T-cell CX3CR1 expression as a dynamic blood-based biomarker of response to immune checkpoint inhibitors

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 and Fumito Ito ()
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Takayoshi Yamauchi: Center for Immunotherapy, Roswell Park Comprehensive Cancer Center
Toshifumi Hoki: Center for Immunotherapy, Roswell Park Comprehensive Cancer Center
Takaaki Oba: Center for Immunotherapy, Roswell Park Comprehensive Cancer Center
Vaibhav Jain: Center for Immunotherapy, Roswell Park Comprehensive Cancer Center
Hongbin Chen: Department of Medicine, Roswell Park Comprehensive Cancer Center
Kristopher Attwood: Department of Biostatistics, Roswell Park Comprehensive Cancer Center
Sebastiano Battaglia: Center for Immunotherapy, Roswell Park Comprehensive Cancer Center
Saby George: Department of Medicine, Roswell Park Comprehensive Cancer Center
Gurkamal Chatta: Department of Medicine, Roswell Park Comprehensive Cancer Center
Igor Puzanov: Department of Medicine, Roswell Park Comprehensive Cancer Center
Carl Morrison: Department of Pathology, Roswell Park Comprehensive Cancer Center
Kunle Odunsi: Center for Immunotherapy, Roswell Park Comprehensive Cancer Center
Brahm H. Segal: Department of Medicine, Roswell Park Comprehensive Cancer Center
Grace K. Dy: Department of Medicine, Roswell Park Comprehensive Cancer Center
Marc S. Ernstoff: Department of Medicine, Roswell Park Comprehensive Cancer Center
Fumito Ito: Center for Immunotherapy, Roswell Park Comprehensive Cancer Center

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: 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 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.

Date: 2021
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DOI: 10.1038/s41467-021-21619-0

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