Are tumor-infiltrating lymphocytes protagonists or background actors in patient selection for cancer immunotherapy?

References

• Li H, Fan X, Houghton J. Tumor microenvironment: the role of the tumor stroma in cancer. J Cell Biochem. 2007;101:805–815.
   PubMed Web of Science ®Google Scholar
• Galon J, Angell HK, Bedognetti D, et al. The continuum of cancer immunosurveillance: prognostic, predictive, and mechanistic signatures. Immunity. 2013;39:11–26.
   PubMed Web of Science ®Google Scholar
• Schreiber RD, Old LJ, Smyth MJ. Cancer immunoediting: integrating immunity’s roles in cancer suppression and promotion. Science. 2001;331:1565–1570.
   Web of Science ®Google Scholar
• Virchow R. Cellular pathology, Chance, F. Philadelphia: J.B. Lippincott; 1863. p. 219.
   Google Scholar
• Clark WH Jr, From L, Bernardino EA, et al. The histogenesis and biologic behavior of primary human malignant melanomas of the skin. Cancer Res. 1969;29:705–727.
   PubMed Web of Science ®Google Scholar
• Spiess PJ, Yang JC, Rosenberg SA. In vivo antitumor activity of tumor-infiltrating lymphocytes expanded in recombinant interleukin-2. J. Natl Cancer Inst. 1987;79:1067–1075.
   PubMed Web of Science ®Google Scholar
• Zhang L, Conejo-Garcia JR, Katsaros D, et al. Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. N Engl J Med. 2003;348:203–213.
   PubMed Web of Science ®Google Scholar
• Fridman WH, Galon J, Pagès F, et al. Prognostic and predictive impact of intra- and peritumoral immune infiltrates. Cancer Res. 2011;71:5601–5605.
   PubMed Web of Science ®Google Scholar
• Weiss SA, Han SW, Lui K, et al. Immunologic heterogeneity of tumor-infiltrating lymphocyte composition in primary melanoma. Hum Pathol. 2016;57:116–125.
   PubMed Web of Science ®Google Scholar
• Galon J, Bernhard M, Florence M, et al. Validation of the immunoscore (IM) as a prognostic marker in stage I/II/III colon cancer: results of a worldwide consortium-based analysis of 1,336 patients. J Clin Oncol. 2016;(suppl; abstr 3500).
   Google Scholar
• Krynitz B, Rozell BL, Lyth J, et al. Cutaneous malignant melanoma in the Swedish organ transplantation cohort: a study of clinicopathological characteristics and mortality. J Am Acad Dermatol. 2015;73:106–113.
   PubMed Web of Science ®Google Scholar
• Al-Shibli KI, Donnem T, Al-Saad S, et al. Prognostic effect of epithelial and stromal lymphocyte infiltration in non-small cell lung cancer. Clin Cancer Res. 2008;14:5220–5227.
   PubMed Web of Science ®Google Scholar
• Mahmoud SM, Paish EC, Powe DG, et al. Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer. J Clin Oncol. 2011;29:1949–1955.
   PubMed Web of Science ®Google Scholar
• Fukunaga A, Miyamoto M, Cho Y, et al. CD8+ tumor-infiltrating lymphocytes together with CD4+ tumor-infiltrating lymphocytes and dendritic cells improve the prognosis of patients with pancreatic adenocarcinoma. Pancreas. 2004;28:26–31.
   PubMed Web of Science ®Google Scholar
• Wolf GT, Chepeha DB, Bellile E, et al. Tumor infiltrating lymphocytes (TIL) and prognosis in oral cavity squamous carcinoma: a preliminary study. Oral Oncol. 2015;51:90–95.
   PubMed Web of Science ®Google Scholar
• Galon J, Mlecnik B, Bindea G, et al. Towards the introduction of the ‘immunoscore’ in the classification of malignant tumours. J Pathol. 2014;232:199–209.
   PubMed Web of Science ®Google Scholar
• Salgado R, Denkert C, Demaria S, et al. The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014. Ann Oncol. 2015;26:259–271.
