The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group
Authors: El Bairi Khalid , Haynes Harry R. , Blackley Elizabeth , Fineberg Susan , Shear Jeffrey , Turner Sophia , de Freitas Juliana Ribeiro , Sur Daniel , Amendola Luis Claudio , Gharib Masoumeh , Kallala Amine , Arun Indu , Azmoudeh-Ardalan Farid , Fujimoto Luciana , Sua Luz F. , Liu Shi-Wei , Lien Huang-Chun , Kirtani Pawan , Balancin Marcelo , El Attar Hicham , Guleria Prerna , Yang Wenxian , Shash Emad , Chen I-Chun , Bautista Veronica , Do Prado Moura Jose Fernando , Rapoport Bernardo L. , Castaneda Carlos , Spengler Eunice , Acosta-Haab Gabriela , Frahm Isabel , Sanchez Joselyn , Castillo Miluska , Bouchmaa Najat , Md Zin Reena R. , Shui Ruohong , Onyuma Timothy , Yang Wentao , Husain Zaheed , Willard-Gallo Karen , Coosemans An , Perez Edith A. , Provenzano Elena , Ericsson Paula Gonzalez , Richardet Eduardo , Mehrotra Ravi , Sarancone Sandra , Ehinger Anna , Rimm David L. , Bartlett John M. S. , Viale Giuseppe , Denkert Carsten , Hida Akira I. , Sotiriou Christos , Loibl Sibylle , Hewitt Stephen M. , Badve Sunil , Symmans William Fraser , Kim Rim S. , Pruneri Giancarlo , Goel Shom , Francis Prudence A. , Inurrigarro Gloria , Yamaguchi Rin , Garcia-Rivello Hernan , Horlings Hugo , Afqir Said , Salgado Roberto , Adams Sylvia , Kok Marleen , Dieci Maria Vittoria , Michiels Stefan , Demaria Sandra , Loi Sherene ,   The International Immuno-Oncology Biomarker Working Group, El Bairi Khalid , Haynes Harry R. , Blackley Elizabeth , Fineberg Susan , Shear Jeffrey , Turner Sophia , de Freitas Juliana Ribeiro , Sur Daniel , Amendola Luis Claudio , Gharib Masoumeh , Kallala Amine , Arun Indu , Azmoudeh-Ardalan Farid , Fujimoto Luciana , Sua Luz F. , Liu Shi-Wei , Lien Huang-Chun , Kirtani Pawan , Balancin Marcelo , El Attar Hicham , Guleria Prerna , Yang Wenxian , Shash Emad , Chen I-Chun , Bautista Veronica , Do Prado Moura Jose Fernando , Rapoport Bernardo L. , Castaneda Carlos , Spengler Eunice , Acosta-Haab Gabriela , Frahm Isabel , Sanchez Joselyn , Castillo Miluska , Bouchmaa Najat , Md Zin Reena R. , Shui Ruohong , Onyuma Timothy , Yang Wentao , Husain Zaheed , Willard-Gallo Karen , Coosemans An , Perez Edith A. , Provenzano Elena , Ericsson Paula Gonzalez , Richardet Eduardo , Mehrotra Ravi , Sarancone Sandra , Ehinger Anna , Rimm David L. , Bartlett John M. S. , Viale Giuseppe , Denkert Carsten , Hida Akira I. , Sotiriou Christos , Loibl Sibylle , Hewitt Stephen M. , Badve Sunil , Symmans William Fraser , Kim Rim S. , Pruneri Giancarlo , Goel Shom , Francis Prudence A. , Inurrigarro Gloria , Yamaguchi Rin , Garcia-Rivello Hernan , Horlings Hugo , Afqir Said , Salgado Roberto , Adams Sylvia , Kok Marleen , Dieci Maria Vittoria , Michiels Stefan , Demaria Sandra , Loi Sherene , Schelfhout Vera , Arbzadeh Elham , Bondanar Anastasiya , Reyes Silvio Antonio Galeano , Ruz Jose Ramirez , Kang Jun , Xiang Lu , Zimovjanova Martina , Togores Pilar , Ozturk Tulin , Patil Asawari , Corpa Marcus , Whitehouse Ann , Tan Benjamin , de Paula Alfredo , Rossetti Claudia , Lang-Schwarz Corinna , Mahon Sarah , Giacometti Cinzia , Linderholm Barbro , Deman Frederik , Montagna Giacomo , Gong Gyungyub , Pavcovich Marta , Chaer Yeesoo , Cabrero Isabel Alvarado , de Brito Mayana Lopes , Ilieva Nevena , Fulop Annamaria , Souza Maiara , Bilancia Domenico , Idowu Michael , Johri Ritika , Szpor Joanna , Bachani Lira , Schmitt Fernando , Giannotti Mag , Kurebayashi Yutaka , Ramirez Bruno Elias Anota , Salido Eduardo , Bortesi Laura , Bonetto Sara , Elomina Kevin , Lopez Patricia , Sharma Vijay , Edirisinghe Amalika , Mathur Dhanvi , Sahay Ayushi , Mouloud Makhlouf Ait , Giang Chau Huynh , Mukolwe Edwin , Kiruka Edgar , Samberg Nancy , Abe Norie , Brown Mark , Millar Ewan , Li Xiaoxian , Yuan Zheng , Pasupathy Asokan , Miele Raffaele , Luff Ronald , e Porfirio Monica Modesto Araujo , Ajemba Ogugua , Soni Rashida , Orvieto Enrico , DiMaio Michael , Thomas Jeremy , Merard Reena , Subramaniam Manish Mani , Apolinario Thiago , Preda Ovidiu , Preda Ricardo , Makanga Alexander , Maior Marcelo Souto , Li Lingyu , Saghatchian Mahasti , Saurine Tricia , Janssen Emiel , Cochran John , Vlada Nikitina , Cappellesso Rocco , Elfer Katherine , Hollick Morven , Desai Sangeeta , Oner Gizem , Schreurs Arthur , Liu Steve , Perera Rashindrie , Mercurio Paola , Garcia Felip , Hosny Kareem , Matsumoto Hirofumi , van Deurzen Carolien , Bianchini Giampaolo , Coban Ipek , Jahangir Arif , Rahman Arman , Stover Daniel , Luz Paulo , Martel Anne , Waumans Yannick , Stenzinger Albrecht , Cortes Javier , Dimitrova Polina , Nauwelaers Inne , Velasco Montse , Fan Fang , Akturk Guray , Firer Michael , Roxanis Ioannis , Schneck Mary , Wen Hannah , Cockenpot Vincent , Konstantinov Aleksei , Calatrava Ana , Vidya M. N. , Choi Hyun Joo , Jank Paul , ÇÏinen Aini Hyyti , Sabanathan Dhanusha , Floris Giuseppe , Hoeflmayer Doris , Hamada Tetsuo , Laudus Nele , Grigoriadis Anita , Porcellato Ilaria , Acs Balazs , Miglietta Federica , Parrodi Jeannette , Clunie David , Calhoun Benjamin , Lu Fang-I , Lefevre Alex , Tabbarah Sami , Tran William , Garcia-murillas Isaac , Jelinic Petar , Boeckx Carolien , Souza Sandra , Cebollero MarÇða , Felip Eudald , Rendon Jose Luis Solorzano , El Gabry Ehab , Saltz Joel , Bria Emilio , Garufi Giovanna , Hartman Johan , Sebastian Manu , Olofsson Helena , Kooreman Loes , Cucherousset Joël , Mathieu Marie-Christine , Ballesteros-Merino Carmen , Siziopikou Popi , Fong Jacinta , Klein Molly , Qulis Ignasi Roig I. , Wesseling Jelle , Bellolio Enrique , Araya Juan Carlos , Naber Stephen , Cheang Maggie , Castellano Isabella , Ales Ales , Laenkholm Anne-Vibeke , Kulka Janina , Quinn Cecily , Sapino Anna , Amendoeira Isabel , Marchio Caterina , Braybrooke Jeremy , Vincent-Salomon Anne , Korski Konstanty , Sofopoulos Michail , Stovgaard Elisabeth Ida Specht , Bianchi Simonetta , Bago-Horvath Zsuzsanna , Yu Clare , Regitnig Peter , Hall Sean , Kos Zuzana , Sant Sneha , Tille Jean-Christophe , Gallas Brandon , Bethmann Daniel , Savas Peter , Mendes Larissa , Soler Teresa , van Seijen Maartje , Gruosso Tina , Quintana Angela , Giltnane Jennifer , Van den Eynden Gert , Duregon Eleonora , de Cabo Rafa , Recamo Phil Coates , Gaboury Louis , Zimmerman Johannes , Pop Claudia Stanciu , Wernicke Alejandra , Williams David , Gill Anthony , Solomon Benjamin , Thapa Bibhusal , Farshid Gelareh , Gilham Leslie , Christie Michael , O’Toole Sandra , Hendry Shona , Fox Stephen B. , Luen Stephen J. , Lakhani Sunil R. , Fuchs Talia , John Tom , Brcic Iva , Hainfellner Johannes , Sigurd Lax , Preusser Matthias , Poortmans Philip , Decaluwe Alex , Carey