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

Khalid El Bairi; Harry R. Haynes; Elizabeth Blackley; Susan Fineberg; Jeffrey Shear; Sophia Turner; Juliana Ribeiro de Freitas; Daniel Sur; Luis Claudio Amendola; Masoumeh Gharib; Amine Kallala; Indu Arun; Farid Azmoudeh-Ardalan; Luciana Fujimoto; Shi Wei Liu; Huang Chun Lien; Pawan Kirtani; Marcelo Balancin; Hicham El Attar; Wenxian Yang; I. Chun Chen; Veronica Bautista; Jose Fernando Do Prado Moura; Carlos Castaneda; Eunice Spengler; Gabriela Acosta-Haab; Isabel Frahm; Joselyn Sanchez; Miluska Castillo; Najat Bouchmaa; Reena R. Md Zin; Ruohong Shui; Timothy Onyuma; Wentao Yang; Zaheed Husain; Karen Willard-Gallo; An Coosemans; Edith A. Perez; Elena Provenzano; Paula Gonzalez Ericsson; Eduardo Richardet; Ravi Mehrotra; Sandra Sarancone; Anna Ehinger; David L. Rimm; John M.S. Bartlett; International Immuno-Oncology Biomarker Working Group; Loes Kooreman

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^*, Harry R. Haynes, Elizabeth Blackley, Susan Fineberg, Jeffrey Shear, Sophia Turner, Juliana Ribeiro de Freitas, Daniel Sur, Luis Claudio Amendola, Masoumeh Gharib, Amine Kallala, Indu Arun, Farid Azmoudeh-Ardalan, Luciana Fujimoto, Shi Wei Liu, Huang Chun Lien, Pawan Kirtani, Marcelo Balancin, Hicham El Attar, Wenxian YangI. Chun Chen, Veronica Bautista, Jose Fernando Do Prado Moura, Carlos Castaneda, Eunice Spengler, Gabriela Acosta-Haab, Isabel Frahm, Joselyn Sanchez, Miluska Castillo, Najat Bouchmaa, Reena R. Md Zin, Ruohong Shui, Timothy Onyuma, Wentao Yang, Zaheed Husain, Karen Willard-Gallo, An Coosemans, Edith A. Perez, Elena Provenzano, Paula Gonzalez Ericsson, Eduardo Richardet, Ravi Mehrotra, Sandra Sarancone, Anna Ehinger, David L. Rimm, John M.S. Bartlett, International Immuno-Oncology Biomarker Working Group, Loes Kooreman

^*Corresponding author for this work

Research output: Contribution to journal › (Systematic) Review article › peer-review

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.

Original language	English
Article number	150
Number of pages	17
Journal	npj Breast Cancer
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41523-021-00346-1
Publication status	Published - 1 Dec 2021

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Cite this

El Bairi, K., Haynes, H. R., Blackley, E., Fineberg, S., Shear, J., Turner, S., de Freitas, J. R., Sur, D., Amendola, L. C., Gharib, M., Kallala, A., Arun, I., Azmoudeh-Ardalan, F., Fujimoto, L., Liu, S. W., Lien, H. C., Kirtani, P., Balancin, M., El Attar, H., ... Kooreman, L. (2021). The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group. npj Breast Cancer, 7(1), Article 150. https://doi.org/10.1038/s41523-021-00346-1

@article{7f22f47c4a3546afbbd77a53f12dda3b,

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

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.",

author = "{El Bairi}, Khalid and Haynes, {Harry R.} and Elizabeth Blackley and Susan Fineberg and Jeffrey Shear and Sophia Turner and {de Freitas}, {Juliana Ribeiro} and Daniel Sur and Amendola, {Luis Claudio} and Masoumeh Gharib and Amine Kallala and Indu Arun and Farid Azmoudeh-Ardalan and Luciana Fujimoto and Liu, {Shi Wei} and Lien, {Huang Chun} and Pawan Kirtani and Marcelo Balancin and {El Attar}, Hicham and Wenxian Yang and Chen, {I. Chun} and Veronica Bautista and {Do Prado Moura}, {Jose Fernando} and Carlos Castaneda and Eunice Spengler and Gabriela Acosta-Haab and Isabel Frahm and Joselyn Sanchez and Miluska Castillo and Najat Bouchmaa and {Md Zin}, {Reena R.} and Ruohong Shui and Timothy Onyuma and Wentao Yang and Zaheed Husain and Karen Willard-Gallo and An Coosemans and Perez, {Edith A.} and Elena Provenzano and Ericsson, {Paula Gonzalez} and Eduardo Richardet and Ravi Mehrotra and Sandra Sarancone and Anna Ehinger and Rimm, {David L.} and Bartlett, {John M.S.} and {International Immuno-Oncology Biomarker Working Group} and Loes Kooreman",

