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Review
. 2021 Dec 1;7(1):150.
doi: 10.1038/s41523-021-00346-1.

The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group

Khalid El Bairi  1 , Harry R Haynes  2   3 , Elizabeth Blackley  4 , Susan Fineberg  5 , Jeffrey Shear  6 , Sophia Turner  7 , Juliana Ribeiro de Freitas  8 , Daniel Sur  9 , Luis Claudio Amendola  10 , Masoumeh Gharib  11 , Amine Kallala  12 , Indu Arun  13 , Farid Azmoudeh-Ardalan  14 , Luciana Fujimoto  15 , Luz F Sua  16 , Shi-Wei Liu  17 , Huang-Chun Lien  18 , Pawan Kirtani  19 , Marcelo Balancin  20 , Hicham El Attar  21 , Prerna Guleria  22 , Wenxian Yang  23 , Emad Shash  24 , I-Chun Chen  25   26 , Veronica Bautista  27 , Jose Fernando Do Prado Moura  28 , Bernardo L Rapoport  29   30 , Carlos Castaneda  31   32 , Eunice Spengler  33 , Gabriela Acosta-Haab  34 , Isabel Frahm  35 , Joselyn Sanchez  36 , Miluska Castillo  36 , Najat Bouchmaa  37 , Reena R Md Zin  38 , Ruohong Shui  39 , Timothy Onyuma  40 , Wentao Yang  39 , Zaheed Husain  41 , Karen Willard-Gallo  42 , An Coosemans  43 , Edith A Perez  44 , Elena Provenzano  45 , Paula Gonzalez Ericsson  46 , Eduardo Richardet  47 , Ravi Mehrotra  48 , Sandra Sarancone  49 , Anna Ehinger  50 , David L Rimm  51 , John M S Bartlett  52   53   54 , Giuseppe Viale  55 , Carsten Denkert  56 , Akira I Hida  57 , Christos Sotiriou  58 , Sibylle Loibl  59 , Stephen M Hewitt  60 , Sunil Badve  61 , William Fraser Symmans  62 , Rim S Kim  63 , Giancarlo Pruneri  64 , Shom Goel  4   65 , Prudence A Francis  65   66 , Gloria Inurrigarro  67 , Rin Yamaguchi  68 , Hernan Garcia-Rivello  69 , Hugo Horlings  70 , Said Afqir  71 , Roberto Salgado  4   72 , Sylvia Adams  73 , Marleen Kok  74 , Maria Vittoria Dieci  75   76 , Stefan Michiels  77 , Sandra Demaria  78 , Sherene Loi  4   65 ; International Immuno-Oncology Biomarker Working Group
Collaborators, Affiliations
Review

The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group

Khalid El Bairi et al. NPJ Breast Cancer. .

Abstract

The advent of immune-checkpoint inhibitors (ICI) in modern oncology has significantly improved survival in several cancer settings. A subgroup of women with breast cancer (BC) has immunogenic infiltration of lymphocytes with expression of programmed death-ligand 1 (PD-L1). These patients may potentially benefit from ICI targeting the programmed death 1 (PD-1)/PD-L1 signaling axis. The use of tumor-infiltrating lymphocytes (TILs) as predictive and prognostic biomarkers has been under intense examination. Emerging data suggest that TILs are associated with response to both cytotoxic treatments and immunotherapy, particularly for patients with triple-negative BC. In this review from The International Immuno-Oncology Biomarker Working Group, we discuss (a) the biological understanding of TILs, (b) their analytical and clinical validity and efforts toward the clinical utility in BC, and (c) the current status of PD-L1 and TIL testing across different continents, including experiences from low-to-middle-income countries, incorporating also the view of a patient advocate. This information will help set the stage for future approaches to optimize the understanding and clinical utilization of TIL analysis in patients with BC.

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Conflict of interest statement

