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Human anti‐programmed death‐1 ( PD ‐1) antibody possesses the capability to revitalize host T cells and has been an effective therapy for metastatic malignant melanoma ( MM ). The precise subsets of T cells predominantly activated by anti‐ PD ‐1, however, have not yet been clarified. In this study, peripheral blood mononuclear cells obtained from  MM  patients scheduled to receive anti‐ PD ‐1 (nivolumab) therapy, and healthy subjects ( HS ), were systematically examined on flow cytometry to identify changes in the proportion of immune cell subsets. Compared with  HS ,  MM  patients prior to therapy had an increased proportion of activated  CD 8+ T cells with effector memory phenotypes (Tem), and  PD ‐1 positive subsets of  CD 4+ central memory T cells (Tcm) and T‐helper (Th)17 cells. After a single course of anti‐ PD ‐1 therapy,  MM  patients had an increase in activated Tem and Tcm subsets of  CD 4+ and  CD 8+ T cells, and activated Th1 plus T‐helper follicular 1 cells. There was no consistent change in the proportion of Tfh cells, B cells, natural killer cells, or dendritic cells. The observed activated phenotypes were attenuated during the course of therapy, but regulatory T cells belonging to the  CD 3+ CD 4+ CD 45 RO +CD25high fraction increased at disease progression. Taken together, anti‐ PD ‐1 therapy modulates systemic immune reactions and exerts anti‐tumor effects, not only by revitalizing Tem and Tcm of  CD 4+ and  CD 8+ T cells, but also via a shift to a Th1 phenotype.

cancer science

Activation of central/effector memory T cells and T‐helper 1 polarization in malignant melanoma patients treated with anti‐ programmed death ‐1 antibody