemotherapy for pancreatic cancer. Clin Transl Oncol. 2014;16:330–5. doi: 10.1007/s12094-013-1079-0. [PubMed] [CrossRef] [Google Scholar]

50. Mozaffari F, Lindemalm C, Choudhury A, Granstam-Bjorneklett H, Lekander M, Nilsson B, et al. Systemic immune effects of adjuvant chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide and/or radiotherapy in breast cancer: a longitudinal study. Cancer Immunol Immunother. 2009;58:111–20. doi: 10.1007/s00262-008-0530-5. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

51. Lutsiak ME, Semnani RT, De Pascalis R, Kashmiri SV, Schlom J, Sabzevari H. Inhibition of CD4(+)25+ T regulatory cell function implicated in enhanced immune response by low-dose cyclophosphamide. Blood. 2005;105:2862–8. doi: 10.1182/blood-2004-06-2410. [PubMed] [CrossRef] [Google Scholar]

52. Zhu Y, Liu N, Xiong SD, Zheng YJ, Chu YW. CD4+Foxp3+ regulatory T-cell impairment by paclitaxel is independent of toll-like receptor 4. Scand J Immunol. 2011;73:301–8. doi: 10.1111/j.1365-3083.2011.02514.x. [PubMed] [CrossRef] [Google Scholar]

53. Machiels JP, Reilly RT, Emens LA, Ercolini AM, Lei RY, Weintraub D, et al. 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 Res. 2001;61:3689–97. [PubMed] [Google Scholar]

54. Park JY, Jang MJ, Chung YH, Kim KY, Kim SS, Lee WB, et al. Doxorubicin enhances CD4(+) T-cell immune responses by inducing expression of CD40 ligand and 4-1BB. Int Immunopharmacol. 2009;9:1530–9. doi: 10.1016/j.intimp.2009.09.008. [PubMed] [CrossRef] [Google Scholar]

55. Hannesdottir L, Tymoszuk P, Parajuli N, Wasmer MH, Philipp S, Daschil N, et al. Lapatinib and doxorubicin enhance the Stat1-dependent antitumor immune response. Eur J Immunol. 2013;43:2718–29. doi: 10.1002/eji.201242505. [PubMed] [CrossRef] [Google Scholar]

56. Nowak AK, Lake RA, Marzo AL, Scott B, Heath WR, Collins EJ, et al. Induction of tumor cell apoptosis in vivo increases tumor antigen cross-presentation, cross-priming rather than cross-tolerizing host tumor-specific CD8 T cells. J Immunol. 2003;170:4905–13. doi: 10.4049/jimmunol.170.10.4905. [PubMed] [CrossRef] [Google Scholar]

57. Kroemer G, Galluzzi L, Kepp O, Zitvogel L. Immunogenic cell death in cancer therapy. Annu Rev Immunol. 2013;31:51–72. doi: 10.1146/annurev-immunol-032712-100008. [PubMed] [CrossRef] [Google Scholar]

58. Menard S, Tomasic G, Casalini P, Balsari A, Pilotti S, Cascinelli N, et al. Lymphoid infiltration as a prognostic variable for early-onset breast carcinomas. Clin Cancer Res. 1997;3:817–9. [PubMed] [Google Scholar]

59. Denkert C, Loibl S, Noske A, Roller M, Muller BM, Komor M, et al. Tumor-associated lymphocytes as an independent predictor of response to neoadjuvant chemotherapy in breast cancer. J Clin Oncol. 2010;28:105–13. doi: 10.1200/JCO.2009.23.7370. [PubMed] [CrossRef] [Google Scholar]

60. Ladoire S, Arnould L, Apetoh L, Coudert B, Martin F, Chauffert B, et al. Pathologic complete response to neoadjuvant chemotherapy of breast carcinoma is associated with the disappearance of tumor-infiltrating foxp3+ regulatory T cells. Clin Cancer Res. 2008;14:2413–20. doi: 10.1158/1078-0432.CCR-07-4491. [PubMed] [CrossRef] [Google Scholar]

61. Ignatiadis M, Singhal SK, Desmedt C, Haibe-Kains B, Criscitiello C, Andre F, et al. Gene modules and response to neoadjuvant chemotherapy in breast cancer subtypes: a pooled analysis. J Clin Oncol. 2012;30:1996–2004. doi: 10.1200/JCO.2011.39.5624. [PubMed] [CrossRef] [Google Scholar]

