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

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.

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© The Author(s) 2020.

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Competing interestsJ.T. is funded by Visiopharm A/S, Denmark. A.M. is an equity holder in Elucid Bioimaging and in Inspirata Inc. He is also a scientific advisory consultant for Inspirata Inc. In addition he has served as a scientific advisory board member for Inspirata Inc, Astrazeneca, Bristol Meyers-Squibb and Merck. He also has sponsored research agreements with Philips and Inspirata Inc. His technology has been licensed to Elucid Bioimaging and Inspirata Inc. He is also involved in an NIH U24 grant with PathCore Inc, and three different R01 grants with Inspirata Inc. S.R.L. received travel and educational funding from Roche/Ventana. A.J.L. serves as a consultant for BMS, Merck, AZ/Medimmune, and Genentech. He is also provides consulting and advisory work for many other companies not relevant to this work. FPL does consulting for Astrazeneca, BMS, Roche, MSD Pfizer, Novartis, Sanofi, and Lilly. S.Ld.H., A.K., M.K., U.K., and M.B. are employees of Roche. J.M.S.B. is consultant for Insight Genetics, BioNTech AG, Biothernostics, Pfizer, RNA Diagnostics, and OncoXchange. He received funding from Thermo Fisher Scientific, Genoptix, Agendia, NanoString technologies, Stratifyer GmBH, and Biotheranostics. L.F.S.K. is a consultant for Roche and Novartis. J.K.K. and A.H.B. are employees of PathAI. D.L.R. is on the advisory board for Amgen, Astra Xeneca, Cell Signaling Technology, Cepheid, Daiichi Sankyo, GSK, Konica/Minolta, Merck, Nanostring, Perking Elmer, Roche/Ventana, and Ultivue. He has received research support from Astrazeneca, Cepheid, Navigate BioPharma, NextCure, Lilly, Ultivue, Roche/Ventana, Akoya/Perkin Elmer, and Nanostring. He also has financial conflicts of interest with BMS, Biocept, PixelGear, and Rarecyte. S.G. is a consultant for and/or receives funding from Eli Lilly, Novartis, and G1 Therapeutics. J.A.W.M.vdL. is a member of the scientific advisory boards of Philips, the Netherlands and ContextVision, Sweden, and receives research funding from Philips, the Netherlands and Sectra, Sweden. S.A. is a consultant for Merck, Genentech, and BMS, and receives funding from Merck, Genentech, BMS, Novartis, Celgene, and Amgen. T.O.N. has consulted for Nanostring, and has intellectual property rights and ownership interests from Bioclassifier LLC. S.L. receives research funding to her institution from Novartis, Bristol Meyers-Squibb, Merck, Roche-Genentech, Puma Biotechnology, Pfizer and Eli Lilly. She has acted as consultant (not compensated) to Seattle Genetics, Pfizer, Novartis, BMS, Merck, AstraZeneca and Roche-Genentech. She has acted as consultant (paid to her institution) to Aduro Biotech. J.H. is director and owner of Slide Score BV. M.M.S. is a medical advisory board member of OptraScan. R.S. has received research support from Merck, Roche, Puma; and travel/congress support from AstraZeneca, Roche and Merck; and he has served as an advisory board member of BMS and Roche and consults for BMS.