T-cell CX3CR1 Expression As a Dynamic Blood-based Biomarker of Response to Immune Checkpoint Inhibitors

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Mar 4

PMID 33658501

Citations 77

Authors

Takayoshi Yamauchi

Toshifumi Hoki

Takaaki Oba

Vaibhav Jain

Hongbin Chen

Kristopher Attwood

Sebastiano Battaglia

Saby George

Gurkamal Chatta

Igor Puzanov

Carl Morrison

Kunle Odunsi

Brahm H Segal

Grace K Dy

Marc S Ernstoff

Fumito Ito

Affiliations

Soon will be listed here.

Abstract

Immune 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 CX3CR1CD8 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.

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