62. Yu H, Yang J, Jiao S, Li Y, Zhang W, Wang J. T-box transcription factor 21 expression in breast cancer and its relationship with prognosis. Int J Clin Exp Pathol. 2014;7:6906–13. [PMC free article] [PubMed] [Google Scholar]

63. Issa-Nummer Y, Darb-Esfahani S, Loibl S, Kunz G, Nekljudova V, Schrader I, et al. Prospective validation of immunological infiltrate for prediction of response to neoadjuvant chemotherapy in HER2-negative breast cancer--a substudy of the neoadjuvant GeparQuinto trial. PLoS One. 2013;8 doi: 10.1371/journal.pone.0079775. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

64. Dieci MV, Criscitiello C, Goubar A, Viale G, Conte P, Guarneri V, et al. Prognostic value of tumor-infiltrating lymphocytes on residual disease after primary chemotherapy for triple-negative breast cancer: a retrospective multicenter study. Ann Oncol. 2014;25:611–8. doi: 10.1093/annonc/mdt556. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

65. Loi S, Michiels S, Salgado R, Sirtaine N, Jose V, Fumagalli D, 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. 2014;25:1544–50. doi: 10.1093/annonc/mdu112. [PubMed] [CrossRef] [Google Scholar]

66. Adams S, Gray RJ, Demaria S, Goldstein L, Perez EA, Shulman LN, 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;32:2959–66. doi: 10.1200/JCO.2013.55.0491. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

67. Gennari R, Menard S, Fagnoni F, Ponchio L, Scelsi M, Tagliabue E, et al. Pilot study of the mechanism of action of preoperative trastuzumab in patients with primary operable breast tumors overexpressing HER2. Clin Cancer Res. 2004;10:5650–5. doi: 10.1158/1078-0432.CCR-04-0225. [PubMed] [CrossRef] [Google Scholar]

68. Salgado R, Denkert C, Campbell C, Savas P, Nucifero P, Aura C, 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. JAMA Oncol. 2015;1:448–54. doi: 10.1001/jamaoncol.2015.0830. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

69. Arnould L, Gelly M, Penault-Llorca F, Benoit L, Bonnetain F, Migeon C, et al. Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism? Br J Cancer. 2006;94:259–67. doi: 10.1038/sj.bjc.6602930. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

70. Bianchini G, Gianni L. The immune system and response to HER2-targeted treatment in breast cancer. Lancet Oncol. 2014;15:e58–68. doi: 10.1016/S1470-2045(13)70477-7. [PubMed] [CrossRef] [Google Scholar]

71. Oda N, Shimazu K, Naoi Y, Morimoto K, Shimomura A, Shimoda M, et al. Intratumoral regulatory T cells as an independent predictive factor for pathological complete response to neoadjuvant paclitaxel followed by 5-FU/epirubicin/cyclophosphamide in breast cancer patients. Breast Cancer Res Treat. 2012;136:107–16. doi: 10.1007/s10549-012-2245-8. [PubMed] [CrossRef] [Google Scholar]

72. Seo AN, Lee HJ, Kim EJ, Kim HJ, Jang MH, Lee HE, et al. Tumour-infiltrating CD8+ lymphocytes as an independent predictive factor for pathological complete response to primary systemic therapy in breast cancer. Br J Cancer. 2013;109:2705–13. doi: 10.1038/bjc.2013.634. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

73. Lee HJ, Seo JY, Ahn JH, Ahn SH, Gong G. Tumor-associated lymphocytes predict response to neoadjuvant chemotherapy in breast cancer patients. J Breast Cancer. 2013;16:32–9. doi: 10.4048/jbc.2013.16.1.32. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

74. Brown JR, Wimberly H, Lannin DR, Nixon C, Rimm DL, Bossuyt V. Multiplexed quantitative analysis of CD3, CD8, and CD20 predicts response to neoadjuvant chemotherapy in breast cancer. Clin Cancer Res. 2014;20:5995–6005. doi: 10.1158/1078-0432.CCR-14-1622. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

75. Mahmoud S, Paish E, Powe D, Macmillan R, Grainge M, Lee A, et al. Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol. 2011;29:1949–55. doi: 10.1200/JCO.2010.30.5037. [PubMed] [CrossRef] [Google Scholar]

76. West NR, Kost SE, Martin SD, Milne K, Deleeuw RJ, Nelson BH, 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;108:155–62. doi: 10.1038/bjc.2012.524. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