   PubMed Web of Science ®Google Scholar
• Donnem T, Kilvaer TK, Andersen S, et al. Strategies for clinical implementation of TNM-immunoscore in resected nonsmall-cell lung cancer. Ann Oncol. 2016;27:225–232.
   PubMed Web of Science ®Google Scholar
• Morris M, Platell C, Iacopetta B. Tumor-infiltrating lymphocytes and perforation in colon cancer predict positive response to 5-fluorouracil chemotherapy. Clin Cancer Res. 2008;14:1413–1417.
   PubMed Web of Science ®Google Scholar
• Zingg U, Montani M, Frey DM, et al. Influence of neoadjuvant radio-chemotherapy on tumor infiltrating lymphocytes in squamous esophageal cancer. Eur J Surg Oncol. 2009;35:1268–1272.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Yasuda K, Nirei T, Sunami E, et al. Density of CD4(+) and CD8(+) T lymphocytes in biopsy samples can be a predictor of pathological response to chemoradiotherapy (CRT) for rectal cancer. Radiat Oncol. 2011;6:49.
   PubMed Web of Science ®Google Scholar
• West NR, Milne K, Truong PT, et al. Tumor-infiltrating lymphocytes predict response to anthracycline-based chemotherapy in estrogen receptor-negative breast cancer. Breast Cancer Res. 2011;13:R126.
   PubMed Web of Science ®Google Scholar
• Liu H, Zhang T, Ye J, et al. Tumor-infiltrating lymphocytes predict response to chemotherapy in patients with advance non-small cell lung cancer. Cancer Immunol Immunother. 2012;61:1849–1856.
   PubMed Web of Science ®Google Scholar
• Hodi FS, O’Day SJ, McDermott DF, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363:711–723.
   PubMed Web of Science ®Google Scholar
• Topalian SL, Hodi FS, Brahmer JR, et al. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012;366:2443–2454.
   PubMed Web of Science ®Google Scholar
• Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515:563–567.
   PubMed Web of Science ®Google Scholar
• Powles T, Eder JP, Fine GD, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature. 2014;515:558–562.
   PubMed Web of Science ®Google Scholar
• Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. N Engl J Med. 2015;372:311–319.
   PubMed Web of Science ®Google Scholar
• Korman AJ, Peggs KS, Allison JP. Checkpoint blockade in cancer immunotherapy. Adv Immunol. 2006;90:297–339.
   PubMed Web of Science ®Google Scholar
• Sanmamed MF, Chen L. Inducible expression of B7-H1 (PDL1) and its selective role in tumor site immune modulation. Cancer J. 2014;20:256–261.
   PubMed Web of Science ®Google Scholar
• Gentzler R, Hall R, Kunk PR, et al. Beyond melanoma: inhibiting the PD-1/PD-L1 pathway in solid tumors. Immunotherapy. 2016;8:583–600.
   PubMed Web of Science ®Google Scholar
• Motzer RJ, Escudier B, McDermott DF, et al. Nivolumab versus everolimus in advanced renal-cell carcinoma. N. Engl J Med. 2015;373:1803–1813.
   PubMed Web of Science ®Google Scholar
• Hammers HJ, Plimack ER, Infante JR et al. Phase I study of nivolumab in combination with ipilimumab in metastatic renal cell carcinoma (mRCC). Presented at: American Society of Clinical Oncology (ASCO) Annual Meeting 2014. Chicago, IL, USA, 2014.
   Google Scholar
• Chow LQ, Burtness B, Weiss J et al. A Phase Ib study of pembrolizumab in patients with human papilloma virus (HPV)-positive and negative head and neck cancer. Presented at: European Society for Medical Oncology (ESMO)2014 Congress. Madrid, 2014.
   Google Scholar
• Ott PA, Piha-Paul SA, Munster P et al. Pembrolizumab (MK-3475) for PD-L1-positive squamous cell carcinoma (SCC) of the anal canal: preliminary safety and efficacy results from KEYNOTE-028. Presented at: the European Cancer Congress (ECC 2015). Vienna, Austria, 2015.
