Immune blockade inhibition in breast cancer

Anticancer Research

Volumn 36, Issue 11, 2016, Pages 5607-5622

  Voutsadakis, Ioannis A ^a  

^a Sault Area Hospitals   (Canada)

Author keywords

Biomarkers; Breast cancer; Checkpoint inhibition; CTLA 4; Immune blockade; PD 1; PD L1; Review; Tumor infiltrating lymphocytes

Indexed keywords

PROGRAMMED DEATH 1 LIGAND 1; TUMOR MARKER;

BREAST CANCER; CANCER CELL; CANCER INHIBITION; CANCER PROGNOSIS; GENOMIC INSTABILITY; HUMAN; IMMUNOCOMPETENT CELL; PRIORITY JOURNAL; REVIEW; TUMOR ASSOCIATED LEUKOCYTE; BREAST NEOPLASMS; FEMALE; IMMUNOLOGY; PROGNOSIS;

BREAST NEOPLASMS; FEMALE; HUMANS; LYMPHOCYTES, TUMOR-INFILTRATING; PROGNOSIS;

EID: 84993939802     PISSN: 02507005     EISSN: 17917530     Source Type: Journal    
DOI: 10.21873/anticanres.11145     Document Type: Review

References (114)

1. Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, Castiglione M, Tu D, Shepherd LE, Pritchard KI, Livingston RB, Davidson NE, Norton L, Perez EA, Abrams JS, Therasse P, Palmer MJ and Pater JL: A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med 349: 1793-1802, 2003.
2. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, Baselga J and Norton L: Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344: 783-792, 2001.
3. Romond EH, Perez EA, Bryant J, Suman VJ, Geyer CE, Davidson NE, Tan-Chiu E, Martino S, Paik S, Kaufman PA, Swain SM, Pisansky TM, Fehrenbacher L, Kutteh LA, Vogel VG, Visscher DW, Yothers G, Jenkins RB, Brown AM, Dakhil SR, Mamounas EP, Lingle WL, Klein PM, Ingle JN and Wolmark N: Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353: 1673-1684, 2005.
4. Goss PE, Ingle JN, Pritchard KI, Robert NJ, Muss H, Gralow J, Gelmon K, Whelan T, Strasser-Weippl K, Rubin S, Sturtz K, Wolff AC, Winer E, Hudis C, Stopeck A, Beck JT, Kaur JS, Whelan K, Tu D and Parulekar WR: Extending aromatase-inhibitor adjuvant therapy to 10 years. N Engl J Med 375: 209-219, 2016.
5. Verma S, Miles D, Gianni L, Krop IE, Welslau M, Baselga J, Pegram M, Oh DY, Diéras V, Guardino E, Fang L, Lu MW, Olsen S, Blackwell K and EMILIA Study Group: Trastuzumab emtansine for HER2-positive advanced breast cancer. N Engl J Med 368: 1783-1791, 2013.
6. Burstein MD, Tsimelzon A, Poage GM, Covington KR, Contreras A, Fuqua SAW, Savage MI, Osborne CK, Hilsenbeck SG, Chang JC, Mills GB, Lau CC and Brown PH: Comprehensive genomic analysis identifies novel subtypes and targets of triple-negative breast cancer. Clin Cancer Res 21: 1688-1698, 2015.
7. Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y and Pietenpol JA: Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 121: 2750-2767, 2011.
8. Tutt A, Robson M, Garber JE, Domchek SM, Audeh MW, Weitzel JN, Friedlander M, Arun B, Loman N, Schmutzler RK, Wardley A, Mitchell G, Earl H, Wickens M and Carmichael J: Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet 376: 235-244, 2010.
9. Dustin ML: The immunological synapse. Cancer Immunol Res 2: 1023-1033, 2014.
10. Sigal LH: Basic science for the clinician 55: CTLA-4. J Clin Rheumatol 18: 155-158, 2012.
11. Ward FJ, Dahal LN, Wijesekera SK, Abdul-Jawad SK, Kaewarpai T, Xu H, Vickers MA and Barker RN: The soluble isoform of CTLA-4 as a regulator of T-cell responses. Eur J Immunol 43: 1274-1285, 2013.
12. Khalil DN, Smith EL, Brentjens RJ and Wolchok JD: The future of cancer treatment: immunomodulation, CARs and combination immunotherapy. Nat Rev Clin Oncol xx: 1-18, 2016.
13. Yu H, Yang J, Jiao S, Li Y, Zhang W and Wang J: Cytotoxic T lymphocyte antigen 4 expression in human breast cancer: implications for prognosis. Cancer Immunol Immunother 64: 853-860, 2015.
14. Contardi E, Palmisano GL, Tazzari PL, Martelli AM, Falà F, Fabbi M, Kato T, Lucarelli E, Donati D, Polito L, Bolognesi A, Ricci F, Salvi S, Gargaglione V, Mantero S, Alberghini M, Battista Ferrara G and Pia Pistillo M: CTLA-4 is constitutively expressed on tumor cells and can trigger apoptosis upon ligand interaction. Int J Cancer 117: 538-550, 2005.