77. Aruga T, Suzuki E, Saji S, Horiguchi S, Horiguchi K, Sekine S, et al. A low number of tumor-infiltrating FOXP3-positive cells during primary systemic chemotherapy correlates with favorable anti-tumor response in patients with breast cancer. Oncol Rep. 2009;22:273–8. [PubMed] [Google Scholar]

78. Ladoire S, Mignot G, Dabakuyo S, Arnould L, Apetoh L, Rebe C, et al. In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival. J Pathol. 2011;224:389–400. doi: 10.1002/path.2866. [PubMed] [CrossRef] [Google Scholar]

79. Liu F, Li Y, Ren M, Zhang X, Guo X, Lang R, et al. Peritumoral FOXP3(+) regulatory T cell is sensitive to chemotherapy while intratumoral FOXP3(+) regulatory T cell is prognostic predictor of breast cancer patients. Breast Cancer Res Treat. 2012;135:459–67. doi: 10.1007/s10549-012-2132-3. [PubMed] [CrossRef] [Google Scholar]

80. Ruffell B, Au A, Rugo HS, Esserman LJ, Hwang ES, Coussens LM. Leukocyte composition of human breast cancer. Proc Natl Acad Sci U S A. 2012;109:2796–801. doi: 10.1073/pnas.1104303108. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

81. Gu-Trantien C, Loi S, Garaud S, Equeter C, Libin M, de Wind A, et al. CD4(+) follicular helper T cell infiltration predicts breast cancer survival. J Clin Invest. 2013;123:2873–92. doi: 10.1172/JCI67428. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

82. Ma C, Zhang Q, Ye J, Wang F, Zhang Y, Wevers E, et al. Tumor-infiltrating gammadelta T lymphocytes predict clinical outcome in human breast cancer. J Immunol. 2012;189:5029–36. doi: 10.4049/jimmunol.1201892. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

83. Mattarollo SR, Kenna T, Nieda M, Nicol AJ. Chemotherapy and zoledronate sensitize solid tumour cells to Vgamma9Vdelta2 T cell cytotoxicity. Cancer Immunol Immunother. 2007;56:1285–97. doi: 10.1007/s00262-007-0279-2. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

84. Kobayashi H, Tanaka Y, Yagi J, Osaka Y, Nakazawa H, Uchiyama T, et al. Safety profile and anti-tumor effects of adoptive immunotherapy using gamma-delta T cells against advanced renal cell carcinoma: a pilot study. Cancer Immunol Immunother. 2007;56:469–76. doi: 10.1007/s00262-006-0199-6. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

85. Yang L, Qi Y, Hu J, Tang L, Zhao S, Shan B. Expression of Th17 cells in breast cancer tissue and its association with clinical parameters. Cell Biochem Biophys. 2012;62:153–9. doi: 10.1007/s12013-011-9276-3. [PubMed] [CrossRef] [Google Scholar]

86. Verma C, Eremin JM, Robins A, Bennett AJ, Cowley GP, El-Sheemy MA, et al. Abnormal T regulatory cells (Tregs: FOXP3+, CTLA-4+), myeloid-derived suppressor cells (MDSCs: monocytic, granulocytic) and polarised T helper cell profiles (Th1, Th2, Th17) in women with large and locally advanced breast cancers undergoing neoadjuvant chemotherapy (NAC) and surgery: failure of abolition of abnormal treg profile with treatment and correlation of treg levels with pathological response to NAC. J Transl Med. 2013;11:16. doi: 10.1186/1479-5876-11-16. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

87. Demaria S, Volm MD, Shapiro RL, Yee HT, Oratz R, Formenti SC, et al. Development of tumor-infiltrating lymphocytes in breast cancer after neoadjuvant paclitaxel chemotherapy. Clin Cancer Res. 2001;7:3025–30. [PubMed] [Google Scholar]

88. Ercolini AM, Ladle BH, Manning EA, Pfannenstiel LW, Armstrong TD, Machiels JP, et al. Recruitment of latent pools of high-avidity CD8(+) T cells to the antitumor immune response. J Exp Med. 2005;201:1591–602. doi: 10.1084/jem.20042167. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