   Google Scholar
• Segal NH, Antonia SJ, Brahmer JR et al. Preliminary data from a multi-arm expansion study of MEDI4736, an anti-PD-L1 antibody. Presented at: American Society of Clinical Oncology (ASCO) Annual Meeting 2014. Chicago, IL, USA, 2014.
   Google Scholar
• El-Khoueiry ABMI, Crocenzi TS, Hobart WT et al. Phase I/II safety and antitumor activity of nivolumab in patients with advanced hepatocellular carcinoma (HCC): CA209–040. Presented at: ASCO Annual Meeting 2015. Chicago, IL, USA, 2015.
   Google Scholar
• Muro K, Bang Y-J, Shankaran V et al. Relationship between PD-L1 expression and clinical outcomes in patients (Pts) with advanced gastric cancer treated with the anti-PD-1 monoclonal antibody pembrolizumab (Pembro; MK-3475) in KEYNOTE-012. Presented at: 2015 Gastrointestinal Cancers Symposium (ASCO GI). San Francisco, CA, 2015.
   Google Scholar
• Emens LAB, Cassier FS, De Lord P et al. Inhibition of PD-L1 by MPDL3280A leads to clinical activity in patients with metastatic triple-negative breast cancer. Presented at: Thirty-Seventh Annual CTRC-AACRSan Antonio Breast Cancer Symposium. San Antonio, TX, 2014.
   Google Scholar
• Teng MW, Ngiow SF, Ribas A, et al. Classifying cancers based on T-cell infiltration and PD-L1. Cancer Res. 2015;75:2139–2145.
   PubMed Web of Science ®Google Scholar
• Mei Z, Liu Y, Liu C, et al. Tumour-infiltrating inflammation and prognosis in colorectal cancer: systematic review and meta-analysis. Br J Cancer. 2014;110:1595–1605.
   PubMed Web of Science ®Google Scholar
• Geng Y, Shao Y, He W, et al. Prognostic role of tumor-infiltrating lymphocytes in lung cancer: a meta- analysis. Cell Physiol Biochem. 2015;37:1560–1571.
   PubMed Web of Science ®Google Scholar
• Hwang WT, Adams SF, Tahirovic E, et al. Prognostic significance of tumor-infiltrating T-cells in ovarian cancer: a meta-analysis. Gynecol Oncol. 2012;124:192–198.
   PubMed Web of Science ®Google Scholar
• Jiang D, Gao Z, Cai Z, et al. Clinicopathological and prognostic significance of FOXP3+ tumor infiltrating lymphocytes in patients with breast cancer: a meta-analysis. BMC Cancer. 2015;15:727.
   PubMed Web of Science ®Google Scholar
• Azimi F, Scolyer RA, Rumcheva P, et al. Tumor-infiltrating lymphocyte grade is an independent predictor of sentinel lymph node status and survival in patients with cutaneous melanoma. J Clin Oncol. 2012;30:2678–2683.
   PubMed Web of Science ®Google Scholar
• Rusakiewicz S, Semeraro M, Sarabi M, et al. Immune infiltrates are prognostic factors in localized gastrointestinal stromal tumors. Cancer Res. 2013;73:3499–3510.
   PubMed Web of Science ®Google Scholar
• Nakano O, Sato M, Naito Y, et al. Proliferative activity of intratumoral CD8þ T-lymphocytes as a prognostic factor in human renal cell carcinoma clinicopathologic demonstration of antitumor immunity. Cancer Res. 2001;61:5132–5136.
   PubMed Web of Science ®Google Scholar
• Ward MJ, Thirdborough SM, Mellows T, et al. Tumour-infiltrating lymphocytes predict for outcome in HPV-positive oropharyngeal cancer. Br J Cancer. 2014;110:489–500.
   PubMed Web of Science ®Google Scholar
• Wansom D, Light E, Thomas D, et al. Infiltrating lymphocytes and human papillomavirus-16-associated oropharyngeal cancer. Laryngoscope. 2012;122:121–127.
