Evaluating the role of CD4+ T cells in antitumor immunity, Kagamu et al. simultaneously analyzed the naive-to-effector state change, Th polarization, and TCR clonotypes in CD4+ T cells from peripheral blood (PB), and identified Th7R – a CD4+ T cell metacluster within CD62LlowCD4+ cells that consisted of CXCR3+CCR4-CCR6+ (Th1/17) and CXCR3-CCR4-CCR6+ (CCR6 SP) CD4+ T cells, highly expressed IL-7R and TCF7, and contained clonally expanded T cells associated with PD-1 blockade efficacy. Th7R correlated with tumor infiltration by CD4+ T cells. In patients with lung cancer, maintenance of Th7R populations following PD-1 blockade predicted PFS and OS.
Contributed by Lauren Hitchings
ABSTRACT: CD4+ T-cell immunity helps clonal proliferation, migration, and cancer cell killing activity of CD8+ T cells and is essential in antitumor immune responses. To identify CD4+ T cell clusters responsible for antitumor immunity, we simultaneously analyzed the nave-effector state, Th polarization, and T cell receptor (TCR) clonotype based on single-cell RNA sequencing data. Unsupervised clustering analysis uncovered the presence of a new CD4+ T cell metacluster in the CD62Llow CD4+ T cell subpopulation, which contained multicellular clonotypes associated with efficacy of programmed death-ligand 1 (PD-1) blockade therapy. The CD4+ T-cell metacluster consisted of CXCR3+CCR4-CCR6+ and CXCR3-CCR4-CCR6+ cells and was characterized by high expression of IL-7 receptor and TCF7. The frequency of these cells in the peripheral blood significantly correlated with progression-free survival (PFS) and overall survival (OS) of lung cancer patients after PD-1 blockade therapy. In addition, the CD4+ metacluster in the peripheral blood correlated with CD4+ T-cell infiltration in the tumor microenvironment, whereas peripheral Th1 correlated with local CD8+ T-cell infiltration. Together, these findings suggest that CD62Llow CCR4-CCR6+ CD4+ T cells form a novel metacluster with predictive potential of the immune status and sensitivity to PD-1 blockade, which may pave the way for personalized antitumor immunotherapy strategies for patients.
Author Info: (1) Saitama Medical University International Medical Center, Hidaka city, Japan. (2) Saitama Medical University International Medical Center, Hidaka, Saitama, Japan. (3) The Cancer
Author Info: (1) Saitama Medical University International Medical Center, Hidaka city, Japan. (2) Saitama Medical University International Medical Center, Hidaka, Saitama, Japan. (3) The Cancer Institute Hospital of JFCR, Koto-ku, Tokyo, Japan. (4) Saitama Medical University International Medical Center, Hidaka city, Japan. (5) Saitama Medical University International Medical Center, Hidaka city, Saitama-ken, Japan. (6) Saitama Medical University International Medical Center, Hidaka city, Japan. (7) Saitama Medical University International Medical Center, Hidaka city, Japan. (8) Saitama Medical University International Medical Center, Hidaka city, Japan. (9) Saitama Medical University International Medical Center, Hidaka city, Japan. (10) Saitama Medical University International Medical Center, Hidaka city, Saitama, Japan. (11) Gunma University Graduate School of Medicine, Gunma, Japan. (12) Saitama Medical University International Medical Center, Hidaka city, Japan. (13) Keio University School of Medicine, Tokyo, Japan. (14) National Cancer Center Research Institute, Tokyo, Japan. (15) National Institute of Advanced Industrial Science and Technology, Tokyo, Japan.