15. Jaberipour M, Habibagahi M, Hosseini A, Rezai Habibabad S, Talei A and Ghaderi A: Increased CTLA-4 and FOXP3 transcripts in peripheral blood mononuclear cells of patients with breast cancer. Pathol Oncol Res 16: 547-551, 2010.
16. Erfani N, Razmkhah M and Ghaderi A: Circulating soluble CTLA4 (sCTLA4) is elevated in patients with breast cancer. Cancer Invest 28: 828-832, 2010.
17. Schalper KA, Velcheti V, Carvajal D, Wimberly H, Brown J, Pusztai L and Rimm DL: In situ tumor PD-L1 mRNA expression is associated with increased TILs and better outcome in breast carcinomas. Clin Cancer Res 20: 2773-2782, 2014.
18. Sabatier R, Finetti P, Mamessier E, Adelaide J, Chaffanet M, Raza Ali H, Viens P, Caldas C, Birnbaum D and Bertucci F: Prognostic and predictive value of PDL1 expression in breast cancer. Oncotarget 6: 5449-5464, 2014.
19. Barrett MT, Anderson KS, Lenkiewicz E, Andreozzi M, Cunliffe HE, Klassen CL, Dueck AC, McCullough AE, Reddy SK, Ramanathan RK, Northfelt DW and Pockaj BA: Genomic amplification of 9p24.1 targeting JAK2, PD-L1, and PD-L2 is enriched in high-risk triple-negative breast cancer. Oncotarget 6: 26483-26493, 2015.
20. Michaut M, Chin S-F, Majewski I, Severson TM, Bismeijer T, de Koning L, Peeters JK, Schouten PC, Rueda OM, Bosma AJ, Tarrant F, Fan Y, He B, Xue Z, Mittempergher L, Kluin RJC, Heijmans J, Snel M, Pereira B, Schlicker A, Provenzano E, Raza Ali H, Gaber A, O'Hurley G, Lehn S, Muris JJF, Wesseling J, Kay E, Sammut SJ, Bardwell HA, Barbet AS, Bard F, Lecerf C, O'Connor DP, Vis DJ, Benes CH, McDermott U, Garnett MJ, Simon IM, Jirström K, Dubois T, Linn SC, Gallagher WM, Wessels LFA, Caldas C and Bernards R: Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer. Sci Rep 6: 18517, 2016.
21. Ali HR, Glont S-E, Blows FM, Provenzano E, Dawson S-J, Liu B, Hiller L, Dunn J, Poole CJ, Bowden S, Earl HM, Pharoah PDP and Caldas C: PD-L1 protein expression in breast cancer is rare, enriched in basal-like tumours and associated with infiltrating lymphocytes. Ann Oncol 26: 1488-1493, 2015.
22. Mittendorf EA, Philips AV, Meric-Bernstam F, Qiao N, Wu Y, Harrington S, Su X, Wang Y, Gonzalez-Angulo AM, Akcakanat A, Chawla A, Curran M, Hwu P, Sharma P, Litton JK, Molldrem JJ and Alatrash G: PD-L1 expression in triple-negative breast cancer. Cancer Immunol Res 2: 361-370, 2014.
23. Ghebeh H, Mohammed S, Al-Omair A, Qattan A, Lehe C, Al-Qudaihi G, Elkum N, Alshabanah M, Bin Amer S, Tulbah A, Ajarim D, Al-Tweigeri T and Dermime S: The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: Correlation with important high-risk prognostic factors. Neoplasia 8: 190-198, 2006.
24. Muenst S, Schaerli AR, Gao F, Däster S, Trella E, Droeser RA, Muraro MG, Zajac P, Zanetti R, Gillanders WE, Weber WP and Soysal SD: Expression of programmed death ligand 1 (PD-L1) is associated with poor prognosis in human breast cancer. Breast Cancer Res Treat 146: 15-24, 2014.
25. Qin T, Zeng Y, Qin G, Xu F, Lu J, Fang W, Xue C, Zhan J, Zhang X, Zheng Q, Peng R, Yuan Z, Zhang L and Wang S: High PD-L1 expression was associated with poor prognosis in 870 Chinese patients with breast cancer. Oncotarget 6: 33972-33981, 2015.
26. Baptista MZ, Sarian LO, Derchain SFM, Pinto GA and Vassallo J: Prognostic significance of PD-L1 and PD-L2 in breast cancer. Hum Pathol 47: 78-84, 2016.
27. Mazel M, Jacot W, Pantel K, Bartkowiak K, Topart D, Cayrefourcq L, Rossille D, Maudelonde T, Fest T and Alix-Panabières C: Frequent expression of PD-L1 on circulating breast cancer cells. Mol Oncol 9: 1773-1782, 2015.
28. Kawaguchi K, Suzuki E, Yamaguchi A, Yamamoto M, Morita S and Toi M: Altered expression of major immune regulatory molecules in peripheral blood immune cells associated with breast cancer. Breast Cancer [Epub ahead of print], 2016.