note = "Funding Information: Shom Goel{\textquoteright} work is supported by the National Health and Medical Research Council of Australia (Investigator Grant GNT1177357 to S.G.); Susan G. Komen for the Cure (CCR18547966 to S.G.); the Royal Australasian College of Physicians (Research Establishment Fellowship to S.G.); and the NIH/NCI (P50 CA168504 to S.G.). Sherene Loi is supported by the National Breast Cancer Foundation of Australia Endowed Chair and the Breast Cancer Research Foundation, New York. Khalid El Bairi would like to report that the content of this review reflects the authors{\textquoteright} perspectives and not of his institution and/or affiliation. Roberto Salgado is supported by the Breast Cancer Research Foundation (BCRF, grant N° 17-194). Funding Information: In the United States, the PD-L1 SP142 assay has been approved as a companion assay for the selection of patients with TNBC to offer atezolizumab and taxane chemotherapy (http://www.svfp.se/ foreningar/uploads/L15178/kvast/brostpatologi/Brostjuni2020.pdf). In Brazil, some central pathology laboratories perform PD-L1 testing based on principal investigator-sponsored agreements. PD-L1 IHC is tested mostly in private institutions with some programs offering pro bono testing to assess eligibility for approved ICI. The Brazilian Pathology Society follows WHO recommendations; hence the inclusion of TILs in daily practice can be envisaged in the near future. In Chile, PD-L1 testing is available on several platforms but their cost is high and this is not covered by public health insurance which covers 75% of the population. Anti-PD-L1 drugs remain at a high cost and are usually only funded by additional insurance or in clinical trial settings. In Argentina, PD-L1 testing is not covered by public funds. A few central private pathology laboratories perform PD-L1 testing on-demand funded by industry. Some pathologists have started to incorporate TILs into pathology reports for TNBC; however, there are no current national guidelines. In Per{\'u}, TILs evaluation has been included in TNBC protocols by pathologists in public and private centers. SP142 IHC is available in a few private labs while Dako 22C3 is being processed for non-breast malignancies in private and public centers. There are a few BC patients who have received atezolizumab funded via private insurance or clinical trials. It is not expected that the public system will support anti-PD-1 drugs in the near future. Publisher Copyright: {\textcopyright} 2021, The Author(s).",

year = "2021",

month = dec,

day = "1",

doi = "10.1038/s41523-021-00346-1",

language = "English",

volume = "7",

journal = "npj Breast Cancer",

issn = "2374-4677",

publisher = "Nature Publishing Group",

number = "1",

}

El Bairi, K, Haynes, HR, Blackley, E, Fineberg, S, Shear, J, Turner, S, de Freitas, JR, Sur, D, Amendola, LC, Gharib, M, Kallala, A, Arun, I, Azmoudeh-Ardalan, F, Fujimoto, L, Liu, SW, Lien, HC, Kirtani, P, Balancin, M, El Attar, H, Yang, W, Chen, IC, Bautista, V, Do Prado Moura, JF, Castaneda, C, Spengler, E, Acosta-Haab, G, Frahm, I, Sanchez, J, Castillo, M, Bouchmaa, N, Md Zin, RR, Shui, R, Onyuma, T, Yang, W, Husain, Z, Willard-Gallo, K, Coosemans, A, Perez, EA, Provenzano, E, Ericsson, PG, Richardet, E, Mehrotra, R, Sarancone, S, Ehinger, A, Rimm, DL, Bartlett, JMS, International Immuno-Oncology Biomarker Working Group & Kooreman, L 2021, 'The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group', npj Breast Cancer, vol. 7, no. 1, 150. https://doi.org/10.1038/s41523-021-00346-1

TY - JOUR

T1 - The tale of TILs in breast cancer

T2 - A report from The International Immuno-Oncology Biomarker Working Group

AU - El Bairi, Khalid

AU - Haynes, Harry R.

