CD4 + T-cell Immunity in the Peripheral Blood Correlates with Response to Anti-PD-1 Therapy

• Published in: Cancer immunology research Vol. 8; no. 3; p. 334
• Main Authors: Kagamu, Hiroshi, Kitano, Shigehisa, Yamaguchi, Ou, Yoshimura, Kenichi, Horimoto, Katsuhisa, Kitazawa, Masashi, Fukui, Kazuhiko, Shiono, Ayako, Mouri, Atsuhito, Nishihara, Fuyumi, Miura, Yu, Hashimoto, Kosuke, Murayama, Yoshitake, Kaira, Kyoichi, Kobayashi, Kunihiko
• Format: Journal Article
• Language: English
• Published: United States 01.03.2020
• ISSN: 2326-6074
• DOI: 10.1158/2326-6066.CIR-19-0574

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 ( < 0.0001) higher percentages of effector, CD62L CD4 T cells prior to PD-1 blockade. Conversely, the percentage of CD25 FOXP3 CD4 T cells was significantly ( = 0.034) higher in nonresponders. We developed a formula, which demonstrated 85.7% sensitivity and 100% specificity, based on the percentages of CD62L CD4 T cells and CD25 FOXP3 cells to predict nonresponders. Mass cytometry analysis revealed that the CD62L CD4 T-cell subset expressed T-bet , CD27 , FOXP3 , and CXCR3 , indicative of a Th1 subpopulation. CD62L CD4 T cells significantly correlated with effector CD8 T cells ( = 0.0091) and with PD-1 expression on effector CD8 T cells ( = 0.0015). Gene expression analysis revealed that , and were preferentially expressed in CD62L CD4 T cells derived from responders. Notably, long-term responders, who had >500-day progression-free survival, showed significantly higher numbers of CD62L CD4 T cells prior to PD-1 blockade therapy. Decreased CD62L CD4 T-cell percentages after therapy resulted in acquired resistance, with long-term survivors maintaining high CD62L 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.