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Adv Anat Pathol. 2017 Nov;24(6):311-335. doi: 10.1097/PAP.0000000000000161.

Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non-Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors.

Author information

1
Departments of *Pathology §§§Medical Oncology, Peter MacCallum Cancer Centre, Melbourne †The Sir Peter MacCallum Department of Oncology Departments of **Pathology ∥∥Medicine, University of Melbourne ¶¶Department of Anatomical Pathology, Royal Melbourne Hospital, Parkville #Department of Anatomical Pathology, St Vincent's Hospital Melbourne, Fitzroy ††Department of Medical Oncology, Austin Health ‡‡Olivia Newton-John Cancer Research Institute, Heidelberg §§School of Cancer Medicine, La Trobe University, Bundoora §§§§§Centre for Clinical Research and School of Medicine, The University of Queensland ∥∥∥∥∥Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane §§§§§§§§§§The Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst ∥∥∥∥∥∥∥∥∥∥Australian Clinical Labs, Bella Vista ‡‡‡‡‡‡‡‡‡‡‡‡Directorate of Surgical Pathology, SA Pathology §§§§§§§§§§§§Discipline of Medicine, Adelaide University, Adelaide, Australia ***********Department of Surgical Oncology, Netherlands Cancer Institute †††††††††††††Department of Pathology ##Divisions of Diagnostic Oncology & Molecular Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, The Netherlands ###Université Paris-Est ****INSERM, UMR 955 ††††Département de pathologie, APHP, Hôpital Henri-Mondor, Créteil ∥∥∥∥∥∥∥∥∥Service de Biostatistique et d'Epidémiologie, Gustave Roussy, CESP, Inserm U1018, Université-Paris Sud, Université Paris-Saclay ¶¶¶¶¶¶¶¶¶¶INSERM Unit U981, and Department of Medical Oncology, Gustave Roussy, Villejuif ##########Faculté de Médecine, Université Paris Sud, Kremlin-Bicêtre †††††††Department of Surgical Pathology and Biopathology, Jean Perrin Comprehensive Cancer Centre ‡‡‡‡‡‡‡University of Auvergne UMR1240, Clermont-Ferrand, France ‡‡‡‡Department of Medicine, Clinical Division of Oncology §§§§Institute of Neurology, Comprehensive Cancer Centre Vienna, Medical University of Vienna, Vienna ††††††††††††††Institute of Pathology, Medical University of Graz, Austria ∥∥∥∥European Institute of Oncology ¶¶¶¶School of Medicine ######Department of Pathology, Istituto Europeo di Oncologia, University of Milan, Milan ¶¶¶¶¶¶¶¶¶¶¶¶¶Department of Surgery, Oncology and Gastroenterology, University of Padova #############Medical Oncology 2, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy †††††Molecular Oncology Group, Vall d'Hebron Institute of Oncology, Barcelona †††††††††††Pathology Department, IIS-Fundacion Jimenez Diaz, UAM, Madrid, Spain §Department of Pathology and TCRU, GZA ¶¶¶Department of Pathology, GZA Ziekenhuizen, Antwerp ∥Laboratory of Experimental Urology, Department of Development and Regeneration, KU Leuven ‡‡‡‡‡‡‡‡‡‡‡Department of Pathology, University Hospital Leuven, Leuven, Belgium ¶Department of Pathology, AZ Klina, Brasschaat ††††††Department of Pathology, GZA Ziekenhuizen, Sint-Augustinus, Wilrijk ∥∥∥Molecular Immunology Unit ‡‡‡‡‡‡Department of Medical Oncology, Institut Jules Bordet, Université Libre de Bruxelles ‡Breast Cancer Translational Research Laboratory/Breast International Group, Institut Jules Bordet **************European Organisation for Research and Treatment of Cancer (EORTC) Headquarters *******Department of Pathology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium §§§§§§§Department of Surgery, Kansai Medical School, Hirakata, Japan #######Severance Biomedical Science Institute and Department of Medical Oncology, Yonsei University College of Medicine, Seoul, South Korea ∥∥∥∥∥∥∥∥Tumor Pathology Department, Maria Sklodowska-Curie Memorial Cancer Center ¶¶¶¶¶¶¶¶Institute of Oncology, Gliwice Branch, Gliwice, Poland ‡‡‡‡‡‡‡‡‡‡‡‡‡‡Pathology and Tissue Analytics, Roche Innovation Centre Munich, Penzberg †††††††††Institute of Pathology, Charité Universitätsmedizin Berlin ‡‡‡‡‡‡‡‡‡VMscope GmbH, Berlin ¶¶¶¶¶¶¶¶¶German Breast Group GmbH, Neu-Isenburg, Germany **********Trev & Joyce Deeley Research Centre, British Columbia Cancer Agency ††††††††††Department of Biochemistry and Microbiology, University of Victoria, Victoria Departments of ‡‡‡‡‡‡‡‡‡‡Medical Genetics #########Pathology and Laboratory Medicine ¶¶¶¶¶¶¶¶¶¶¶Department of Pathology and Laboratory Medicine, Genetic