RT Journal Article
SR Electronic
T1 CD4<sup>+</sup> T-cell Immunity in the Peripheral Blood Correlates with Response to Anti-PD-1 Therapy
JF Cancer Immunology Research
JO Cancer Immunol Res
FD American Association for Cancer Research
SP 334
OP 344
DO 10.1158/2326-6066.CIR-19-0574
VO 8
IS 3
A1 Kagamu, Hiroshi
A1 Kitano, Shigehisa
A1 Yamaguchi, Ou
A1 Yoshimura, Kenichi
A1 Horimoto, Katsuhisa
A1 Kitazawa, Masashi
A1 Fukui, Kazuhiko
A1 Shiono, Ayako
A1 Mouri, Atsuhito
A1 Nishihara, Fuyumi
A1 Miura, Yu
A1 Hashimoto, Kosuke
A1 Murayama, Yoshitake
A1 Kaira, Kyoichi
A1 Kobayashi, Kunihiko
YR 2020
UL http://cancerimmunolres.aacrjournals.org/content/8/3/334.abstract
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.