89. Simpson TR, Li F, Montalvo-Ortiz W, Sepulveda MA, Bergerhoff K, Arce F, et al. Fc-dependent depletion of tumor-infiltrating regulatory T cells co-defines the efficacy of anti-CTLA-4 therapy against melanoma. J Exp Med. 2013;210:1695–710. doi: 10.1084/jem.20130579. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

90. DeNardo DG, Brennan DJ, Rexhepaj E, Ruffell B, Shiao SL, Madden SF, et al. Leukocyte complexity predicts breast cancer survival and functionally regulates response to chemotherapy. Cancer Discov. 2011;1:54–67. doi: 10.1158/2159-8274.CD-10-0028. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

91. Alistar A, Chou J, Nagalla S, Black M, DAgostino R, Miller L. Dual roles for immune metagenes in breast cancer prognosis and therapy prediction. Genome Med. 2014;6:80. doi: 10.1186/s13073-014-0080-8. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

92. Schalper KA, Velcheti V, Carvajal D, Wimberly H, Brown J, Pusztai L, et al. In situ tumor PD-L1 mRNA expression is associated with increased TILs and better outcome in breast carcinomas. Clin Cancer Res. 2014;20:2773–82. doi: 10.1158/1078-0432.CCR-13-2702. [PubMed] [CrossRef] [Google Scholar]

93. Muenst S, Schaerli AR, Gao F, Daster S, Trella E, Droeser RA, et al. Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat. 2014;146:15–24. doi: 10.1007/s10549-014-2988-5. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

94. Muenst S, Soysal SD, Gao F, Obermann EC, Oertli D, Gillanders WE. The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat. 2013;139:667–76. doi: 10.1007/s10549-013-2581-3. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

95. Sun S, Fei X, Mao Y, Wang X, Garfield DH, Huang O, et al. PD-1(+) immune cell infiltration inversely correlates with survival of operable breast cancer patients. Cancer Immunol Immunother. 2014;63:395–406. doi: 10.1007/s00262-014-1519-x. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

96. Taube JM, Klein AP, Brahmer JR, Xu H, Pan X, Kim JH, et al. Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy. Clin Cancer Res. 2014;20:5064. doi: 10.1158/1078-0432.CCR-13-3271. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

97. Rahbar R, Lin A, Ghazarian M, Yau HL, Paramathas S, Lang PA, et al. B7-h4 expression by nonhematopoietic cells in the tumor microenvironment promotes antitumor immunity. Cancer Immunol Res. 2015;3:184–95. doi: 10.1158/2326-6066.CIR-14-0113. [PubMed] [CrossRef] [Google Scholar]

98. Sica GL, Choi IH, Zhu G, Tamada K, Wang SD, Tamura H, et al. B7-H4, a molecule of the B7 family, negatively regulates T cell immunity. Immunity. 2003;18:849–61. doi: 10.1016/S1074-7613(03)00152-3. [PubMed] [CrossRef] [Google Scholar]

99. Zang X, Loke P, Kim J, Murphy K, Waitz R, Allison JP. B7x: a widely expressed B7 family member that inhibits T cell activation. Proc Natl Acad Sci U S A. 2003;100:10388–92. doi: 10.1073/pnas.1434299100. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

100. Lu L, Xu X, Zhang B, Zhang R, Ji H, Wang X. Combined PD-1 blockade and GITR triggering induce a potent antitumor immunity in murine cancer models and synergizes with chemotherapeutic drugs. J Transl Med. 2014;12:36. doi: 10.1186/1479-5876-12-36. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

101. Lesterhuis WJ, Salmons J, Nowak AK, Rozali EN, Khong A, Dick IM, et al. Synergistic effect of CTLA-4 blockade and cancer chemotherapy in the induction of anti-tumor immunity. PLoS One. 2013;8 doi: 10.1371/journal.pone.0061895. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

102. Verbrugge I, Hagekyriakou J, Sharp LL, Galli M, West A, McLaughlin NM, et al. Radiotherapy increases the permissiveness of established mammary tumors to rejection by immunomodulatory antibodies. Cancer Res. 2012;72:3163–74. doi: 10.1158/0008-5472.CAN-12-0210. [PubMed] [CrossRef] [Google Scholar]

103. Twyman-Saint Victor C, Rech AJ, Maity A, Rengan R, Pauken KE, Stelekati E, et al. Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature. 2015;520:373–7. doi: 10.1038/nature14292. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