Pathology Evaluation Centre, University of British Columbia, Vancouver, BC ###########Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Canada §§§§§§§§§§§Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, Doha, Qatar ‡‡‡‡‡‡‡‡Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center §§§§§§§§Warren Alpert Medical School of Brown University, Providence ¶¶¶¶¶National Surgical Adjuvant Breast and Bowel Project Operations Center/NRG Oncology, Pittsburgh, PA †††Breast Cancer Research Program, Vanderbilt Ingram Cancer Center, Vanderbilt University Departments of ‡‡‡Pathology, Microbiology and Immunology ########Department of Medicine, Vanderbilt University Medical Centre *********Vanderbilt Ingram Cancer Center, Nashville §§§§§§§§§Department of Pathology, Yale University School of Medicine, New Haven ∥∥∥∥∥∥∥∥∥∥∥Department of Oncology, Montefiore Medical Centre, Albert Einstein College of Medicine ∥∥∥∥∥∥∥Montefiore Medical Center ¶¶¶¶¶¶¶The Albert Einstein College of Medicine, Bronx, NY ********Department of Pathology, Brigham and Women's Hospital #####Cancer Research Institute and Department of Pathology, Beth Israel Deaconess Cancer Center ******Harvard Medical School ¶¶¶¶¶¶¶¶¶¶¶¶Division of Hematology-Oncology, Beth Israel Deaconess Medical Center ††††††††Department of Cancer Biology ‡‡‡‡‡‡‡‡‡‡‡‡‡Dana-Farber Cancer Institute, Boston, MA ∥∥∥∥∥∥∥∥∥∥∥∥∥Department of Medicine, Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO ‡‡‡‡‡Department of Cancer Biology, Mayo Clinic, Jacksonville, FL ∥∥∥∥∥∥Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN ¶¶¶¶¶¶Cancer Immunotherapy Trials Network, Central Laboratory and Program in Immunology, Fred Hutchinson Cancer Research Center, Seattle, WA ††††††††††††Department of Pathology, New York University Langone Medical Centre ############New York University Medical School *************Perlmutter Cancer Center §§§§§§§§§§§§§Pulmonary Pathology, New York University Center for Biospecimen Research and Development, New York University ***************Department of Pathology, Memorial Sloan-Kettering Cancer Center ####Departments of Radiation Oncology and Pathology, Weill Cornell Medicine, New York, NY *****Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX ∥∥∥∥∥∥∥∥∥∥∥∥Pathology Department, Stanford University Medical Centre, Stanford ∥∥∥∥∥∥∥∥∥∥∥∥∥∥Department of Pathology, Stanford University, Palo Alto ***Department of Pathology, School of Medicine, University of California, San Diego §§§§§§§§§§§§§§Research Pathology, Genentech Inc., South San Francisco, CA *************Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda ¶¶¶¶¶¶¶¶¶¶¶¶¶¶Translational Sciences, MedImmune, Gaithersberg, MD §§§§§§Academic Medical Innovation, Novartis Pharmaceuticals Corporation, East Hanover ##############Translational Medicine, Merck & Co. Inc., Kenilworth, NJ.

Abstract

Assessment of the immune response to tumors is growing in importance as the prognostic implications of this response are increasingly recognized, and as immunotherapies are evaluated and implemented in different tumor types. However, many different approaches can be used to assess and describe the immune response, which limits efforts at implementation as a routine clinical biomarker. In part 1 of this review, we have proposed a standardized methodology to assess tumor-infiltrating lymphocytes (TILs) in solid tumors, based on the International Immuno-Oncology Biomarkers Working Group guidelines for invasive breast carcinoma. In part 2 of this review, we discuss the available evidence for the prognostic and predictive value of TILs in common solid tumors, including carcinomas of the lung, gastrointestinal tract, genitourinary system, gynecologic system, and head and neck, as well as primary brain tumors, mesothelioma and melanoma. The particularities and different emphases in TIL assessment in different tumor types are discussed. The standardized methodology we propose can be adapted to different tumor types and may be used as a standard against which other approaches can be compared. Standardization of TIL assessment will help clinicians, researchers and pathologists to conclusively evaluate the utility of this simple biomarker in the current era of immunotherapy.

PMID:
28777143
PMCID:
PMC5638696
DOI:
10.1097/PAP.0000000000000161
[Indexed for MEDLINE]
Free PMC Article

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