Human Th26 cells possess a distinct inflammatory signature and mediate durable memory responses against established tumor
Michelle H. Nelson1*, Stefanie R. Bailey1, Logan W. Huff1, Jacob S. Bowers1, Kinga Majchrzak1, Krishnamurthy Thyagarajan1, Megan M. Wyatt1, Shikhar Mehrotra1, Mark P. Rubinstein1, Michael I. Nishimura2, Kent E. Armeson1, Michael J. Zilliox2, Chrystal M. Paulos1*
1Medical University of South Carolina
2 Stritch School of Medicine, Loyola University Chicago
We discovered a unique human CD4+ T cell population that expresses high surface CD26 (an enzymatic costimulatory molecule)-designated Th26 cells. Compared to Th1, Th2 or Th17 cells, Th26 cells possess a distinct inflammatory signature and are genetically distinct from classic helper T cells. These novel T cells are especially polyfunctional, simultaneously co-secreting inflammatory cytokines (IL-17A, IFN-γ and IL-22) and cytotoxic molecules (granzyme B, perforin and CD107A). Moreover, they are rich in their expression in a plethora of chemokine receptors, including CXCR3, CCR6 and CXCR6. Infused CAR+ Th26 cells regressed human tumors to a greater extent than classic Th1, Th2 or Th17 cells, leading to durable cures. Both CAR+Th17 and Th26 cells bolstered the engraftment of co-infused CAR+CD8+ T cells. Interestingly, Th26 but not Th17 cells killed tumor without help from CD8+ T cells. The therapeutic effectiveness of Th26 cells was associated with their pronounced persistence. These findings reveal that Th26 cells have implications for the design of new cancer immunotherapeutics.
MHN Funding: American Cancer Society Postdoctoral (122704-PF-13-084-01-LIB), Jeane B. Kempner Fellowships, T32 NIAMS Fellow; CMP Funding: NCI-1 R01 CA208514.