RT Journal Article SR Electronic T1 Identification of human CD4+ T cell populations with distinct antitumor activity JF bioRxiv FD Cold Spring Harbor Laboratory SP 2019.12.31.891317 DO 10.1101/2019.12.31.891317 A1 Michelle H. Nelson A1 Hannah M. Knochelmann A1 Stefanie R. Bailey A1 Logan W. Huff A1 Jacob S. Bowers A1 Kinga Majchrzak A1 Megan M. Wyatt A1 Mark P. Rubinstein A1 Shikhar Mehrotra A1 Michael I. Nishimura A1 Kent E. Armeson A1 Paul G. Giresi A1 Michael J. Zilliox A1 Hal E. Broxmeyer A1 Chrystal M. Paulos YR 2020 UL http://biorxiv.org/content/early/2020/01/02/2019.12.31.891317.abstract AB How naturally arising human CD4+ T helper subsets impact tumor immunity is unknown. We reported that human CD4+CD26high T cells elicit potent immunity against solid tumor malignancies. As CD26high T cells secrete type-17 cytokines and have been categorized as Th17 cells, we posited these helper populations would possess similar molecular properties. Herein, we reveal that CD26high T cells are epigenetically and transcriptionally distinct from Th17 cells. Of clinical significance, CD26high T cells engineered with a chimeric antigen receptor (CAR) ablated large human tumors to a greater extent than enriched Th17, Th1, or Th2 cells. Moreover, CD26high T cells mediated curative responses in mice, even when redirected with a suboptimal CAR and without the aid of CD8+ CAR T cells. CD26high T cells co-secreted effector cytokines at heightened levels and robustly persisted. Collectively, our work reveals the potential of human CD4+ T cell populations to improve durability of solid tumor therapies.