A circulating T-cell differentiation marker to predict response to immune checkpoint inhibitors

Yamauchi, T.; Hoki, T.; Oba, T.; Jain, V.; Chen, H.; Attwood, K.; Battaglia, S.; George, S.; Chatta, G.; Puzanov, I.; Morrison, C.; Odunsi, K.; Segal, B. H.; Dy, G. K.; Ernstoff, M. S.; Ito, F.

doi:10.1101/2020.06.13.095844

bioRxiv · 10.1101/2020.06.13.095844

A circulating T-cell differentiation marker to predict response to immune checkpoint inhibitors

Yamauchi, T.·Hoki, T.·Oba, T.·Jain, V.·Chen, H.·Attwood, K.·Battaglia, S.·George, S.·Chatta, G.·Puzanov, I.·Morrison, C.·Odunsi, K.·Segal, B. H.·Dy, G. K.·Ernstoff, M. S.·Ito, F.

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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 investigated a role of CX3C chemokine receptor 1 (CX3CR1), a marker of T-cell differentiation, in predicting response to ICI therapy. Successful treatment of tumor-bearing mice with ICI increased the frequency and T-cell receptor clonality of the peripheral CX3CR1+CD8+ T-cell subset that included 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 correlated with response and survival in patients with non-small cell lung cancer (NSCLC). Taken together, these data support T-cell CX3CR1 expression as a blood-based dynamic biomarker to predict response to ICI therapy.

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Yamauchi, T., Hoki, T., Oba, T., Jain, V., Chen, H., Attwood, K., Battaglia, S., George, S., Chatta, G., Puzanov, I., Morrison, C., Odunsi, K., Segal, B. H., Dy, G. K., Ernstoff, M. S., Ito, F.. 2020-06-14. A circulating T-cell differentiation marker to predict response to immune checkpoint inhibitors. https://doi.org/10.1101/2020.06.13.095844

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