Abstract
AbstractImmune checkpoint inhibitors (ICI) have revolutionized treatment for various cancers; however, durable response is limited to only a subset of patients. Discovery of blood-based biomarkers that reflect dynamic change of the tumor microenvironment, and predict response to ICI, will markedly improve current treatment regimens. Here, we investigate CX3C chemokine receptor 1 (CX3CR1), a marker of T-cell differentiation, as a predictive correlate of response to ICI therapy. Successful treatment of tumor-bearing mice with ICI increases the frequency and T-cell receptor clonality of the peripheral CX3CR1+CD8+ T-cell subset that includes an enriched repertoire of tumor-specific and tumor-infiltrating CD8+ T cells. Furthermore, an increase in the frequency of the CX3CR1+ subset in circulating CD8+ T cells early after initiation of anti-PD-1 therapy correlates with response and survival in patients with non-small cell lung cancer. Collectively, these data support T-cell CX3CR1 expression as a blood-based dynamic early on-treatment predictor of response to ICI therapy.
Funder
Astellas Foundation for Research on Metabolic Disorders
Uehara Memorial Foundation
U.S. Department of Health & Human Services | NIH | National Cancer Institute
Melanoma Research Alliance
Sarcoma Foundation of America
United States Department of Defense | United States Army | Army Medical Command | Congressionally Directed Medical Research Programs
U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
Cited by
104 articles.
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