Identification of human CD4+ T cell populations with distinct antitumor activity

Sci Adv. 2020 Jul 1;6(27):eaba7443. doi: 10.1126/sciadv.aba7443. Print 2020 Jul.

Abstract

How naturally arising human CD4+ T helper subsets affect cancer immunotherapy is unclear. We reported that human CD4+CD26high T cells elicit potent immunity against solid tumors. As CD26high T cells are often categorized as TH17 cells for their IL-17 production and high CD26 expression, we posited these populations would have similar molecular properties. Here, we reveal that CD26high T cells are epigenetically and transcriptionally distinct from TH17 cells. Of clinical importance, CD26high and TH17 cells engineered with a chimeric antigen receptor (CAR) regressed large human tumors to a greater extent than enriched TH1 or TH2 cells. Only human CD26high T cells mediated curative responses, even when redirected with a suboptimal CAR and without aid by CD8+ CAR T cells. CD26high T cells cosecreted effector cytokines, produced cytotoxic molecules, and persisted long term. Collectively, our work underscores the promise of CD4+ T cell populations to improve durability of solid tumor therapies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • CD4-Positive T-Lymphocytes
  • Dipeptidyl Peptidase 4 / metabolism
  • Humans
  • Neoplasms* / pathology
  • Receptors, Chimeric Antigen*
  • T-Lymphocytes / metabolism

Substances

  • Receptors, Chimeric Antigen
  • Dipeptidyl Peptidase 4