Single-Cell Analysis Reveals a CD4+T-cell Cluster That Correlates with PD-1 Blockade Efficacy

Hiroshi Kagamu, Satoshi Yamasaki, Shigehisa Kitano, Ou Yamaguchi, Atsuto Mouri, Ayako Shiono, Fuyumi Nishihara, Yu Miura, Kosuke Hashimoto, Hisao Imai, Kyoichi Kaira, Kunihiko Kobayashi, Yae Kanai, Tatsuhiro Shibata, Katsuhisa Horimoto

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


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 naïve-effector state, Th polarization, and T-cell receptor 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 IL7 receptor and TCF7. The frequency of these cells in the peripheral blood significantly correlated with progression-free survival and overall survival of patients with lung cancer 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.

Original languageEnglish
Pages (from-to)4641-4653
Number of pages13
JournalCancer Research
Issue number24
Publication statusPublished - 2022 Dec 1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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