29. Muenst S, Soysal SD, Gao F, Obermann EC, Oertli D and 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 139: 667-676, 2013.
30. Loi S, Drubay D, Adams S, Francis PAA, Joensuu H, Dieci MV, Badve S, Demaria S, Gray R, Piccart MJJ, Kellokumpa-Lehtinen P-L, Andre F, Dufaure-Gare I, Denkert C, Salgado R and Michiels S: Pooled individual patient data analysis of stromal tumor infiltrating lymphocytes in primary triple-negative breast cancer treated with anthracycline-based chemotherapy. San Antonio Breast Cancer Symposium S1-03, 2015.
31. Ibrahim EM, Al-Foheidi ME, Al-Mansour MM and Kazkaz GA: The prognostic value of tumor-infiltrating lymphocytes in triple-negative breast cancer: a meta-analysis. Breast Cancer Res Treat 148: 467-476, 2014.
32. Loi S, Michiels S, Salgado R, Sirtaine N, Jose V, Fumagalli D, Kellokumpu-Lehtinen P-L, Bono P, Kataja V, Desmedt C, Piccart MJ, Loibl S, Denkert C, Smyth MJ, Joensuu H and Sotiriou C: 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: 1544-1550, 2014.
33. Hida AI, Sagara Y, Yotsumoto D, Kanemitsu S, Kawano J, Baba S, Rai Y, Oshiro Y, Aogi K, Sagara S and Ohi Y: Prognostic and predictive impacts of tumor infiltrating lymphocytes differ between triple-negative and HER2-positive breast cancers treated with standard systemic therapies. Breast Cancer Res Treat 158: 1-9, 2016.
34. Mao Y, Qu Q, Zhang Y, Liu J, Chen X and Shen K: The value of Tumor Infiltrating Lymphocytes (TILs) for predicting response to neoadjuvant chemotherapy in breast cancer: A systematic review and meta-analysis. PLoS one 9: e115103, 2014.
35. Bianchini G, Pusztai L, Pienkowski T, Im Y-H, Bianchi G V, Tseng L-M, Liu M-C, Lluch A, Galeota E, Magazzù D, de la Haba-Rodríguez J, Oh D-Y, Poirier B, Pedrini JL, Semiglazov V, Valagussa P and Gianni L: Immune modulation of pathologic complete response after neoadjuvant HER2-directed therapies in the NeoSphere trial. Ann Oncol 26: 2429-2436, 2015.
36. Issa-Nummer Y, Darb-Esfahani S, Loibl S, Kunz G, Nekljudova V, Schrader I, Valentin Sinn B, Ulmer H-U, Kronenwett R, Just M, Kühn T, Diebold K, Untch M, Holms F, Blohmer J-U, Habeck J-O, Dietel M, Overkamp F, Krabisch P, von Minckwitz G and Denkert C: 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 8: e79775, 2013.
37. Nabholtz JM, Abrial C, Mouret-Reynier MA, Dauplat MM, Weber B, Gligorov J, Forest AM, Tredan O, Vanlemmens L, Petit T, Guiu S, Van Praagh I, Jouannaud C, Dubray-Longeras P, Tubiana-Mathieu N, Benmammar KE, Kullab S, Bahadoor MRK, Radosevic-Robin N, Kwiatkowski F, Desrichard A, Cayre A, Uhrhammer N, Chalabi N, Chollet P and Penault-Llorca F: Multicenter 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 25: 1570-1577, 2014.
38. Wimberly H, Brown JR, Schalper K, Haack H, Silver MR, Nixon C, Bossuyt V, Pusztai L, Lannin DR and Pimm DL: PD-L1 expression correlates with Tumor-Infiltrating Lymphocytes and response to neoadjuvant chemotherapy in breast cancer. Cancer Immunol Res 3: 326-332, 2015.
39. Kim ST, Jeong H, Woo OH, Seo JH, Kim A, Lee ES, Shin SW, Kim YH, Kim JS and Park KH: Tumor-infiltrating lymphocytes, tumor characteristics, and recurrence in patients with early breast cancer. Am J Clin Oncol 36: 224-231, 2013.
40. Mahmoud SMA, Paish EC, Powe DG, Macmillan RD, Lee AHS, Ellis IO and Green AR: An evaluation of the clinical significance of FOXP+ infiltrating cells in human breast cancer. Breast Cancer Res Treat 127: 99-108, 2011.
41. Rech AJ, Mick R, Kaplan DE, Chang K-M, Domchek SM and Vonderheide RH: Homeostasis of peripheral FoxP3+ CD4+ regulatory T cells in patients with early and late stage breast cancer. Cancer Immunol Immunother 59: 599-607, 2010.
42. Verma C, Eremin JM, Robins A, Bennett AJ, Cowley GP, El-Sheemy MA, Jibril JA and Eremin O: Abnormal T regulatory cells (Tregs: FOXP3+, CTLA-4+), myeloid-derived suppressor cells (MDSCs: monocytic, granulocytic) and polarized 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 11: 16, 2013.
