Browsing by Author "Zilliox, Michael J."

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    Identification of human CD4+ T cell populations with distinct antitumor activity
    (American Association for the Advancement of Science, 2020-07-01) Nelson, Michelle H.; Knochelmann, Hannah M.; Bailey, Stefanie R.; Huff, Logan W.; Bowers, Jacob S.; Majchrzak-Kuligowska, Kinga; Wyatt, Megan M.; Rubinstein, Mark P.; Mehrotra, Shikhar; Nishimura, Michael I.; Armeson, Kent E.; Giresi, Paul G.; Zilliox, Michael J.; Broxmeyer, Hal E.; Paulos, Chrystal M.; Microbiology and Immunology, School of Medicine
    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.