Identification of human CD4 T cell populations with distinct antitumor activity. Journal Article

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Authors: Nelson, MH; Knochelmann, HM; Bailey, SR; Huff, LW; Bowers, JS; Majchrzak-Kuligowska, K; Wyatt, MM; Rubinstein, MP; Mehrotra, S; Nishimura, MI; Armeson, KE; Giresi, PG; Zilliox, MJ; Broxmeyer, HE; Paulos, CM
Article Title: Identification of human CD4 T cell populations with distinct antitumor activity.
Abstract: How naturally arising human CD4 T helper subsets affect cancer immunotherapy is unclear. We reported that human CD4CD26 T cells elicit potent immunity against solid tumors. As CD26 T cells are often categorized as T17 cells for their IL-17 production and high CD26 expression, we posited these populations would have similar molecular properties. Here, we reveal that CD26 T cells are epigenetically and transcriptionally distinct from T17 cells. Of clinical importance, CD26 and T17 cells engineered with a chimeric antigen receptor (CAR) regressed large human tumors to a greater extent than enriched T1 or T2 cells. Only human CD26 T cells mediated curative responses, even when redirected with a suboptimal CAR and without aid by CD8 CAR T cells. CD26 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.
Journal Title: Science advances
Publisher: Unknown  
Date Published: 2020