104. Liu L, Mayes PA, Eastman S, Shi H, Yadavilli S, Zhang T, et al. The BRAF and MEK inhibitors dabrafenib and trametinib: effects on immune function and in combination with immunomodulatory antibodies targeting PD-1, PD-L1, and CTLA-4. Clin Cancer Res. 2015;21:1639. doi: 10.1158/1078-0432.CCR-14-2339. [PubMed] [CrossRef] [Google Scholar]

105. Callahan MK, Masters G, Pratilas CA, Ariyan C, Katz J, Kitano S, et al. Paradoxical activation of T cells via augmented ERK signaling mediated by a RAF inhibitor. Cancer Immunol Res. 2014;2:70–9. doi: 10.1158/2326-6066.CIR-13-0160. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

106. Lee SJ, Myers L, Muralimohan G, Dai J, Qiao Y, Li Z, et al. 4-1BB and OX40 dual costimulation synergistically stimulate primary specific CD8 T cells for robust effector function. J Immunol. 2004;173:3002–12. doi: 10.4049/jimmunol.173.5.3002. [PubMed] [CrossRef] [Google Scholar]

107. Gray JC, French RR, James S, Al-Shamkhani A, Johnson PW, Glennie MJ. Optimising anti-tumour CD8 T-cell responses using combinations of immunomodulatory antibodies. Eur J Immunol. 2008;38:2499–511. doi: 10.1002/eji.200838208. [PubMed] [CrossRef] [Google Scholar]

108. Morales-Kastresana A, Sanmamed MF, Rodriguez I, Palazon A, Martinez-Forero I, Labiano S, et al. Combined immunostimulatory monoclonal antibodies extend survival in an aggressive transgenic hepatocellular carcinoma mouse model. Clin Cancer Res. 2013;19:6151–62. doi: 10.1158/1078-0432.CCR-13-1189. [PubMed] [CrossRef] [Google Scholar]

109. Cuadros C, Dominguez AL, Lollini PL, Croft M, Mittler RS, Borgstrom P, et al. Vaccination with dendritic cells pulsed with apoptotic tumors in combination with anti-OX40 and anti-4-1BB monoclonal antibodies induces T cell-mediated protective immunity in Her-2/neu transgenic mice. Int J Cancer. 2005;116:934–43. doi: 10.1002/ijc.21098. [PubMed] [CrossRef] [Google Scholar]

110. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, et al. Patterns of somatic mutation in human cancer genomes. Nature. 2007;446:153–8. doi: 10.1038/nature05610. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

111. Krauthammer M, Kong Y, Ha BH, Evans P, Bacchiocchi A, McCusker JP, et al. Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma. Nat Genet. 2012;44:1006–14. doi: 10.1038/ng.2359. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

112. Wood LD, Parsons DW, Jones S, Lin J, Sjoblom T, Leary RJ, et al. The genomic landscapes of human breast and colorectal cancers. Science. 2007;318:1108–13. doi: 10.1126/science.1145720. [PubMed] [CrossRef] [Google Scholar]

113. Marshall NA, Galvin KC, Corcoran AM, Boon L, Higgs R, Mills KH. Immunotherapy with PI3K inhibitor and Toll-like receptor agonist induces IFN-gamma+IL-17+ polyfunctional T cells that mediate rejection of murine tumors. Cancer Res. 2012;72:581–91. doi: 10.1158/0008-5472.CAN-11-0307. [PubMed] [CrossRef] [Google Scholar]

114. Dudley ME, Gross CA, Somerville RP, Hong Y, Schaub NP, Rosati SF, et al. Randomized selection design trial evaluating CD8+−enriched versus unselected tumor-infiltrating lymphocytes for adoptive cell therapy for patients with melanoma. J Clin Oncol. 2013;31:2152–9. doi: 10.1200/JCO.2012.46.6441. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

115. Chacon JA, Wu RC, Sukhumalchandra P, Molldrem JJ, Sarnaik A, Pilon-Thomas S, et al. Co-stimulation through 4-1BB/CD137 improves the expansion and function of CD8(+) melanoma tumor-infiltrating lymphocytes for adoptive T-cell therapy. PLoS One. 2013;8 doi: 10.1371/journal.pone.0060031. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

116. Kodumudi KN, Weber A, Sarnaik AA, Pilon-Thomas S. Blockade of myeloid-derived suppressor cells after induction of lymphopenia improves adoptive T cell therapy in a murine model of melanoma. J Immunol. 2012;189:5147–54. doi: 10.4049/jimmunol.1200274. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