Caroline , Colpaert Cecile , Larsimont Denis , Peeters Dieter , Broeckx Glenn , van de Vijver Koen , Buisseret Laurence , Dirix Luc , Hertoghs Marjan , Piccart Martine , Ignatiadis Michail , Van Bockstal Mieke , Sirtaine Nicolas , Vermeulen Peter , de Wind Roland , Declercq Sabine , Gevaert Thomas , Haibe-Kans Benjamin , Nelson Brad H. , Watson Peter H. , Leung Sam , Nielsen Torsten , Shi Leming , Balslev Eva , Thagaard Jeppe , Almangush Alhadi , Makitie Antti , Joensuu Heikki , Lundin Johan , Drubay Damien , Roblin Elvire , Andre Fabrice , Penault-Llorca Frederique , Lemonnier Jerome , Adam Julien , Lacroix-Triki Magali , Ternes Nils , Radosevic-Robin Nina , Klaushen Frederick , Weber Karsten , Harbeck Nadia , Gluz Oleg , Wienert Stephan , Cserni Gabor , Vingiani Andrea , Criscitiello Carmen , Solinas Cinzia , Curigliano Giuseppe , Konishi Eiichi , Suzuki Eiji , Yoshikawa Katsuhiro , Kawaguchi Kosuke , Takada Masahiro , Toi Masakazu , Ishida Mitsuaki , Shibata Nobuhiro , Saji Shigehira , Kogawa Takahiro , Sakatani Takashi , Okamoto Takeru , Moriya Takuya , Kataoka Tatsuki , Shimoi Tatsunori , Sugie Tomohagu , Sugie Tomoharu , Mukohara Toru , Shu Yazaki , Kikawa Yuichiro , Kozuka Yuji , Sayed Shahin , Rahayu Reena , Ramsaroop Reena , Senkus-Konefka Elżbieta , Chmielik Ewa , Cardoso Fatima , Ribeiro Joana , Chan Jack , Dent Rebecca , Martin Miguel , Hagen Carlos , Guerrero Angel , Rojo Federico , Comerma Laura , Nuciforo Paolo , Serrano Victor Vivo , Cámaea Vincente Peg , Steenbruggen Tessa , Ciompi Francesco , Nederlof Iris , Jan Hudecek  , van der Laak Jeroen , van den Berg Jose , Voorwerk Leonie , van de Vijver Mark , de Maaker Michiel , Linn Sabine , McKenzie Hayley , Somaiah Navita , Tutt Andrew , Swanton Charles , Hiley Crispin , Moore David A. , Hall Jacqueline A. , Le Quesne John , Jabbar Khalid Abdul , al Bakir Maise , Hills Robert , Irshad Sheeba , Yuan Yinyin , Li Zaibo , Liu Minetta , Klein Jonathan , Fadare Oluwole , Thompson Alastair , Lazar Alexander J. , Gown Allen , Lo Amy , Garrido Castro Ana C. , Madabhushi Anant , Moreira Andre , Richardson Andrea , Beck Andrew H. , Bellizzi Andrew M. , Wolff Antonio , Harbhajanka Aparna , Sharma Ashish , Cimino-Mathews Ashley , Srinivasan Ashok , Singh Baljit , Chennubhotla Chakra S. , Chauhan Cynthia , Dillon Deborah A. , Zardavas Dimitrios , Johnson Douglas B. , Thompson Aubrey E. , Brogi Edi , Reisenbichler Emily , Huang Erich , Hirsch Fred R. , McArthur Heather , Ziai James , Brock Jane , Kerner Jennifer , Zha Jiping , Lennerz Jochen K. , Carter Jodi M. , Reis-Filho Jorge , Sparano Joseph , Balko Justin M. , Pogue-Geile Katherine , Steele Keith E. , Blenman Kim R. M. , Allison Kimberly H. , Pusztai Lajos , Cooper Lee , Estrada Valeria M. , Flowers Margaret , Robson Mark , Rebelatto Marlon C. , Hanna Matthew G. , Goetz Matthew P. , Khojasteh Mehrnoush , Sanders Melinda E. , Regan Meredith M. , Misialek Michael , Amgad Mohamed , Tung Nadine , Singh Rajendra , Huang Richard , Pierce Robert H. , Leon-Ferre Roberto , Swain Sandra , Ely Scott , Kim Seong-Rim , Bedri Shahinaz , Paik Soonmyung , Schnitt Stuart , d’Alfons Timothy , Kurkure Uday , Bossuyt Veerle , Tong Weida , Wang Yihong , Dos Anjos Carlos Henrique , Gaire Fabien , Van Diest Paul J. 
Published: December 2021

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.