   PubMed Web of Science ®Google Scholar
• Badoual C, Hans S, Rodriguez J, et al. Prognostic value of tumor-infiltrating CD4+ T-cell subpopulations in head and neck cancers. Clin Cancer Res. 2006;12:465–472.
   PubMed Web of Science ®Google Scholar
• Berghuis D, Santos SJ, Baelde HJ, et al. Pro-inflammatory chemokine-chemokine receptor interactions within the Ewing sarcoma microenvironment determine CD8(+) T-lymphocyte infiltration and affect tumour progression. J Pathol. 2011;223:347–357.
   PubMed Web of Science ®Google Scholar
• Jass JR. Lymphocytic infiltration and survival in rectal cancer. J Clin Pathol. 1986;39:585–589.
   PubMed Web of Science ®Google Scholar
• Clark WH Jr, Elder DE, Guerry D, et al. Model predicting survival in stage I melanoma based on tumor progression. J Natl Cancer Inst. 1989;81:1893–1904.
   PubMed Web of Science ®Google Scholar
• van Houdt IS, Sluijter BJ, Moesbergen LM, et al. Favorable outcome in clinically stage II melanoma patients is associated with the presence of activated tumor infiltrating T-lymphocytes and preserved MHC class I antigen expression. Int J Cancer. 2008;123:609–615.
   PubMed Web of Science ®Google Scholar
• Burton AL, Roach BA, Mays MP, et al. Prognostic significance of tumor infiltrating lymphocytes in melanoma. Am Surg. 2011;77:188–192.
   PubMed Web of Science ®Google Scholar
• Lee N, Zakka LR, Mihm MC Jr, et al. Tumour-infiltrating lymphocytes in melanoma prognosis and cancer immunotherapy. Pathology. 2016;48:177–187.
   PubMed Web of Science ®Google Scholar
• Mihm MC Jr, Clemente CG, Cascinelli N. Tumor infiltrating lymphocytes in lymph node melanoma metastases: a histopathologic prognostic indicator and an expression of local immune response. Lab Invest. 1996;74:43–47.
   PubMed Web of Science ®Google Scholar
• Cochran AJ, Morton DL, Stern S, et al. Sentinel lymph nodes show profound downregulation of antigen-presenting cells of the paracortex: implications for tumor biology and treatment. Mod Pathol. 2001;14:604–608.
   PubMed Web of Science ®Google Scholar
• Cochran AJ, Wen DR, Huang RR, et al. Prediction of metastatic melanoma in nonsentinel nodes and clinical outcome based on the primary melanoma and the sentinel node. Mod Pathol. 2004;17:747–755.
   PubMed Web of Science ®Google Scholar
• Mohos A, Sebestyén T, Liszkay G, et al. Immune cell profile of sentinel lymph nodes in patients with malignant melanoma-FOXP3+ cell density in cases with positive sentinel node status is associated with unfavorable clinical outcome. J Transl Med. 2013;18:11–43.
   Google Scholar
• Goc J, Germain C, Vo-Bourgais TK, et al. Dendritic cells in tumor-associated tertiary lymphoid structures signal a Th1 cytotoxic immune contexture and license the positive prognostic value of infiltrating CD8+ T cells. Cancer Res. 2014;74:705–715.
   PubMed Web of Science ®Google Scholar
• Kayser G, Schulte-Uentrop L, Sienel W, et al. Stromal CD4/CD25 positive T-cells are a strong and independent prognostic factor in non-small cell lung cancer patients, especially with adenocarcinomas. Lung Cancer. 2012;76:445–451.
   PubMed Web of Science ®Google Scholar
• Adams S, Gray RJ, Demaria S, et al. Prognostic value of tumor-infiltrating lymphocytes in triple negative breast cancers from two phase III randomized adjuvant breast cancer trials: ECOG 2197 and ECOG 1199. J Clin Oncol. 2014;32:2959–2967.
   PubMed Web of Science ®Google Scholar
• Duchnowska R, Pęksa R, Radecka B, et al. Immune response in breast cancer brain metastases and their microenvironment: the role of the PD-1/PD-L axis. Breast Cancer Res. 2016;18:43.
