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CD4+ T-cell immunity in the peripheral blood correlates with response to anti-PD-1 therapy

Kagamu, H., Kitano, S., Yamaguchi, O. et al.

Accumulating evidence indicates that CD8+ T cells in the tumor microenvironment and systemic CD4+ T-cell immunity play an important role in mediating durable antitumor responses. We longitudinally examined T-cell immunity in the peripheral blood of non-small lung cancer patients and found that responders had significantly (P < 0.0001) higher percentages of effector, CD62Llow CD4+ T cells prior to PD-1 blockade. Conversely, the percentage of CD25+FOXP3+ CD4+ T cells were significantly (P = 0.034) higher in non-responders. We developed a formula, which demonstrated 85.7% sensitivity and 100% specificity, based on the percentages of CD62Llow CD4+ T cells and CD25+FOXP3+ cells to predict non-responders. Mass cytometry analysis revealed that the CD62Llow CD4+ T cell subset expressed T-bet+, CD27-, FOXP3-, and CXCR3+, indicative of a Th1 subpopulation. CD62Llow CD4+ T cells significantly correlated with effector CD8+ T cells (P = 0.0091) and with PD-1 expression on effector CD8+ (P = 0.0015). Gene expression analysis revealed that CCL19, CLEC-2A, IFNA, IL-7, TGFBR3, CXCR3 and HDAC9 were preferentially expressed in CD62Llow CD4+ T cells derived from responders. Notably, long-term responders, who had >500 day PFS, showed significantly higher numbers of CD62Llow CD4+ T cells prior to PD-1 blockade therapy. Decreased CD62Llow CD4+ T-cell percentages after therapy resulted in acquired resistance, with long-term survivors maintaining high CD62Llow CD4+ T-cell percentages. These results pave the way for new treatment strategies for patients, by monitoring CD4+ T cell immune statuses in their peripheral blood.

Citation

Kagamu, H., Kitano, S., Yamaguchi, O. et al. "CD4+ T-cell immunity in the peripheral blood correlates with response to anti-PD-1 therapy" Cancer Immunology Research (2019): 334–44