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

Golnaz Morad ¹, Beth A Helmink ², Padmanee Sharma ³, Jennifer A Wargo ⁴

Affiliations

¹ Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
² Department of Surgery, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
³ Department of Genitourinary Medical Oncology and Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁴ Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: jwargo@mdanderson.org.

PMID: 34624224
242 References
18 citations

Abstract

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.

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