PGE2 limits effector expansion of tumour-infiltrating stem-like CD8+ T cells

Abstract Cancer-specific TCF1 + stem-like CD8 + T cells can drive protective anticancer immunity through expansion and effector cell differentiation 1–4 ; however, this response is dysfunctional in tumours. Current cancer immunotherapies 2,5–9 can promote anticancer responses through TCF1 + stem-like CD8 + T cells in some but not all patients. This variation points towards currently ill-defined mechanisms that limit TCF1 + CD8 + T cell-mediated anticancer immunity. Here we demonstrate that tumour-derived prostaglandin E2 (PGE 2 ) restricts the proliferative expansion and effector differentiation of TCF1 + CD8 + T cells within tumours, which promotes cancer immune escape. PGE 2 does not affect the priming of…

• DF
  Deutsche Forschungsgemeinschaft

  Awards: 452881907, SFB 1371, SFB-TRR 338/1 2021-452881907, SFB-TRR 338/1, KO5055-2-1, ZE 832/8-1, 449174900, 461704785, 338/1 2021-452881907, SFB-TRR 338, 442405234, ZE 832/6-1, 510821390, 424926990
• BF
  Bayerische Forschungsstiftung
• EK
  Else Kröner-Fresenius-Stiftung

  Award: 756017
• TU
  Technische Universität München

  Award: SFB 1371
• DK
  Deutsche Krebshilfe

  Award: 70113918
• EB
  Elitenetzwerk Bayern