   PubMed Web of Science ®Google Scholar
• Adams SF, Levine DA, Cadungog MG, et al. Intraepithelial T cells and tumor proliferation: impact on the benefit from surgical cytoreduction in advanced serous ovarian cancer. Cancer. 2009;115:2891–2902.
   PubMed Web of Science ®Google Scholar
• Zitvogel L, Apetoh L, Ghiringhelli F, et al. Immunological aspects of cancer chemotherapy. Nat Rev Immunol. 2008;8:59–73.
   PubMed Web of Science ®Google Scholar
• Ladoire S, Mignot G, Dabakuyo S, et al. In situ immune response after neoadjuvant chemotherapy for breast cancer predicts survival. J Pathol. 2011;224:389–400.
   PubMed Web of Science ®Google Scholar
• Formenti SC, Demaria S. Systemic effects of local radiotherapy. Lancet Oncol. 2009;10:718–726.
   PubMed Web of Science ®Google Scholar
• Kitayama J, Yasuda K, Kawai K, et al. Circulating lymphocyte number has a positive association with tumor response in neoadjuvant chemoradiotherapy for advanced rectal cancer. Radiat Oncol. 2010;5:47.
   PubMed Web of Science ®Google Scholar
• Bösmüller H, Haitchi-Petnehazy S, Webersinke G, et al. Intratumoral lymphocyte density in serous ovarian carcinoma is superior to ERCC1 expression for predicting response to platinum-based therapy. Virchows Arch. 2011;459:183–191.
   PubMed Web of Science ®Google Scholar
• Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015;27:450–461.
   PubMed Web of Science ®Google Scholar
• Greenwald RJ, Freeman GJ, Sharpe AH. The B7 family revisited. Annu Rev Immunol. 2005;23:515–548.
   PubMed Web of Science ®Google Scholar
• Swaika A, Hammond WA, Joseph RW. Current state of anti-PD-L1 and anti-PD-1 agents in cancer therapy. Mol Immunol. 2015;67:4–17.
   PubMed Web of Science ®Google Scholar
• Shin DS, Ribas A. The evolution of checkpoint blockade as a cancer therapy: what’s here, what’s next? Curr Opin Immunol. 2015;33:23–35.
   PubMed Web of Science ®Google Scholar
• Wolchok JD, Kluger H, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma. N Engl J Med. 2013;369:122–133.
   PubMed Web of Science ®Google Scholar
• Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol. 2012;12(4):253–268.
   PubMed Web of Science ®Google Scholar
• Draghiciu O, Lubbers J, Nijman HW, et al. Myeloid derived suppressor cells – an overview of combat strategies to increase immunotherapy efficacy. Oncoimmunology. 2015;3:4.
   Google Scholar
• Platten M, Wick W, van den Eynde BJ. Tryptophan catabolism in cancer: beyond IDO and tryptophan depletion. Cancer Res. 2012;72:5435–5440.
   PubMed Web of Science ®Google Scholar
• Holmgaard RB, Zamarin D, Munn DH, et al. Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4. J Exp Med. 2013;210:1389–1402.
   PubMed Web of Science ®Google Scholar
• Wang W, Yu D, Sarnaik AA, et al. Biomarkers on melanoma patient T cells associated with ipilimumab treatment. J Transl Med. 2012;10:146.
   PubMed Web of Science ®Google Scholar
• Hamid O, Schmidt H, Nissan A, et al. A prospective phase II trial exploring the association between tumor microenvironment biomarkers and clinical activity of ipilimumab in advanced melanoma. J Transl Med. 2011;28:9–204.
   Google Scholar
• Tumeh PC, Harview CL, Yearley JH, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515:568–571.
   PubMed Web of Science ®Google Scholar
• Bald T, Landsberg J, Lopez-Ramos D, et al. Immune cell-poor melanomas benefit from PD-1 blockade after targeted type I IFN activation. Cancer Discov. 2014;4:674–687.
   PubMed Web of Science ®Google Scholar
• Taube JM, Klein A, Brahmer JR, 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;20:5064–5074.
