Hallmarks of response, resistance, and toxicity to immune checkpoint blockade

Unprecedented advances have been made in cancer treatment with the use of immune checkpoint blockade (ICB). However, responses are limited to a subset of patients, and immune-related adverse events (irAEs) can be problematic, requiring treatment discontinuation. Iterative insights into factors intrinsic and extrinsic to the host that impact ICBresponseandtoxicity are critically needed. Our understanding of theimpact of host-intrinsic factors (such as the host genome, epigenome, and immunity) has evolved substantially over the past decade, with greater insights on these factors and on tumor and immune co-evolution. Additionally, we are beginning to understand the impact of acute and cumulative exposures-both internal and external to the host (i.e., the exposome)-on host physiology and response to treatment. Together these represent the current day hallmarks of response, resistance, and toxicity to ICB. Opportunities built on these hallmarks are duly warranted.

Automated summary

This passage discusses the unprecedented advances in cancer treatment with immune checkpoint blockade (ICB), highlighting the critical need for insights into factors intrinsic and extrinsic to the host that impact ICB response and toxicity. There has been substantial progress in understanding the impact of host-intrinsic factors and the exposome on host physiology and response to treatment, representing the hallmarks of response, resistance, and toxicity to ICB in current day.