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

Michelle H. Nelson, Hannah M. Knochelmann, Stefanie R. Bailey, Logan W. Huff, Jacob S. Bowers, Kinga Majchrzak-Kuligowska, Megan M. Wyatt, Mark P. Rubinstein, Shikhar Mehrotra, Michael I. Nishimura, Kent E. Armeson, Paul G. Giresi, Michael J. Zilliox, Hal E. Broxmeyer, Chrystal M. Paulos

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article numbereaba7443
JournalScience advances
Volume6
Issue number27
DOIs
StatePublished - Jul 2020

ASJC Scopus subject areas

  • General

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    Nelson, M. H., Knochelmann, H. M., Bailey, S. R., Huff, L. W., Bowers, J. S., Majchrzak-Kuligowska, K., Wyatt, M. M., Rubinstein, M. P., Mehrotra, S., Nishimura, M. I., Armeson, K. E., Giresi, P. G., Zilliox, M. J., Broxmeyer, H. E., & Paulos, C. M. (2020). Identification of human CD4+T cell populations with distinct antitumor activity. Science advances, 6(27), [eaba7443]. https://doi.org/10.1126/sciadv.aba7443