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Role of CXCR3 signaling in response to anti-PD-1 therapy

Han, X., Wang, Y., Sun, J. et al.

Background
Tumor mutations and tumor microenvironment are associated with resistance to cancer immunotherapies. However, peripheral T cell in effective anti-programmed death 1 (PD-1) antibody treatment is poorly understood.

Methods
Mass spectrometry and conventional flow cytometry were used to investigate peripheral blood cells isolated from patients. Furthermore, melanoma mouse model was performed to assess the role of CXCR3 signaling in anti-PD-1 antibody treatment.

Findings
We revealed a marked increase in the percentage of CXCR3+ T cells in the blood of cancer patients after the first pembrolizumab infusion. This percentage decreased after the second infusion in responsive patients, whereas a sustained high percentage of CXCR3+ T cells was observed in patients with progressive disease. A low percentage of CXCR3+ T cells presented in patients with stable disease or a partial response was confirmed by conventional flow cytometry. Intriguingly, blockade of CXCR3 signaling exacerbated tumor growth in mice. Intratumoral injection with recombinant CXCL9/10 plus intraperitoneal injection of anti-PD1 antibody inhibited the tumor growth in mice.

Interpretation
The dynamic changes in CXCR3+ T cells in blood may be a prognostic factor in anti-PD-1 immunotherapy, and promotion of CXCR3-mediated signaling may be beneficial to the anti-PD-1 therapy.

Citation

Han, X., Wang, Y., Sun, J. et al. "Role of CXCR3 signaling in response to anti-PD-1 therapy" EBioMedicine (2019): 30,589–594.