Expression of CD39 Identifies Activated Intratumoral CD8+ T Cells in Mismatch Repair Deficient Endometrial Cancer

• Main Authors: Bremer, E. (Author), de Bruyn, M. (Author), Elsinga, P.H (Author), Kol, A. (Author), Lubbers, J.M (Author), Nijman, H.W (Author), Paijens, S.T (Author), Plat, A. (Author), Spierings, D.C.J (Author), van Rooij, N. (Author), Vlaming, M.R (Author), Ważyńska, M.A (Author), Workel, H.H (Author)
• Format: Article
• Language: English
• Published: MDPI 2022
• Subjects: CD103; CD39; exhaustion; PD-1; TGF-β
• Online Access: View Fulltext in Publisher

 Identification of human cancer-reactive CD8+ T cells is crucial for the stratification of patients for immunotherapy and determination of immune-therapeutic effects. To date, these T cells have been identified mainly based on cell surface expression of programmed cell death protein 1 (PD-1) or co-expression of CD103 and CD39. A small subset of CD103− CD39+ CD8+ T cells is also present in tumors, but little is known about these T cells. Here, we report that CD103− CD39+ CD8+ T cells from mismatch repair-deficient endometrial tumors are activated and characterized predominantly by expression of TNFRSF9. In vitro, transforming growth factor-beta (TGF-β) drives the disappearance of this subset, likely through the conversion of CD103− CD39+ cells to a CD103+ phenotype. On the transcriptomic level, T cell activation and induction of CD39 was associated with a number of tissue residence and TGF-β responsive transcription factors. Altogether, our data suggest CD39+ CD103− CD8+ tumor-infiltrating T cells are recently activated and likely rapidly differentiate towards tissue residence upon exposure to TGF-β in the tumor micro-environment, explaining their relative paucity in human tumors. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.