43. Mahmoud SMA, Lee AHS, Paish EC, Macmillan RD, Ellis IO and Green AR: The prognostic significance of B lymphocytes in invasive carcinoma of the breast. Breast Cancer Res Treat 132: 545-553, 2012.
44. Mahmoud SMA, Claire Paish E, Powe DG, Macmillan RD, Grainge MJ, Lee AHS, Ellis IO and Green AR: Tumor-Infiltrating CD8+ Lymphocytes predict clinical outcome in breast cancer. J Clin Oncol 29: 1949-1955, 2011.
45. Savas P, Salgado R, Denkert C, Sotiriou C, Darcy PK, Smyth MJ and Loi S: Clinical relevance of host immunity in breast cancer: from TILs to the clinic. Nat Rev Clin Oncol 13: 228-241, 2016.
46. Gubin MM, Zhang X, Schuster H, Caron E, Ward JP, Noguchi T, Ivanova Y, Hundal J, Arthur CD, Krebber W-J, Mulder GE, Toebes M, Vesely MD, Lam SSK, Korman AJ, Allison JP, Freeman GJ, Sharpe AH, Pearce EL, Schumacher TN, Aebersold R, Rammensee H-G, Melief CJM, Mardis ER, Gillanders WE, Artyomov MN and Schreiber RD: Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens. Nature 515: 577-581, 2014.
47. Yadav M, Jhunjhunwala S, Phung QT, Lupardus P, Tanguay J, Bumbaca S, Franci C, Cheung TK, Fritsche J, Weinschenk T, Modrusan Z, Mellman I, Lill JR and Delamarre L: Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature 515: 572-576, 2014.
48. Xiao Y and Freeman GJ: The Microsatellite Instable (MSI) subset of colorectal cancer is a particularly good candidate for checkpoint blockade immunotherapy. Cancer Discov 5: 16-18, 2015.
49. Smyrk TC, Watson P, Kaul K and Lynch HT: Tumor-infiltrating lymphocytes are a marker for microsatellite instability in colorectal carcinoma. Cancer 91: 2417-2422, 2001.
50. Llosa NJ, Cruise M, Tam A, Wicks EC, Hechenbleikner EM, Taube JM, Blosser RL, Fan H, Wang H, Luber BS, Zhang M, Papadopoulos N, Kinzler KW, Vogelstein B, Sears CL, Anders RA, Pardoll DM and Housseau F: The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov 5: 43-51, 2015.
51. Le DT, Uram JN, Wang H, Bartlett BR, Kemberling H, Eyring AD, Skora AD, Luber BS, Azad NS, Laheru D, Biedrzycki B, Donehower RC, Zaheer A, Fisher GA, Crocenzi TS, Lee JJ, Duffy SM, Goldberg RM, de la Chapelle A, Koshiji M, Bhaijee F, Huebner T, Hruban RH, Wood LD, Cuka N, Pardoll DM, Papadopoulos N, Kinzler KW, Zhou S, Cornish TC, Taube JM, Anders RA, Eshleman JR, Vogelstein B and Diaz Jr LA: PD-1 blockade in tumors with mismatch-repair deficiency. N Engl J Med 372: 2509-2520, 2015.
52. Dudley JC, Lin MT, Le DT and Eshleman JR: Microsatellite instability as a biomarker for PD-1 blockade. Clin Cancer Res 22: 813-820, 2016.
53. Adem C, Soderberg CL, Cunningham JM, Reynolds C, Sebo TJ, Thibodeau SN, Hartmann LC and Jenkins RB: Microsatellite instability in hereditary and sporadic breast cancers. Int J Cancer 107: 580-582, 2003.
54. Lawrence MS, Stojanov P, Polak P, Kryukov GV, Cibulskis K, Sivachenko A, Carter SL, Stewart C, Mermel CH, Roberts SA, Kiezun A, Hammerman PS, McKenna A, Drier Y, Zou L, Ramos AH, Pugh TJ, Stransky N, Helman E, Kim J, Sougnez C, Ambrogio L, Nickerson E, Shefler E, Cortés ML, Auclair D, Saksena G, Voet D, Noble M, DiCara D, Lin P, Lichtenstein L, Heiman DI, Fennell T, Imielinski M, Hernandez B, Hodis E, Baca S, Dulak AM, Lohr J, Landau D-A, Wu CJ, Melendez-Zajgla J, Hidalgo-Miranda A, Koren A, McCarroll SA, Mora J, Lee RS, Crompton B, Onofrio R, Parkin M, Winckler W, Ardlie K, Gabriel SB, Roberts CWM, Biegel JA, Stegmaier K, Bass AJ, Garraway LA, Meyerson M, Golub TR, Gordenin DA, Sunyaev S, Lander ES and Getz G: Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature 499: 214-218, 2013.
55. Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, Leiserson MDM, Miller CA, Welch JS, Walter MJ, Wendl MC, Ley TJ, Wilson RK, Raphael BJ and Ding L: Mutational landscap and significance across 12 major cancer types. Nature 502: 333-339, 2013.
