Description

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. Paulos^1*

¹Medical University of South Carolina

² Stritch School of Medicine, Loyola University Chicago

*Corresponding Author

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.