Thomas Gevaert

KU Leuven

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Roland de Wind

Université Libre de Bruxelles

Tomohagu Sugie

Kansai Medical University

Cécile Colpaert

AZ Turnhout

Stuart J. Schnitt

Brigham and Women's Hospital

Brad H. Nelson

BC Cancer Agency

Michael Christie

Walter and Eliza Hall Institute of Medical Research

Stephen M. Hewitt

National Cancer Institute

Hugo M. Horlings

Oncode Institute

Roberto Salgado

GZA Ziekenhuizen Campus Sint-Augustinus

Joseph A. Sparano

Icahn School of Medicine at Mount Sinai

Cooperative Institutions

Memorial Sloan Kettering Cancer Center

Dana-Farber Cancer Institute

Peter MacCallum Cancer Centre

Institut Jules Bordet

Brigham and Women's Hospital

Harvard University

The University of Texas MD Anderson Cancer Center

Massachusetts General Hospital

University of Melbourne

Institute of Cancer Research

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Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group

npj Breast Cancer (2020)

Mohamed Amgad Elisabeth Specht Stovgaard Eva Balslev Jeppe Thagaard Weijie Chen

Abstract Assessment of tumor-infiltrating lymphocytes (TILs) is increasingly recognized as an integral part of the prognostic workflow in triple-negative (TNBC) and HER2-positive breast cancer, as well as many other solid tumors. This recognition has come about thanks to standardized visual reporting guidelines, which helped to reduce inter-reader variability. Now, there are ripe opportunities to employ computational methods that extract spatio-morphologic predictive features, enabling computer-aided diagnostics. We detail the benefits of computational TILs assessment, the readiness of TILs scoring for computational assessment, and outline considerations for overcoming key barriers to clinical translation in this arena. Specifically, we discuss: 1. ensuring computational workflows closely capture visual guidelines and standards; 2. challenges and thoughts standards for assessment of algorithms including training, preanalytical, analytical, and clinical validation; 3. perspectives on how to realize the potential of machine learning models and to overcome the perceptual and practical limits of visual scoring.

10.1038/s41523-020-0154-2

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Citations (124)

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

npj Breast Cancer (2021)

Khalid El Bairi Harry R. Haynes Elizabeth F. Blackley Susan Fineberg Jeffrey Shear

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.

Tumor-infiltrating lymphocytes

Immune checkpoint

Clinical Oncology

Triple-negative breast cancer

10.1038/s41523-021-00346-1

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Citations (168)

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

PMC (2017)

Shona Hendry Roberto Salgado Thomas Gevaert Prudence A. Russell Thomas John

Solid tumor

Tumor-infiltrating lymphocytes

Source

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Citations (2)

Pitfalls in assessing stromal tumor infiltrating lymphocytes (sTILs) in breast cancer

npj Breast Cancer (2020)

Zuzana Kos Elvire Roblin Rim S. Kim Stefan Michiels Brandon D. Gallas

Abstract Stromal tumor-infiltrating lymphocytes (sTILs) are important prognostic and predictive biomarkers in triple-negative (TNBC) and HER2-positive breast cancer. Incorporating sTILs into clinical practice necessitates reproducible assessment. Previously developed standardized scoring guidelines have been widely embraced by the clinical and research communities. We evaluated sources of variability in sTIL assessment by pathologists in three previous sTIL ring studies. We identify common challenges and evaluate impact of discrepancies on outcome estimates in early TNBC using a newly-developed prognostic tool. Discordant sTIL assessment is driven by heterogeneity in lymphocyte distribution. Additional factors include: technical slide-related issues; scoring outside the tumor boundary; tumors with minimal assessable stroma; including lymphocytes associated with other structures; and including other inflammatory cells. Small variations in sTIL assessment modestly alter risk estimation in early TNBC but have the potential to affect treatment selection if cutpoints are employed. Scoring and averaging multiple areas, as well as use of reference images, improve consistency of sTIL evaluation. Moreover, to assist in avoiding the pitfalls identified in this analysis, we developed an educational resource available at www.tilsinbreastcancer.org/pitfalls .

Breast tumor

Tumor-infiltrating lymphocytes

10.1038/s41523-020-0156-0

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Citations (145)

Primary and Solitary Intradural Extramedullary Lesion: A Diagnostic Challenge

World Neurosurgery (2013)

P. Op de Beek C. Smets G. De Temmerman Thomas Gevaert Raf Sciot

Solitary Fibrous Tumor

Hemangiopericytoma

CD99

10.1016/j.wneu.2013.07.059

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Citations (0)

ASSESSMENT OF THE TREATMENT OF BREAST CARCINOMA WITH TOMOTHERAPY

Radiotherapy and Oncology (2009)

Truus Reynders Koen Tournel S. Heymann Vincent Vinh‐Hung Hilde Van Parijs

Tomotherapy

Breast carcinoma

10.1016/s0167-8140(12)73150-x

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Citations (0)

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 1: Assessing the host immune response, TILs in invasive breast carcinoma and ductal carcinoma in situ, metastatic tumor deposits and areas for further research

PMC (2017)

Shona Hendry Roberto Salgado Thomas Gevaert Prudence A. Russell Thomas John

Solid tumor

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Citations (0)

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

Advances in Anatomic Pathology (2017)

Shona Hendry Roberto Salgado Thomas Gevaert Prudence A. Russell Thomas John

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.

Tumor-infiltrating lymphocytes

10.1097/pap.0000000000000162

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Citations (578)

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

Advances in Anatomic Pathology (2017)

Shona Hendry Roberto Salgado Thomas Gevaert Prudence A. Russell Thomas John

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.

Tumor-infiltrating lymphocytes

10.1097/pap.0000000000000161

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Citations (652)

Status of Programmed Death Ligand 1 (PD-L1) by Immunohistochemistry and Scoring Algorithms

Current Drug Targets (2020)

Francesca Giunchi Thomas Gevaert Marina Scarpelli Michelangelo Fiorentino

The detection of the Programmed Death Ligand 1 (PD-L1) protein by immunohistochemistry is currently the only approved test predictive of response to drugs targeting the PD1/PDL1 axis. The role of this test is debated since several reagents have been used as companion diagnostics for different drugs on diverse immunostaining platforms. In addition, different scoring systems for PD-L1 immunohistochemistry have been applied in the registration studies regarding single drugs. This review deals with the various issues that are related to the immunohistochemical test for PD-L1. We discuss currently unsolved problems such as the advantages and the flaws of PD-L1 immunohistochemistry; the choice of the best reagents and the best scoring system. Finally, we review the current experiences on the role of immunohistochemistry for PD-L1 in clinical trials with immune checkpoint inhibitors.

Immunostaining

10.2174/1389450121666200123124642

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Citations (12)