Assessing Tumor-infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method From the International Immunooncology Biomarkers Working Group: Part 1: Assessing the Host Immune Response, TILs in Invasive Breast Carcinoma and Ductal Carcinoma In Situ, Metastatic Tumor Deposits and Areas for Further Research
Authors: Hendry Shona , Salgado Roberto , Gevaert Thomas , Russell Prudence A. , John Tom , Thapa Bibhusal , Christie Michael , van de Vijver Koen , Estrada M.V. , Gonzalez-Ericsson Paula I. , Sanders Melinda , Solomon Benjamin , Solinas Cinzia , Van den Eynden Gert G.G.M. , Allory Yves , Preusser Matthias , Hainfellner Johannes , Pruneri Giancarlo , Vingiani Andrea , Demaria Sandra , Symmans Fraser , Nuciforo Paolo , Comerma Laura , Thompson E.A. , Lakhani Sunil , Kim Seong-Rim , Schnitt Stuart , Colpaert Cecile , Sotiriou Christos , Scherer Stefan J. , Ignatiadis Michail , Badve Sunil , Pierce Robert H. , Viale Giuseppe , Sirtaine Nicolas , Penault-Llorca Frederique , Sugie Tomohagu , Fineberg Susan , Paik Soonmyung , Srinivasan Ashok , Richardson Andrea , Wang Yihong , Chmielik Ewa , Brock Jane , Johnson Douglas B. , Balko Justin , Wienert Stephan , Bossuyt Veerle , Michiels Stefan , Ternes Nils , Burchardi Nicole , Luen Stephen J. , Savas Peter , Klauschen Frederick , Watson Peter H. , Nelson Brad H. , Criscitiello Carmen , O’Toole Sandra , Larsimont Denis , de Wind Roland , Curigliano Giuseppe , André Fabrice , Lacroix-Triki Magali , van de Vijver Mark , Rojo Federico , Floris Giuseppe , Bedri Shahinaz , Sparano Joseph , Rimm David , Nielsen Torsten , Kos Zuzana , Hewitt Stephen , Singh Baljit , Farshid Gelareh , Loibl Sibylle , Allison Kimberly H. , Tung Nadine , Adams Sylvia , Willard-Gallo Karen , Horlings Hugo M. , Gandhi Leena , Moreira Andre , Hirsch Fred , Dieci Maria V. , Urbanowicz Maria , Brcic Iva , Korski Konstanty , Gaire Fabien , Koeppen Hartmut , Lo Amy , Giltnane Jennifer , Rebelatto Marlon C. , Steele Keith E. , Zha Jiping , Emancipator Kenneth , Juco Jonathan W. , Denkert Carsten , Reis-Filho Jorge , Loi Sherene , Fox Stephen B. 
Published: August 2017

Assessment of tumor-infiltrating lymphocytes (TILs) in histopathologic specimens can provide important prognostic information in diverse solid tumor types, and may also be of value in predicting response to treatments. However, implementation as a routine clinical biomarker has not yet been achieved. As successful use of immune checkpoint inhibitors and other forms of immunotherapy become a clinical reality, the need for widely applicable, accessible, and reliable immunooncology biomarkers is clear. In part 1 of this review we briefly discuss the host immune response to tumors and different approaches to TIL assessment. We propose a standardized methodology to assess TILs in solid tumors on hematoxylin and eosin sections, in both primary and metastatic settings, based on the International Immuno-Oncology Biomarker Working Group guidelines for TIL assessment in invasive breast carcinoma. A review of the literature regarding the value of TIL assessment in different solid tumor types follows in part 2. The method we propose is reproducible, affordable, easily applied, and has demonstrated prognostic and predictive significance in invasive breast carcinoma. This standardized methodology may be used as a reference against which other methods are compared, and should be evaluated for clinical validity and utility. Standardization of TIL assessment will help to improve consistency and reproducibility in this field, enrich both the quality and quantity of comparable evidence, and help to thoroughly evaluate the utility of TILs assessment in this era of immunotherapy.