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The tale of TILs in breast cancer: A report from The International Immuno-Oncology Biomarker Working Group
Khalid El Bairi, Harry R. Haynes, Elizabeth F. 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 Botinelly Mendonça Fujimoto, Luz F. Sua, Shiwei Liu, Huang‐Chun Lien, Pawan Kirtani, Marcelo Balancin, H. El Attar, Prerna Guleria, Wenxian Yang, Emad Shash, I‐Chun Chen, Verónica Bautista, José Fernando do Prado Moura, 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 Perez, Elena Provenzano, Eduardo Richardet, Ravi Mehrotra, Sandra Sarancone, Anna Ehinger, David L. Rimm, John M.S. Bartlett, Giuseppe Viale, Carsten Denkert, Akira I. Hida, Christos Sotiriou, Sibylle Loibl, Stephen M. Hewitt, Sunil Badve, W. Fraser Symmans, Rim S. Kim, Giancarlo Pruneri, Shom Goel, Prudence A. Francis, Gloria Inurrigarro, Rin Yamaguchi, Hernán Garcı́a Rivello, Hugo M. Horlings, Saïd Afqir, Roberto Salgado, Sylvia Adams, Marleen Kok, Stefan Michiels, Sandra Demaria, Sherene Loi, Jeffrey Shear, Luis Claudio Amendola, Farid Azmoudeh-Ardalan, Hicham El Attar, Veronica Bautista, Gabriela Acosta‐Haab, Ruohong Shui, Sandra Sarancone, Carsten Denkert, Stefan Michiels, Sherene Loi, Vera Schelfhout, Elham Arbzadeh, Anastasiya Bondanar, Silvio Antonio Galeano Reyes, José Ramírez Ruz, Jun Kang, Xiang Lü, Martina Zimovjanová, Pilar Togores, Tülin Öztürk, Asawari Patil, Marcus Corpa, Ann Whitehouse, Benjamin Tan, Alfredo de Paula, Claudia Rossetti, Corinna Lang‐Schwarz, Sarah Mahon, Cinzia Giacometti, Barbro Linderholm, Frederik Deman, Giacomo Montagna, Gyungyub Gong, Marta Pavcovich, Yeesoo Chaer, Isabel Alvarado Cabrero, Mayana Lopes de Brito, Nevena Ilieva, Annamaria Fulop, Maiara Priscilla de Souza, Domenico Bilancia, Michael Idowu, Ritika Johri, Joanna Szpor, Lira Bachani, Fernando Schmitt, Mag Giannotti, Yutaka Kurebayashi, Eduardo Salido, Laura Bortesi, Sara Bonetto, Kevin Elomina, Patricia López, Vijay Sharma, Amalika Edirisinghe, Dhanvi Mathur, Ayushi Sahay, Makhlouf Ait Mouloud, Chau Giang, Edwin Mukolwe, Edgar Kiruka, Nancy L. Samberg, Norie Abe, Mark Brown, Ewan K.A. Millar, Xiaoxian Li, Yuan Zheng, Asokan Pasupathy, Raffaele Miele, Ronald D. Luff, Mônica Modesto Araújo e Porfírio, Ogugua Ajemba, Rashida Soni, Enrico Orvieto, Michael DiMaio, Jeremy Thomas, Reena Merard, Manish Mani Subramaniam, Thiago Apolinario, Ovidiu Preda, Ricardo Preda, Alexander Makanga, Marcelo do Rego Maciel Souto Maior, Lingyu Li, Mahasti Saghatchian, Tricia Saurine, Emiel A. M. Janssen, John H. Cochran, Nikitina Vlada, Rocco Cappellesso, Katherine Elfer, Morven Hollick, Sangeeta Desai, Gizem Öner, A. J. M. Schreurs, Steve Liu, Rashindrie Perera, Paola Mercurio, Felip Garcia, Kareem Hosny, Hirofumi Matsumoto, Carolien van Deurzen, Giampaolo Bianchini, İpek Çoban, Arif Jahangir, Arman Rahman, Daniel G. Stover, Paulo Luz, Anne Martel, Yannick Waumans, Albrecht Stenzinger, Javier Cortes, Polina Dimitrova, Inne Nauwelaers, Montse Velasco, Fang Fan, Güray Aktürk, Michael Firer, Ioannis Roxanis, Mary Schneck, Hannah Y. Wen, Vincent Cockenpot, Aleksei Konstantinov, Ana Calatrava, M. N. Vidya, Hyun Joo Choi, Paul