56. Segal NH, Parsons DW, Peggs KS, Velculescu V, Kinzler KW, Vogelstein B and Allison JP: Epitope landscape in breast and colorectal cancer. Cancer Res 68: 889-892, 2008.
57. Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky JM, Desrichard A, Walsh LA, Postow MA, Wong P, Ho TS, Hollmann TJ, Bruggerman C, Kannan K, Li Y, Elipenahli C, Liu C, Harbison CT, Wang L, Ribas A, Wolchok JD and Chan TA: Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med 371: 2189-2199, 2014.
58. low tumor cells is regulated by γδ T and NK cells during the early steps of tumor growth. Cancer Immunity 9: 10, 2009.
59. Forero A, Li Y, Chen D, Grizzle WE, Updike KL, Merz ND, Downs-Kelly E, Burwell TC, Vaklavas C, Buchsbaum DJ, Myers RM, LoBuglio AF and Varley KE: 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 4: 390-399, 2016.
60. Kmieciak M, Worschech A, Nikizad H, Gowda M, Habibi M, Depcrynski A, Wang E, Godder K, Holt SE, Marincola FM and Manjili MH: CD+ T cells inhibit the neu-specific CD8+ T-cell exhaustion during the priming phase of immune responses against breast cancer. Breast Cancer Res Treat 126: 385-394, 2011.
61. Erdag G, Schaefer JT, Smolkin ME, Deacon DH, Shea SM, Dengel LT, Patterson JW and Slingluff Jr CL: Immunotype and immunohistologic characteristics of tumor-infiltrating immune cells are associated with clinical outcome in metastatic melanoma. Cancer Res 72: 1070-1080, 2012.
62. Wang Q, Li S-H, Wang H, Xiao Y, Sahin O, Brady SW, Li P, Ge H, Jaffee EM, Muller WJ, Hortobagyi GN and Yu D: Concomitant targeting of tumor cells and induction of T-cell response synergizes to effectively inhibit trastuzumab-resistant breast cancer. Cancer Res 72: 4417-4428, 2012.
63. Loi S, Dushyanthen S, Beavis PA, Salgado R, Denkert C, Savas P, Combs S, Rimm DL, Giltnane JM, Estrada MV, Sánchez V, Sanders ME, Cook RS, Pilkinton MA, Mallal SA, Wang K, Miller VA, Stephens PJ, Yelensky R, Doimi FD, Gómez H, Ryzhov SV, Darcy PK, Arteaga CL and Balko JM: 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: 1499-1509, 2015.
64. Ota K, Azuma K, Kawahara A, Hattori S, Iwama E, Tanizaki J, Harada T, Matsumoto K, Takayama K, Takamori S, Kage M, Hoshino T, Nakanishi Y and Okamoto I: Induction of PD-L1 expression by the EML4-ALK oncoprotein and downstream signaling pathways in non-small cell lung cancer. Clin Cancer Res 21: 4014-4021, 2015.
65. Casey SC, Tong L, Li Y, Do R, Walz S, Fitzgerald KN, Gouw AM, Baylot V, Gütgemann I, Eilers M and Felsher DW: MYC regulates the antitumor immune response through CD47 and PD-L1. Science 352: 227-231, 2016.
66. Zhang P, Su D-M, Liang M and Fu J: Chemopreventive agents induce programmed death-1-ligand (PD-L1) surface expression in breast cancer cells and promote PD-L1 mediated T cell apoptosis. Mol Immunol 45: 1470-1476, 2008.
67. Soliman H, Khalil F and Antonia S: PD-L1 expression is increased in a subset of basal type breast cancer cells. PLoS ONE 9: e88557, 2014.
68. Cortez MA, Ivan C, Valdecanas D, Wang X, Peltier HJ, Ye Y, Araujo L, Carbone DP, Shilo K, Giri DK, Kelnar K, Martin D, Komaki R, Gomez DR, Krishnan S, Calin GA, Bader AG and Welsh JW: PDL1 regulation by p53 via miR-34. J Natl Cancer Inst 108: djv303, 2016.
69. Chen L, Gibbons DL, Goswami S, Cortez MA, Ahn Y-H, Byers LA, Zhang X, Yi X, Dwyer D, Lin W, Diao L, Wang J, Roybal JD, Patel M, Ungewiss C, Peng D, Antonia S, Mediavilla-Varela M, Robertson G, Jones S, Suraokar M, Welsh JW, Erez B, Wistuba II, Chen L, Peng D, Wang S, Ullrich SE, Heymach JV, Kurie JM and Qin FX-F: Metastasis is regulated via microRNA-200/ZEB1 axis control of tumour cell PD-L1 expression and intratumoral immunosuppression. Nat Commun 5: 5241, 2014.
70. Teng MWL, Foong Ngiow S, Ribas A and Smyth MJ: Classifying cancers based on T-cell infiltration and PD-L1. Cancer Res 75: 2139-2145, 2015.
71. Pico de Coaña Y, Choudhury A and Kiessling R: Checkpoint blockade for cancer therapy: revitalizing a suppressed immune system. Trends Mol Med 21: 482-491, 2015.
