Cancer cell-intrinsic mechanisms driving acquired immune tolerance.

Immune evasion is a hallmark of cancer, enabling tumors to survive contact with the host immune system and evade the cycle of immune recognition and destruction. Here, we review the current understanding of the cancer cell-intrinsic factors driving immune evasion. We focus on T cells as key effectors of anti-cancer immunity and argue that cancer cells evade immune destruction by gaining control over pathways that usually serve to maintain physiological tolerance to self. Using this framework, we place recent mechanistic advances in the understanding of cancer immune evasion into broad categories of control over T cell localization, antigen recognition, and acquisition of optimal effector function. We discuss the redundancy in the pathways involved and identify knowledge gaps that must be overcome to better target immune evasion, including the need for better, routinely available tools that incorporate the growing understanding of evasion mechanisms to stratify patients for therapy and trials.
Competing Interests: Declaration of interests E.G. has received consultant fees from Achilles Therapeutics. S.A.Q. is funded by a Cancer Research UK (CRUK) Senior Cancer Research Fellowship (C36463/A22246) and a CRUK Biotherapeutic Program grant (C36463/A20764) and receives support from the CRUK-UCL Centre (C416/A18088), Cancer Research UK City of London Centre Award (C7893/A26233), and the Cancer Immuno-therapy Accelerator Award (CITA-CRUK) (C33499/A20265). C.S. acknowledges grant support from AstraZeneca, Boehringer-Ingelheim, Bristol Myers Squibb, Pfizer, Roche-Ventana, Invitae (previously Archer Dx Inc.—collaboration in minimal residual disease sequencing technologies), Ono Pharmaceutical, and Personalis. He is an AstraZeneca Advisory Board member and Chief Investigator for the AZ MeRmaiD 1 and 2 clinical trials and is also co-chief investigator of the NHS Galleri trial funded by GRAIL and a paid member of GRAIL’s Scientific Advisory Board. He receives consultant fees from Achilles Therapeutics (also a SAB member), Bicycle Therapeutics (also a SAB member), Genentech, Medicxi, China Innovation Center of Roche (CICoR), formerly Roche Innovation Center, Shanghai, Metabomed (until July 2022), and the Sarah Cannon Research Institute. C.S. has received honoraria from Amgen, AstraZeneca, Pfizer, Novartis, GlaxoSmithKline, MSD, Bristol Myers Squibb, Illumina, and Roche-Ventana. C.S. had stock options in Apogen Biotechnologies and GRAIL until June 2021 and currently has stock options in Epic Bioscience, Bicycle Therapeutics, and has stock options and is co-founder of Achilles Therapeutics. C.S. is an inventor on a European patent application relating to assay technology to detect tumor recurrence (PCT/GB2017/053289); the patent has been licensed to commercial entities and under his terms of employment. C.S. is due a revenue share of any revenue generated from such license(s). C.S. holds patents relating to targeting neoantigens (PCT/EP2016/059401), identifying patient response to immune checkpoint blockade (PCT/EP2016/071471), determining HLA LOH (PCT/GB2018/052004), predicting survival rates of patients with cancer (PCT/GB2020/050221), identifying patients who respond to cancer treatment (PCT/GB2018/051912), a US patent relating to detecting tumor mutations (PCT/US2017/28013), methods for lung cancer detection (US20190106751A1), and both a European and US patent related to identifying insertion/deletion mutation targets (PCT/GB2018/051892) and is co-inventor to a patent application to determine methods and systems for tumor monitoring (PCT/EP2022/077987). S.A.Q. is co-founder, C.S.O., and holds stock options in Achilles Therapeutics. S.A.Q. is also an inventor in patents describing the use of anti-CD25 antibodies to target Tregs and receives milestones related to these patents.
(Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)