Jank, Aini Hyyti ÇÏinen, Dhanusha Sabanathan, Giuseppe Floris, Doris Hoeflmayer, Tetsuo Hamada, Nele Laudus, Anita Grigoriadis, Ilaria Porcellato, Balázs Ács, Federica Miglietta, Jeannette Parrodi, David Clunie, Benjamin C. Calhoun, Fang‐I Lu, Alexis Lefevre, Sami Tabbarah, William T. Tran, Isaac García-Murillas, Petar Jelinic, Carolien Boeckx, Sandra C. Souza, MarÇða Cebollero, E. Felip, Jose Luis Solorzano Rendon, Ehab El Gabry, Joel Saltz, Emilio Bria, Giovanna Garufi, Johan Hartman, Manu Sebastian, Helena Olofsson, Loes Kooreman, Joël Cucherousset, Marie‐Christine Mathieu, Carmen Ballesteros‐Merino, Popi Siziopikou, Jacinta J Fong, Molly Klein, Ignasi Roig I. Qulis, Jelle Wesseling, Enrique Bellolio, Juan Carlos Araya, Stephen P. Naber, Maggie Cheang, Isabella Castellano, Ales Ales, Anne‐Vibeke Lænkholm, Janina Kulka, Cecily Quinn, Anna Sapino, Isabel Amendoeira, Caterina Marchiò, Jeremy Braybrooke, Anne Vincent-Salomon, Konstanty Korski, Michail Sofopoulos, Elisabeth Ida Specht Stovgaard, Simonetta Bianchi, Zsuzsanna Bagó-Horváth, Clare Yu, Peter Regitnig, Sean R. R. Hall, Zuzana Kos, Sneha Sant, Jean‐Christophe Tille, Brandon D. Gallas, Daniel Bethmann, Peter Savas, Larissa Mendes, Teresa Soler, Maartje van Seijen, Tina Gruosso, Angela Quintana, Jennifer M. Giltnane, Gert Van den Eynden, Eleonora Duregon, Rafael de Cabo, Phil Coates Recamo, Louis Gaboury, Johannes Zimmerman, C. Stanciu Pop, Alejandra Wernicke, David Williams, Anthony J. Gill, Benjamin Solomon, Bibhusal Thapa, Gelareh Farshid, Leslie Gilham, Michael Christie, Sandra A. O’Toole, Shona Hendry, Stephen B. Fox, Stephen J. Luen, Sunil R. Lakhani, Talia L. Fuchs, Iva Brčić, Johannes A. Hainfellner, Sigurd Lax, Matthias Preusser, Philip Poortmans, Alex Decaluwe, Caroline Carey, Cécile Colpaert, Denis Larsimont, Dieter Peeters, Glenn Broeckx, Koen Van de Vijver, Laurence Buisseret, Luc Dirix, Marjan Hertoghs, Martine Piccart, Michail Ignatiadis, Mieke Van Bockstal, Nicolas Sirtaine, Peter Vermeulen, Roland de Wind, Sabine Declercq, Thomas Gevaert, Benjamin Haibe-Kans, Brad H. Nelson, Peter H. Watson, Sam Leung, Torsten O. Nielsen, Leming Shi, Eva Balslev, Jeppe Thagaard, Alhadi Almangush, Antti Mäkitie, Heikki Joensuu, Johan Lundin, Damien Drubay, Elvire Roblin, Fabrice André, Frédérique Penault‐Llorca, Jérôme Lemonnier, Julien Adam, Magali Lacroix‐Triki, Nils Ternès, Nina Radosevic‐Robin, Frederick Klaushen, Karsten E. Weber, Nadia Harbeck, Oleg Gluz, Stephan Wienert, Gábor Cserni, Andrea Vingiani, Carmen Criscitiello, Cinzia Solinas, Giuseppe Curigliano, Eiichi Konishi, Eiji Suzuki, Katsuhiro Yoshikawa, Kosuke Kawaguchi, Masahiro Takada, Masakazu Toi, Mitsuaki Ishida, Nobuhiro Shibata, Shigehira Saji, Takahiro Kogawa, Takashi Sakatani, Takeru Okamoto, Takuya Moriya, Tatsuki R. Kataoka, Tatsunori Shimoi, Tomohagu Sugie, Tomoharu Sugie, Toru Mukohara, Shu Yazaki, Yuichiro Kikawa, Yuji Kozuka, Shahin Sayed, Reena Rahayu, Reena Ramsaroop, Elżbieta Senkus, Ewa Chmielik, Fátima Cardoso, Joana Ribeiro, Jack Junjie Chan, Rebecca Dent, Miguel Martín, Carlos Hagen, Ángel Guerrero, Federico Rojo, Laura Comerma, Paolo Nucíforo, Victor Vivo Serrano, Vincente Peg