72. Simeone E, Genticore G, Giannarelli D, Grimaldi AM, Caracò C, Curvietto M, Esposito A, Paone M, Palla M, Cavalcanti E, Sandomenico F, Petrillo A, Botti G, Fulciniti F, Palmieri G, Queirolo P, Marchetti P, Ferraresi V, Rinaldi G, Pistillo MP, Ciliberto G, Mozzillo N and Ascierto PA: Immunological and biological changes during ipilimumab treatment and their potential correlation with clinical response and survival in patients with advanced melanoma. Cancer Immunol Immunother 63: 675-683, 2014.
73. Kelderman S, Heemskerk B, van Tinteren H, van den Brom RR, Hospers GA, van den Eertwegh AJ, Kapiteijn EW, de Groot JW, Soetekouw P, Jansen RL, Fiets E, Furness AJ, Renn A, Krzystanek M, Szallasi Z, Lorigan P, Gore ME, Schumacher TN, Haanen JB, Larkin JM and Blank CU: Lactate dehydrogenase as a selection criterion for ipilimumab treatment in metastatic melanoma. Cancer Immunol Immunother 63: 449-458, 2014.
74. van Akkooi ACJ, Atkins MB, Agarwala SS and Lorigan P: Surgical management and adjuvant therapy for high-risk and metastatic melanoma. Am Soc Clin Oncol Ed Book 35: e505-e514, 2016.
75. Eggermont AM, Chiarion-Sileni V, Grob JJ, Dummer R, Wolchok JD, Schmidt H, Hamid O, Robert C, Ascierto PA, Richards JM, Lebbé C, Ferraresi V, Smylie M, Weber JS, Maio M, Konto C, Hoos A, de Pril V, Gurunath RK, de Schaetzen G, Suciu S and Testori A: Adjuvant ipilimumab versus placebo after complete resection of high-risk stage III melanoma (EORTC 18071): a randomized, double-blind, phase 3 trial. Lancet Oncol 16: 522-530, 2015.
76. Borghaei H, Paz-Ares L, Horn L, Spigel DR, Steins M, Ready NE, Chow LQ, Vokes EE, Felip E, Holgado E, Barlesi F, Kohlhäufl M, Arrieta O, Burgio MA, Fayette J, Lena H, Poddubskaya E, Gerber DE, Gettinger SN, Rudin CM, Rizvi N, Crinò L, Blumenschein Jr GR, Antonia SJ, Dorange C, Harbison CT, Graf Finckenstein F and Brahmer JR: Nivolumab versus docetaxel in advanced nonsquamous Non-Small-Cell Lung Cancer. N Engl J Med 373: 1627-1639, 2015.
77. Brahmer J, Reckamp KL, Baas P, Crinò L, Eberhardt WEE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holdado E, Waterhouse D, Ready N, Gainor J, Arén Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B and Spigel DR: Nivolumab versus docetaxel in advanced squamous-cell Non-Small-Cell Lung Cancer. N Engl J Med 373: 123-135, 2015.
78. Robert C, Long GV, Brady B, Dutriaux C, Maio M, Mortier L, Hassel JC, Rutkowski P, McNeil C, Kalinka-Warzocha E, Savage KJ, Hernberg MM, Lebbé C, Charles J, Mihalcioiu C, Chiarion-Sileni V, Mauch C, Cognetti F, Arance A, Schmidt H, Schadendorf D, Gogas H, Lundgren-Eriksson L, Horak C, Sharkey B, Waxman IM, Atkinson V, and Ascierto PA: Nivolumab in previously untreated melanoma without BRAF mutation. N Engl J Med 372: 320-330, 2015.
79. Motzer RJ, Escudier B, McDermott DF, George S, Hammers HJ, Srinivas S, Tykodi SS, Sosman JA, Procopio G, Plimack ER, Castellano D, Choueiri TK, Gurney H, Donskov F, Bono P, Wagstaff J, Gauler TC, Ueda T, Tomita Y, Schutz FA, Kollmannsberger C, Larkin J, Ravaud A, Simon JS, Xu L-A, Waxman IM, and Sharma P, for the CheckMate 025 Investigators: Nivolumab versus everolimus in advanced renal-cell carcinoma. N Engl J Med 373: 1803-1813, 2015.
80. Garon EB, Rizvi NA, Hui R, Leighl N, Balmanoukian AS, Eder JP, Patnaik A, Aggarwal C, Gubens M, Horn L, Carcereny E, Ahn M-J, Felip E, Lee J-S, Hellmann MD, Hamid O, Goldman JW, Soria J-C, Dolled-Filhart M, Rutledge RZ, Zhang J, Lunceford JK, Rangwala R, Lubiniecki GM, Roach C, Emancipator K and Gandhi L for the KEYNOTE-001 Investigators: Pembrolizumab for the treatment of Non-Small-Cell Lung Cancer. N Engl JMed 372: 2018-2028, 2015.
81. Powles T, Eder JP, Fine GD, Braiteh FS, Loriot Y, Cruz C, Bellmunt J, Burris HA, Petrylak DP, Teng S-l, Shen X, Boyd Z, Hegde PS, Chen DS and Vogelzang NJ: MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 515: 558-562, 2014.