S. Loi has received research funding to her institution from Novartis, Bristol Meyers Squibb, Merck, Roche-Genentech, Puma Biotechnology, Pfizer, Eli Lilly, Nektar Therapeutics AstraZeneca, and Seattle Genetics. S. Loi has acted as a consultant (not compensated) to Seattle Genetics, Pfizer, Novartis, BMS, Merck, AstraZeneca, and Roche-Genentech. S. Loi has acted as a consultant (paid to her institution) to Aduro Biotech, Novartis, GlaxoSmithKline, Roche-Genentech, Puma Biotechnology, AstraZeneca, and G1 Therapeutics. S. Loi is a Scientific Advisory Board Member of Akamara Therapeutics. S.D. has received research funding from institutions from Lytix Biopharma and Nanobiotix is a scientific advisory board member of Lytix Biopharma and has acted as an ad-hoc consultant (compensated) to Ono Pharma USA Inc, EMD Serono, and Mersana Therapeutics. S.G. is the recipient of lab research funding from Eli Lilly and Co and G1 Therapeutics. Shom Goel has served as a paid advisory board member for Eli Lilly and Co, G1 Therapeutics, Pfizer, and Novartis. S.G. also conducts clinical research sponsored by Eli Lilly and Co. S. Loibl reports grants and others from Abbvie, grants and other from Amgen, grants and other from Celgene, grants and other from Novartis, grants and other from Roche, other from Seattle Genetics, other from PriME/Medscape, personal fees from Chugai, grants and other from Daiichi-Sankyo, other from Lilly, other from Samsung, other from BMS, other from Puma, other from MSD, grants from Immunomedics, grants and other from AstraZeneca, grants and other from Pfizer, other from Pierre Fabre and other from Merck outside the submitted work; In addition, Dr. Loibl has a patent EP14153692.0 pending. J.M.S.B. BSc, PhD, FRCPath has consultancies for Insight Genetics, Inc. BioNTech AG Biotheranostics, Inc. Pfizer RNA Diagnostics Inc. oncoXchange/MedcomXchange Communications Inc. Herbert Smith French Solicitors OncoCyte Corporation SCIENTIFIC ADVISORY BOARD MedcomXchange Communications Inc. HONORARIA NanoString Technologies, Inc. Oncology Education Biotheranostics, Inc. MedcomXchange Communications Inc. RESEARCH FUNDING Thermo Fisher Scientific GenoptixAgendiaNanoString Technologies, Inc. Stratifyer GmbH Biotheranostics, Inc. TRAVEL, ACCOMMODATIONS, EXPENSES Biotheranostics, Inc. NanoString Technologies, Inc. Breast Cancer Society of Canada PATENTS—APPLIED Jan 2017: Methods and Devices for Predicting Anthracycline Treatment Efficacy, US utility—15/325,472; EPO—15822898.1; Canada—not yet assigned Jan 2017: Systems, Devices and Methods for Constructing and Using a Biomarker, US utility—15/328,108; EPO—15824751.0; Canada—not yet assigned Oct 2016: Histone gene module predicts anthracycline benefit, PCT/CA2016/000247 Dec 2016: 95-Gene Signature of Residual Risk Following Endocrine Treatment, PCT/CA2016/000304 Dec 2016: Immune Gene Signature Predicts Anthracycline Benefit, PCT/CA2016/000305 June 2020: Use of Molecular Classifiers to Diagnose, Treat and Prognose Prostate Cancer, US Provisional 63/040.692 INVENTION DISCLOSURE Disclosure Name: A Molecular Classifier for Personalized Risk Stratification for Patients with Prostate Cancer, Date: 21/08/2019. P.A.F. has received Honoraria from AstraZeneca and Novartis and Traveled to give overseas lectures from Ipsen. B.L.R. reports non-financial support from HalioDx, in the form of a collaborative association on a non-remunerative basis, during the conduct of the study. D.R. reports grants and personal fees from Amgen and AstraZeneca, Cepheid, Konica Minolta InVicro, NextCure, Ultivue, and Eli Lilly; personal fees from Bristol Myers Squibb, Cell Signaling Technology, Daiichi Sankyo, Danaher, GSK, Merck, Nanostring Technologies, Odonate, Paige. AI, Roche, Sanofi, and Ventana; grants from Navigate Biopharma; and personal royalties from RareCyte related to a patent on circulating cancer cells outside of the submitted work. A.E. is a Roche advisory board and Lecturer paid by Roche, Amgen, and Novartis. M.V.D. has personal fees for advisory/consultancy roles from Eli Lilly, Celgene, Novartis, and Genomic Health. R.Y. has received support from Chugai pharmaceutical company. S.M. has conflicts of interest not related to this study including statistical advice for IDDI and Janssen Cilag and is an Independent Data Monitoring Committee member for Hexal, Steba, IQVIA, Roche, Sensorion, Biophytis, Servier, and Yuan. M.K. Institution receives funding from BMS, Roche, AZ/Medimmune. M.K. has an advisory role for BMS, Roche, MSD, and Daiichi. R.S. reports non-financial support from Merck and Bristol Myers Squibb; research support from Merck, Puma Biotechnology, and Roche; and personal fees from Roche for an advisory board related to a trial-research project. The remaining authors declare no competing interests.

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