IL-33/ST2 activation of IL-9-secreting T cells alters the balance of fatal immunity and tumor immunity (TRAN1P.926)

• DOI: 10.4049/jimmunol.194.supp.140.8
• Publication Date: 2023-01-01T10:10:56Z
• Authors: Abdulraouf Ramadan; Jilu Zhang; Brad Griesenauer; Reuben Kapur; Helmut Hanenberg; Jie Sun; Mark Kaplan; Sophie Paczesny
• Keywords: Adoptive Cell Transfer; Interleukin 33

Abstract Allogeneic hematopoietic cell transplantation (HCT) is the most potent curative therapy for cancers of bone marrow; however, graft-versus-host disease (GVHD) continues to be major limitation successful HCT, with mortality rates around 50%. Current strategies suppress GVHD also compromise beneficial graft-versus-tumor (GVT) activity. We have shown that elevated IL-33-sequestering soluble ST2 in plasma a risk factor severe GVHD. In addition, IL-9-secreting Th9 and Tc9 subsets higher antitumor activity than Th1 Tc1. hypothesized induction ST2/IL-33 pathway will both alleviate increase GVT Differentiation IL-33 increased expression membrane (ST2L) PU.1, transcription promotes IL-9 production. Adoptive transfer IL-33-treated cells marrow HCT murine models showed less compared without IL-33, or Th2 are protective Polarization total T secreting was via help. Transcriptome analysis IL-33-T9 genes anti-tumor Higher demonstrated GFP+MLL-AF9 acute myeloid leukemia. Human strong anti-leukemia cytolytic Thus, represent promising cellular following HCT.