82. Muro K, Chung HC, Shankaran V, Geva R, Catenacci D, Gupta S, Eder JP, Golan T, Le DT, Burtness B, McRee AJ, Lin C-C, Pathiraja K, Lunceford J, Emancipator K, Juco J, Koshiji M and Bang Y-J: Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial. Lancet Oncol 17: 717-726, 2016.
83. Antonia SJ, López-Martin JA, Bendell J, Ott PA, Taylor M, Eder JP, Jäger D, Pietanza MC, Le DT, de Braud F, Morse MA, Ascierto PA, Horn L, Amin A, Pillai RN, Evans J, Chau I, Bono P, Atmaca A, Sharma P, Harbison CT, Lin C-S, Christensen O and Calvo E: Nivolumabalone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial. Lancet Oncol 17: 883-895, 2016.
84. Nghiem PT, Bhatia S, Lipson EJ, Kudchadkar RR, Miller NJ, Annamalai L, Berry S, Chartash EK, Daud A, Fling SP, Friedlander PA, Kluger HM, Kohrt HE, Lundgren L, Margolin K, Mitchell A, Olencki T, Pardoll DM, Reddy SA, Shantha EM, Sharfman WH, Sharon E, Shemanski LR, Shinohara MM, Sunshine JC, Taube JM, Thompson JA, Townson SM, Yearley JH, Topalian SL and Cheever MA: PD-1 blockade with pembrolizumab in advanced Merkel-cell carcinoma. N Engl JMed 374: 2542-2552, 2016.
85. Vonderheide RH, LoRusso PM, Khalil M, Gartner EM, Khaira D, Soulieres D, Dorazio P, Trosko JA, Rüter J, Mariani GL, Usari T and Domchek SM: Tremelimumab in combination with exemestane in patients with advanced breast cancer and treatment-associated modulation of inducible costimulatory expression on patient T cells. Clin Cancer Res 16: 3485-3494, 2010.
86. Rugo HS, Delord J-P, Im S-A, Ott PA, Piha-Paul SAA, Bedard PL, Sachdev J, Le Tourneau C, van Brummelen E, Varga A, Saraf S, Pietrangelo D, Karantza V and Tan A: Preliminary efficacy and safety of pembrolizumab (MK-34750) in patients with PD-L1-positive, estrogen receptor-positive (ER+)/HER2-negative advanced breast cancer enrolled in KEYNOTE-028. San Antonio Breast Cancer Symposium S5-07, 2015.
87. Nanda R, Chow LQM, Dees EC, Berger R, Gupta S, Geva R, Pusztai L, Pathiraja K, Aktan G, Cheng JD, Karantza V and Buisseret L: Pembrolizumab in patients with advanced triple-negative breast cancer: Phase Ib KEYNOTE -012 study. J Clin Oncol 34: 2460-2467, 2016.
88. Dirix LY, Takacs I, Nikolinakos P, Jerusalem G, Arkenau H-T, Hamilton EP, von Heydebreck A, Grote H-J, Chin K and Lippman ME: Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: A phase Ib JAVELIN solid tumor trial. San Antonio Breast Cancer Symposium S1-04, 2015.
89. Gibson J: Anti-PD-L1 for metastatic triple-negative breast cancer. Lancet Oncol 16: e264, 2015.
90. Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, Linette GP, Meyer N, Giguere JK, Agarwala SS, Shaheen M, Ernstoff MS, Minor D, Salama AK, Taylor M, Ott PA, Rollin LM, Horak C, Gagnier P, Wolchok JD and Hodi FS: Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med 372: 2006-2017, 2015.
91. Curran MA, Montalvo W, Yagita H and Allison JP: PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci USA 107: 4275-4280, 2010.
92. Beavis PA, Milenkovski N, Henderson MA, John LB, Allard B, Loi S, Kershaw MH, Stagg J and Darcy PK: Adenosine Receptor 2A blockade increases the efficacy of anti-PD-1 through enhanced antitumor T-cell responses. Cancer Immunol Res 3: 506-517, 2015.
93. Allard B, Pommey S, Smyth MJ and Stagg J: Targeting CD73 enhances the antitumor activity of anti-PD-1 and anti-CTLA-4 mAbs. Clin Cancer Res 19: 5626-5635, 2013.
94. Hauser RA, Olanow CW, Kieburtz KD, Pourcher E, Docu-Axelerad A, Lew M, Kozyolkin O, Neale A, Resburg C, Meya U, Kenney C and Bandak S: Tozadenant (SYN115) in patients with Parkinson's disease who have motor fluctuations on levodopa: a phase 2b, double-blind, randomized trial. Lancet Neurol 13: 767-776, 2014.
95. Loi S, Pommey S, Haibe-Kains B, Beavis PA, Darcy PK, Smyth MJ and Stagg J: CD73 promotes anthracycline resistance and poor prognosis in triple-negative breast cancer. Proc Natl Acad Sci USA 110: 11091-11096, 2013.