117. Radvanyi LG, Bernatchez C, Zhang M, Fox PS, Miller P, Chacon J, 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;18:6758–70. doi: 10.1158/1078-0432.CCR-12-1177. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

118. Kershaw MH, Westwood JA, Darcy PK. Gene-engineered T cells for cancer therapy. Nat Rev Cancer. 2013;13:525–41. doi: 10.1038/nrc3565. [PubMed] [CrossRef] [Google Scholar]

119. Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371:1507–17. doi: 10.1056/NEJMoa1407222. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

120. Koya RC, Mok S, Otte N, Blacketor KJ, Comin-Anduix B, Tumeh PC, et al. BRAF inhibitor vemurafenib improves the antitumor activity of adoptive cell immunotherapy. Cancer Res. 2012;72:3928–37. doi: 10.1158/0008-5472.CAN-11-2837. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

121. John LB, Devaud C, Duong CP, Yong CS, Beavis PA, Haynes NM, et al. Anti-PD-1 antibody therapy potently enhances the eradication of established tumors by gene-modified T cells. Clin Cancer Res. 2013;19:5636–46. doi: 10.1158/1078-0432.CCR-13-0458. [PubMed] [CrossRef] [Google Scholar]

122. Ahmed N, Brawley VS, Hegde M, Robertson C, Ghazi A, Gerken C, et al. Human epidermal growth factor receptor 2 (HER2)-specific chimeric antigen receptor-modified T cells for the immunotherapy of HER2-positive sarcoma. J Clin Oncol. 2015;33:1688. doi: 10.1200/JCO.2014.58.0225. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

123. Ishikawa T, Adachi S, Okayama T, Kokura S, Mizushima K, Doi T, et al. Cytotoxic T lymphocyte-associated antigen 4 inhibition increases the antitumor activity of adoptive T-cell therapy when carried out with naive rather than differentiated T cells. Oncol Rep. 2015;33:2545. [PubMed] [Google Scholar]

124. Salgado R, Denkert C, Demaria S, Sirtaine N, Klauschen F, Pruneri G, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015;26:259–71. doi: 10.1093/annonc/mdu450. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

125. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet. 2014;384:164–72. doi: 10.1016/S0140-6736(13)62422-8. [PubMed] [CrossRef] [Google Scholar]

126. Ko HJ, Kim YJ, Kim YS, Chang WS, Ko SY, Chang SY, et al. A combination of chemoimmunotherapies can efficiently break self-tolerance and induce antitumor immunity in a tolerogenic murine tumor model. Cancer Res. 2007;67:7477–86. doi: 10.1158/0008-5472.CAN-06-4639. [PubMed] [CrossRef] [Google Scholar]

127. Fridlender ZG, Sun J, Singhal S, Kapoor V, Cheng G, Suzuki E, et al. Chemotherapy delivered after viral immunogene therapy augments antitumor efficacy via multiple immune-mediated mechanisms. Mol Ther. 2010;18:1947–59. doi: 10.1038/mt.2010.159. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

128. Suzuki E, Kapoor V, Jassar AS, Kaiser LR, Albelda SM. Gemcitabine selectively eliminates splenic Gr-1+/CD11b+ myeloid suppressor cells in tumor-bearing animals and enhances antitumor immune activity. Clin Cancer Res. 2005;11:6713–21. doi: 10.1158/1078-0432.CCR-05-0883. [PubMed] [CrossRef] [Google Scholar]

129. Schiavoni G, Sistigu A, Valentini M, Mattei F, Sestili P, Spadaro F, et al. Cyclophosphamide synergizes with type I interferons through systemic dendritic cell reactivation and induction of immunogenic tumor apoptosis. Cancer Res. 2011;71:768–78. doi: 10.1158/0008-5472.CAN-10-2788. [PubMed] [CrossRef] [Google Scholar]

130. Xu W, Cai J, Li S, Zhang H, Han J, Wen M, et al. Improving the in vivo persistence, distribution and function of cytotoxic T lymphocytes by inhibiting the tumor immunosuppressive microenvironment. Scand J Immunol. 2013;78:50–60. doi: 10.1111/sji.12065. [PubMed] [CrossRef] [Google Scholar]

131. Umansky V, Sevko A. Overcoming immunosuppression in the melanoma microenvironment induced by chronic inflammation. Cancer Immunol Immunother. 2012;61:275–82. doi: 10.1007/s00262-011-1164-6. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

