Report on computational assessment of Tumor Infiltrating Lymphocytes from the International Immuno-Oncology Biomarker Working Group
Authors: Amgad Mohamed , Stovgaard Elisabeth Specht , Balslev Eva , Thagaard Jeppe , Chen Weijie , Dudgeon Sarah , Sharma Ashish , Kerner Jennifer K. , Denkert Carsten , Yuan Yinyin , AbdulJabbar Khalid , Wienert Stephan , Savas Peter , Voorwerk Leonie , Beck Andrew H. , Madabhushi Anant , Hartman Johan , Sebastian Manu M. , Horlings Hugo M. , Hudeček Jan , Ciompi Francesco , Moore David A. , Singh Rajendra , Roblin Elvire , Balancin Marcelo Luiz , Mathieu Marie-Christine , Lennerz Jochen K. , Kirtani Pawan , Chen I-Chun , Braybrooke Jeremy P. , Pruneri Giancarlo , Demaria Sandra , Adams Sylvia , Schnitt Stuart J. , Lakhani Sunil R. , Rojo Federico , Comerma Laura , Badve Sunil S. , Khojasteh Mehrnoush , Symmans W. Fraser , Sotiriou Christos , Gonzalez-Ericsson Paula , Pogue-Geile Katherine L. , Kim Rim S. , Rimm David L. , Viale Giuseppe , Hewitt Stephen M. , Bartlett John M. S. , Penault-Llorca Frédérique , Goel Shom , Lien Huang-Chun , Loibl Sibylle , Kos Zuzana , Loi Sherene , Hanna Matthew G. , Michiels Stefan , Kok Marleen , Nielsen Torsten O. , Lazar Alexander J. , Bago-Horvath Zsuzsanna , Kooreman Loes F. S. , van der Laak Jeroen A. W. M. , Saltz Joel , Gallas Brandon D. , Kurkure Uday , Barnes Michael , Salgado Roberto , Cooper Lee A. D. ,   International Immuno-Oncology Biomarker Working Group, Hyytiäinen Aini , Hida Akira I. , Thompson Alastair , Lefevre Alex , Gown Allen , Lo Amy , Sapino Anna , Moreira Andre , Richardson Andrea , Vingiani Andrea , Bellizzi Andrew M. , Tutt Andrew , Guerrero-Zotano Angel , Grigoriadis Anita , Ehinger Anna , Garrido-Castro Anna C. , Vincent-Salomon Anne , Laenkholm Anne-Vibeke , Cimino-Mathews Ashley , Srinivasan Ashok , Acs Balazs , Singh Baljit , Calhoun Benjamin , Haibe-Kans Benjamin , Solomon Benjamin , Thapa Bibhusal , Nelson Brad H. , Castaneda Carlos , Ballesteroes-Merino Carmen , Criscitiello Carmen , Boeckx Carolien , Colpaert Cecile , Quinn Cecily , Chennubhotla Chakra S. , Swanton Charles , Solinas Cinzia , Hiley Crispin , Drubay Damien , Bethmann Daniel , Dillon Deborah A. , Larsimont Denis , Sabanathan Dhanusha , Peeters Dieter , Zardavas Dimitrios , Höflmayer Doris , Johnson Douglas B. , Thompson E. Aubrey , Brogi Edi , Perez Edith , ElGabry Ehab A. , Blackley Elizabeth F. , Reisenbichler Emily , Bellolio Enrique , Chmielik Ewa , Gaire Fabien , Andre Fabrice , Lu Fang-I , Azmoudeh-Ardalan Farid , Gruosso Forbius Tina , Peale Franklin , Hirsch Fred R. , Klaushen Frederick , Acosta-Haab Gabriela , Farshid Gelareh , van den Eynden Gert , Curigliano Giuseppe , Floris Giuseppe , Broeckx Glenn , Koeppen Harmut , Haynes Harry R. , McArthur Heather , Joensuu Heikki , Olofsson Helena , Cree Ian , Nederlof Iris , Frahm Isabel , Brcic Iva , Chan Jack , Hall Jacqueline A. , Ziai James , Brock Jane , Wesseling Jelle , Giltnane Jennifer , Lemonnier Jerome , Zha Jiping , M. Ribeiro Joana , Carter Jodi M. , Hainfellner Johannes , Quesne John Le , Juco Jonathan W. , Reis-Filho Jorge , van den Berg Jose , Sanchez Joselyn , Sparano Joseph , Cucherousset Joël , Araya Juan Carlos , Adam Julien , Balko Justin M. , Saeger Kai , Siziopikou Kalliopi , Willard-Gallo Karen , Sikorska Karolina , Weber Karsten , Steele Keith E. , Emancipator Kenneth , El Bairi Khalid , Blenman Kim R. M. , Allison Kimberly H. , van de Vijver Koen K. , Korski Konstanty , Pusztai Lajos , Buisseret Laurence , Shi Leming , Shi-wei Liu , Molinero Luciana , Estrada M. Valeria , van Seijen Maartje , Lacroix-Triki Magali , Cheang Maggie C. U. , Bakir Maise al , van de Vijver Marc , Dieci Maria Vittoria , Rebelatto Marlon C. , Piccart Martine , Goetz Matthew P. , Preusser Matthias , Sanders Melinda E. , Regan Meredith M. , Christie Michael , Misialek Michael , Ignatiadis Michail , de Maaker Michiel , van Bockstal Mieke , Castillo Miluska , Harbeck Nadia , Tung Nadine , Laudus Nele , Sirtaine Nicolas , Burchardi Nicole , Ternes Nils , Radosevic-Robin Nina , Gluz Oleg , Grimm Oliver , Nuciforo Paolo , Jank Paul , Jelinic Petar , Watson Peter H. , Francis Prudence A. , Russell Prudence A. , Pierce Robert H. , Hills Robert , Leon-Ferre Roberto , de Wind Roland , Shui Ruohong , Declercq Sabine , Leung Sam , Tabbarah Sami , Souza Sandra C. , O’Toole Sandra , Swain Sandra , Willis Scooter , Ely Scott , Kim Seong- Rim , Bedri Shahinaz , Irshad Sheeba , Liu Shi-Wei , Hendry Shona , Bianchi Simonetta , Bragança Sofia , Paik Soonmyung , Fox Stephen B. , Luen Stephen J. , Naber Stephen , Luz Sua , Fineberg Susan , Soler Teresa , Gevaert Thomas , d’Alfons Timothy , John Tom , Sugie Tomohagu , Bossuyt Veerle , Manem Venkata , Cámaea Vincente Peg , Tong Weida , Yang Wentao , Tran William T. , Wang Yihong , Allory Yves , Husain Zaheed 
Published: May 2020

AbstractAssessment 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.