96. Beavis PA, Slaney CY, Milenkovski N, Henderson MA, Loi S, Stagg J, Kershaw MH and Darcy PK: CD73: A potential biomarker for anti-PD-1 therapy. OncoImmunol 4: e1046675, 2015.
97. Müller P, Kreuzaler M, Khan T, Thommen DS, Martin K, Glatz K, Savic S, Harbeck N, Nitz U, Gluz O, von Bergwelt-Baildon M, Kreipe H, Reddy S, Christgen M and Zippelius A: Trastuzumab emtansine (T-DM1) renders HER+ breast cancer highly susceptible to CTLA-4/PD-1 blockade. Sci Transl Med 7: 315ra188, 2015.
98. + T cells by modulating cholesterol metabolism. Nature 531: 651-655, 2016.
99. Emans L, Adams S, Loi S, Schmid P, Schneeweiss A, Rugo H, Chui S and Winer E: A phase III randomized trial of atezolizumab in combination with nab-paclitaxel as first line therapy for patients with metastatic triple-negative breast cancer. Cancer Res 76(Suppl 4): OT1-01-06, 2016.
100. Binder DC, Fu Y-X and Weichselbaum RR: Radiotherapy and immune checkpoint blockade: potential interactions and future directions. Trends Mol Med 21: 463-465, 2015.
101. Seyedin SN, Tang C and Welsh JW: Author's view: radiation and immunotherapy as systemic therapy for solid tumors. OncoImmunol 4: e986402, 2015.
102. Tang C, Wang X, Soh H, Seyedin S, Cortez MA, Krishnan S, Massarelli E, Hong D, Naing A, Diab A, Gomez D, Ye H, Heymach J, Komaki R, Allison JP, Sharma P and Welsh JW: Combining radiation and immunotherapy: A new systemic therapy for solid tumors? Cancer Immunol Res 2: 831-838, 2014.
103. Formenti SC and Demaria S: Combining radiotherapy and cancer immunotherapy: a paradigm shift. J Natl Cancer Inst 105: 256-265, 2013.
104. Parmiani G, Maccalli C and Maio M: Integrating immune checkpoint blockade with anti-neo/mutated antigens reactivity to increase the clinical outcome of immunotherapy. Vaccines 3: 420-428, 2015.
105. Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbé C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A and Urba WJ: Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363: 711-723, 2010.
106. Koyama S, Akbay EA, Li YY, Herter-Sprie GS, Buczkowski KA, Richards WG, Gandhi L, Redig AJ, Rodig SJ, Asahina H, Jones RE, Kulkarni MM, Kuraguchi M, Palakurthi S, Fecci PE, Johnson BE, Janne PA, Engelman JA, Gangadharan SP, Costa DB, Freeman GJ, Bueno R, Hodi FS, Dranoff G, Wong K-K and Hammerman PS: Adaptive resistance to therapeutic PD-1 blockade is associated with up-regulation of alternative immune checkpoints. Nat Commun 7: 10501, 2016.
107. Curti BD, Kovacsovics-Bankowski M, Morris N, Walker E, Chisholm L, Floyd K, Walker J, Gonzalez I, Meeuwsen T, Fox BA, Moudgil T, Miller W, Haley D, Coffey T, Fisher B, Delanty-Miller L, Rymarchyk N, Kelly T, Crocenzi T, Bernstein E, Sanbom R, Urba WJ and Weinberg AD: OX40 Ia a potent immune-stimulating target in late-stage cancer patients. Cancer Res 73: 7189-7198, 2013.
108. + T cells. Cancer Res 72: 6130-6141, 2012.
109. Voutsadakis IA: The network of pluripotency, epithelial mesenchymal transition and prognosis of breast cancer. Breast Cancer: Targets Ther 7: 303-319, 2015.
110. low breast cancer stem cells. Cancer Res 69: 8058-8066, 2009.
111. Santisteban M, Reiman JM, Asiedu MK, Behrens MD, Nassar A, Kalli KR, Haluska P, Ingle JN, Hartmann LC, Manjili MH, Radisky DC, Ferrone S and Knutson KL: Immune-induced Epithelial to Mesenchymal Transition in vivo generates breast cancer stem cells. Cancer Res 69: 2887-2895, 2009.
112. Noh KH, Lee Y-H, Jeon J-H, Kang TH, Mao C-P, Wu T-C and Kim TW: Cancer vaccination drives Nanog-dependent evolution of tumor cells toward an immune-resistant and stemlike phenotype. Cancer Res 72: 1717-1727, 2012.
113. Di Tomaso T, Mazzoleni S, Wang E, Sovena G, Clavenna D, Franzin A, Mortini P, Ferrone S, Doglioni C, Marincola FM, Galli R, Parmiani G and Maccalli C: Immunobiological characterization of cancer stem cells isolated from glioblastoma patients. Clin Cancer Res 16: 800-813, 2010.
114. Ma W, Gilligan BM, Yuan J and Li T: Current status and perspectives in translational biomarker research for PD-1/PD-L1 immune checkpoint blockade therapy. J Hematol Oncol 9: 47, 2016.