   PubMed Web of Science ®Google Scholar
• Fehrenbacher L, Spira A, Ballinger M, et al. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet. 2016;387:1837–1846.
   PubMed Web of Science ®Google Scholar
• Grigg C, Rizvi NA. PD-L1 biomarker testing for non-small cell lung cancer: truth or fiction? J Immunother Cancer. 2016;4:48.
   PubMed Web of Science ®Google Scholar
• Brambilla E, Le Teuff G, Marguet S, et al. Prognostic effect of tumor lymphocytic infiltration in resectable non-small-cell lung cancer. J Clin Oncol. 2016;34:1223–1230.
   PubMed Web of Science ®Google Scholar
• Zou W, Wolchok JD, Chen L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers and combinations. Sci Transl Med. 2016;8:328rv4.
   PubMed Web of Science ®Google Scholar
• Spranger S, Bao R, Gajewski TF. Melanoma-intrinsic beta-catenin signaling prevents anti-tumour immunity. Nature. 2015;523:231–235.
   PubMed Web of Science ®Google Scholar
• Peng D, Kryczek I, Nagarsheth N, et al. Epigenetic silencing of TH1-type chemokines shapes tumour immunity and immunotherapy. Nature. 2015;527:249–253.
   PubMed Web of Science ®Google Scholar
• Huang MA, Krishnadas DK, Lucas KG. Cellular and antibody based approaches for pediatric cancer immunotherapy. J Immunol Res. 2015;2015:1–7.
   Web of Science ®Google Scholar
• Chowdhury F, Dunn S, Mitchell S, et al. PD-L1 and CD8(+)PD1(+) lymphocytes exist as targets in the pediatric tumor microenvironment for immunomodulatory therapy. Oncoimmunology. 2015;4:e1029701.
   Web of Science ®Google Scholar
• Routh JC, Ashley RA, Sebo TJ, et al. B7-H1 expression in Wilms tumor: correlation with tumor biology and disease recurrence. J Urol. 2008;179:1954–1960.
   PubMed Web of Science ®Google Scholar
• Uehara S, Nakahata K, Kawatsu M, et al. The PDL1 expression increases after consecutive multimodal therapies in neuroblastoma. Pediatr Blood Cancer. 2015;62:S334.
   Web of Science ®Google Scholar
• Aoki T, Hino M, Koh K, et al. Low frequency of programmed death ligand 1 expression in pediatric cancers. Pediatr Blood Cancer. 2016;63:1461–1464.
   PubMed Web of Science ®Google Scholar
• Herrera FG, Bourhis J, Coukos G. Radiotherapy combination opportunities leveraging immunity for the next oncology practice. CA Cancer J Clin. 2017;67:65–85.
   PubMed Web of Science ®Google Scholar
• Pilones KA, Vanpouille-Box C, Demaria S. Combination of radiotherapy and immune checkpoint inhibitors. Semin Radiat Oncol. 2015;25:28–33.
   PubMed Web of Science ®Google Scholar
• Ribeiro Gomes J, Schmerling RA, Haddad CK, et al. Analysis of the abscopal effect with anti-PD1 therapy in patients with metastatic solid tumors. J Immunother. 2016;39:367–372.
   PubMed Web of Science ®Google Scholar
• Spira AI, Park K, Mazieres J, et al. Efficacy, safety and predictive biomarker results from a randomized phase II study comparing MPDL3280A vs docetaxel in 2L/3L NSCLC (POPLAR) [abstract]. J Clinoncol. 2015;33(suppl):8010.
   Google Scholar
• Kerr KM, Hirsch FR. Programmed death ligand-1 immunohistochemistry: friend or foe? Arch Pathol Lab Med. 2016;140:326–331.
   PubMed Web of Science ®Google Scholar
• Feng Z, Puri S, Moudgil T, et al. Multispectral imaging of formalin-fixed tissue predicts ability to generate tumor infiltrating lymphocytes from melanoma. J Immunother Cancer. 2015;3:47.
   PubMed Web of Science ®Google Scholar