Cámaea, Tessa G. Steenbruggen, Francesco Ciompi, Iris Nederlof, Jeroen van der Laak, José van den Berg, Leonie Voorwerk, Michiel de Maaker, Sabine C. Linn, Hayley McKenzie, Navita Somaiah, Andrew Tutt, Charles Swanton, Crispin T. Hiley, David A. Moore, Jacqueline A. Hall, John Le Quesne, Khalid Abdul Jabbar, Maise Al Bakir, Robert K. Hills, Sheeba Irshad, Yinyin Yuan, Zaibo Li, Minetta C. Liu, Jonathan Klein, Oluwole Fadare, Alastair M. Thompson, Alexander J. Lazar, Allen M. Gown, Ana C. Garrido Castro, Anant Madabhushi, André Moreira, Andrea L. Richardson, Andrew H. Beck, Andrew M. Bellizzi, Antonio C. Wolff, Aparna Harbhajanka, Ashish Sharma, Ashley Cimino‐Mathews, Ashok Srinivasan, Baljit Singh, Chakra S. Chennubhotla, Cynthia Chauhan, Deborah Dillon, Dimitrios Zardavas, Douglas B. Johnson, Aubrey Thompson, Edi Brogi, Emily Reisenbichler, Erich Huang, Fred R. Hirsch, Heather L. McArthur, James Ziai, Jane Brock, Jennifer K. Kerner, Jiping Zha, Jochen K. Lennerz, Jodi M. Carter, Jorge S. Reis‐Filho, Joseph A. Sparano, Justin M. Balko, Katherine L. Pogue–Geile, Keith E. Steele, Kim Blenman, Kimberly H. Allison, Lajos Pusztai, Lee Cooper, Valeria M. Estrada, Margaret Flowers, Mark E. Robson, Marlon C. Rebelatto, Matthew G. Hanna, Matthew P. Goetz, Mehrnoush Khojasteh, Melinda E. Sanders, Meredith M. Regan, Michael J. Misialek, Mohamed Amgad, Nadine Tung, Richard S.P. Huang, Robert H. Pierce, Roberto A. Leon‐Ferre, Sandra M. Swain, Scott Ely, Seong-Rim Kim, Shahinaz Bedri, Soonmyung Paik, Stuart J. Schnitt, Timothy d’Alfons, Uday Kurkure, Veerle Bossuyt, Weida Tong, Yihong Wang, Carlos Henrique dos Anjos, Fabien Gaire, Paul J. van Diest
Bibliographic record
Venuenpj Breast Cancer · 2021
Typereview
Languageen
FieldMedicine
TopicCancer Immunotherapy and Biomarkers
Canadian institutionsCentre for Advancing Health OutcomesUniversity of British ColumbiaUniversité de MontréalHealth Sciences CentreSunnybrook Health Science CentrePrincess Margaret Cancer CentreBC Cancer AgencyUniversity of TorontoOntario Institute for Cancer Research
FundersMedical Research CouncilNational Cancer InstituteCancer Research UKNational Institutes of HealthNational Breast Cancer FoundationNational Center for Advancing Translational SciencesRoyal Australasian College of PhysiciansNational Health and Medical Research CouncilBreast Cancer Research Foundation
KeywordsOncologyImmunotherapyBreast cancerMedicineTumor-infiltrating lymphocytesBiomarkerInternal medicineImmune checkpointCancerClinical OncologyTriple-negative breast cancerBiology
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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Review · Consensus signal: Review
Teacher disagreement score0.002
Threshold uncertainty score0.007
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
Opus teacher head0.042
GPT teacher head0.363
Teacher spread0.321 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
The models applied no category: nothing in the taxonomy fit this work.
Study designNot applicable
Domainnot available
GenreReview
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".
Quick stats
Citations275
Published2021
Admission routes1
Has abstractyes