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

Golnaz Morad, Beth A. Helmink, Padmanee Sharma, Jennifer A. Wargo

Research output: Contribution to journalReview articlepeer-review

500 Scopus citations


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 ICB response and toxicity are critically needed. Our understanding of the impact 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.

Original languageEnglish
Pages (from-to)5309-5337
Number of pages29
Issue number21
StatePublished - Oct 14 2021


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