AU - Blackley, Elizabeth

AU - Fineberg, Susan

AU - Shear, Jeffrey

AU - Turner, Sophia

AU - de Freitas, Juliana Ribeiro

AU - Sur, Daniel

AU - Amendola, Luis Claudio

AU - Gharib, Masoumeh

AU - Kallala, Amine

AU - Arun, Indu

AU - Azmoudeh-Ardalan, Farid

AU - Fujimoto, Luciana

AU - Liu, Shi Wei

AU - Lien, Huang Chun

AU - Kirtani, Pawan

AU - Balancin, Marcelo

AU - El Attar, Hicham

AU - Yang, Wenxian

AU - Chen, I. Chun

AU - Bautista, Veronica

AU - Do Prado Moura, Jose Fernando

AU - Castaneda, Carlos

AU - Spengler, Eunice

AU - Acosta-Haab, Gabriela

AU - Frahm, Isabel

AU - Sanchez, Joselyn

AU - Castillo, Miluska

AU - Bouchmaa, Najat

AU - Md Zin, Reena R.

AU - Shui, Ruohong

AU - Onyuma, Timothy

AU - Yang, Wentao

AU - Husain, Zaheed

AU - Willard-Gallo, Karen

AU - Coosemans, An

AU - Perez, Edith A.

AU - Provenzano, Elena

AU - Ericsson, Paula Gonzalez

AU - Richardet, Eduardo

AU - Mehrotra, Ravi

AU - Sarancone, Sandra

AU - Ehinger, Anna

AU - Rimm, David L.

AU - Bartlett, John M.S.

AU - International Immuno-Oncology Biomarker Working Group

AU - Kooreman, Loes

N1 - Funding Information: Shom Goel’ work is supported by the National Health and Medical Research Council of Australia (Investigator Grant GNT1177357 to S.G.); Susan G. Komen for the Cure (CCR18547966 to S.G.); the Royal Australasian College of Physicians (Research Establishment Fellowship to S.G.); and the NIH/NCI (P50 CA168504 to S.G.). Sherene Loi is supported by the National Breast Cancer Foundation of Australia Endowed Chair and the Breast Cancer Research Foundation, New York. Khalid El Bairi would like to report that the content of this review reflects the authors’ perspectives and not of his institution and/or affiliation. Roberto Salgado is supported by the Breast Cancer Research Foundation (BCRF, grant N° 17-194). Funding Information: In the United States, the PD-L1 SP142 assay has been approved as a companion assay for the selection of patients with TNBC to offer atezolizumab and taxane chemotherapy (http://www.svfp.se/ foreningar/uploads/L15178/kvast/brostpatologi/Brostjuni2020.pdf). In Brazil, some central pathology laboratories perform PD-L1 testing based on principal investigator-sponsored agreements. PD-L1 IHC is tested mostly in private institutions with some programs offering pro bono testing to assess eligibility for approved ICI. The Brazilian Pathology Society follows WHO recommendations; hence the inclusion of TILs in daily practice can be envisaged in the near future. In Chile, PD-L1 testing is available on several platforms but their cost is high and this is not covered by public health insurance which covers 75% of the population. Anti-PD-L1 drugs remain at a high cost and are usually only funded by additional insurance or in clinical trial settings. In Argentina, PD-L1 testing is not covered by public funds. A few central private pathology laboratories perform PD-L1 testing on-demand funded by industry. Some pathologists have started to incorporate TILs into pathology reports for TNBC; however, there are no current national guidelines. In Perú, TILs evaluation has been included in TNBC protocols by pathologists in public and private centers. SP142 IHC is available in a few private labs while Dako 22C3 is being processed for non-breast malignancies in private and public centers. There are a few BC patients who have received atezolizumab funded via private insurance or clinical trials. It is not expected that the public system will support anti-PD-1 drugs in the near future. Publisher Copyright: © 2021, The Author(s).

PY - 2021/12/1

Y1 - 2021/12/1

N2 - 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.

AB - 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.

U2 - 10.1038/s41523-021-00346-1

DO - 10.1038/s41523-021-00346-1

M3 - (Systematic) Review article

SN - 2374-4677

VL - 7

JO - npj Breast Cancer

JF - npj Breast Cancer

IS - 1

M1 - 150

ER -