PT - JOURNAL ARTICLE AU - Kagamu, Hiroshi AU - Kitano, Shigehisa AU - Yamaguchi, Ou AU - Yoshimura, Kenichi AU - Horimoto, Katsuhisa AU - Kitazawa, Masashi AU - Fukui, Kazuhiko AU - Shiono, Ayako AU - Mouri, Atsuhito AU - Nishihara, Fuyumi AU - Miura, Yu AU - Hashimoto, Kosuke AU - Murayama, Yoshitake AU - Kaira, Kyoichi AU - Kobayashi, Kunihiko TI - CD4<sup>+</sup> T-cell Immunity in the Peripheral Blood Correlates with Response to Anti-PD-1 Therapy AID - 10.1158/2326-6066.CIR-19-0574 DP - 2020 Mar 01 TA - Cancer Immunology Research PG - 334--344 VI - 8 IP - 3 4099 - http://cancerimmunolres.aacrjournals.org/content/8/3/334.short 4100 - http://cancerimmunolres.aacrjournals.org/content/8/3/334.full SO - Cancer Immunol Res2020 Mar 01; 8 AB - 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 patients with non–small lung cancer and found that responders had significantly (P &lt; 0.0001) higher percentages of effector, CD62Llow CD4+ T cells prior to PD-1 blockade. Conversely, the percentage of CD25+FOXP3+ CD4+ T cells was significantly (P = 0.034) higher in nonresponders. 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 nonresponders. 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+ T cells (P = 0.0015). Gene expression analysis revealed that CCL19, CLEC-2A, IFNA, IL7, TGFBR3, CXCR3, and HDAC9 were preferentially expressed in CD62Llow CD4+ T cells derived from responders. Notably, long-term responders, who had &gt;500-day progression-free survival, 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.