132. Zhang L, Dermawan K, Jin M, Liu R, Zheng H, Xu L, et al. Differential impairment of regulatory T cells rather than effector T cells by paclitaxel-based chemotherapy. Clin Immunol. 2008;129:219–29. doi: 10.1016/j.clim.2008.07.013. [PubMed] [CrossRef] [Google Scholar]

133. Ma Y, Adjemian S, Mattarollo SR, Yamazaki T, Aymeric L, Yang H, et al. Anticancer chemotherapy-induced intratumoral recruitment and differentiation of antigen-presenting cells. Immunity. 2013;38:729–41. doi: 10.1016/j.immuni.2013.03.003. [PubMed] [CrossRef] [Google Scholar]

134. Alizadeh D, Trad M, Hanke NT, Larmonier CB, Janikashvili N, Bonnotte B, et al. Doxorubicin eliminates myeloid-derived suppressor cells and enhances the efficacy of adoptive T-cell transfer in breast cancer. Cancer Res. 2014;74:104–18. doi: 10.1158/0008-5472.CAN-13-1545. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

135. Tesniere A, Schlemmer F, Boige V, Kepp O, Martins I, Ghiringhelli F, et al. Immunogenic death of colon cancer cells treated with oxaliplatin. Oncogene. 2010;29:482–91. doi: 10.1038/onc.2009.356. [PubMed] [CrossRef] [Google Scholar]

136. Kang TH, Mao CP, Lee SY, Chen A, Lee JH, Kim TW, et al. Chemotherapy acts as an adjuvant to convert the tumor microenvironment into a highly permissive state for vaccination-induced antitumor immunity. Cancer Res. 2013;73:2493–504. doi: 10.1158/0008-5472.CAN-12-4241. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

137. Guo ZS, Hong JA, Irvine KR, Chen GA, Spiess PJ, Liu Y, et al. De novo induction of a cancer/testis antigen by 5-aza-2′-deoxycytidine augments adoptive immunotherapy in a murine tumor model. Cancer Res. 2006;66:1105–13. doi: 10.1158/0008-5472.CAN-05-3020. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

138. Mikyskova R, Indrova M, Vlkova V, Bieblova J, Simova J, Parackova Z, et al. DNA demethylating agent 5-azacytidine inhibits myeloid-derived suppressor cells induced by tumor growth and cyclophosphamide treatment. J Leukoc Biol. 2014; in press. [PubMed]

139. Hornychova H, Melichar B, Tomsova M, Mergancova J, Urminska H, Ryska A. Tumor-infiltrating lymphocytes predict response to neoadjuvant chemotherapy in patients with breast carcinoma. Cancer Invest. 2008;26:1024–31. doi: 10.1080/07357900802098165. [PubMed] [CrossRef] [Google Scholar]

140. Liu S, Lachapelle J, Leung S, Gao D, Foulkes WD, Nielsen TO. CD8+ lymphocyte infiltration is an independent favorable prognostic indicator in basal-like breast cancer. Breast Cancer Res. 2012;14:R48. doi: 10.1186/bcr3148. [PMC free article] [PubMed] [CrossRef] [Google Scholar]

141. Yamaguchi R, Tanaka M, Yano A, Tse GM, Yamaguchi M, Koura K, et al. Tumor-infiltrating lymphocytes are important pathologic predictors for neoadjuvant chemotherapy in patients with breast cancer. Hum Pathol. 2012;43:1688–94. doi: 10.1016/j.humpath.2011.12.013. [PubMed] [CrossRef] [Google Scholar]

142. Ali HR, Provenzano E, Dawson SJ, Blows FM, Liu B, Shah M, et al. Association between CD8+ T-cell infiltration and breast cancer survival in 12,439 patients. Ann Oncol. 2014;25:1536–43. doi: 10.1093/annonc/mdu191. [PubMed] [CrossRef] [Google Scholar]

143. Nabholtz JM, Abrial C, Mouret-Reynier MA, Dauplat MM, Weber B, Gligorov J, et al. Multicentric neoadjuvant phase II study of panitumumab combined with an anthracycline/taxane-based chemotherapy in operable triple-negative breast cancer: identification of biologically defined signatures predicting treatment impact. Ann Oncol. 2014;25:1570–7. doi: 10.1093/annonc/mdu183. [PubMed] [CrossRef] [Google Scholar]