The use of DAT for immunotherapies
Challenge and innovation
Immunotherapies are crucial for cancer prevention and treatment but remain limited in efficacy. Allogeneic hematopoietic stem cell transplantation (allo‑HSCT) can cure many otherwise incurable hematological cancers, yet success is constrained by severe graft‑versus‑host disease (GvHD) and the persistent difficulty of reliably predicting survival and relapse after allo‑HSCT.
The invention improves allo‑HSCT outcomes by leveraging the microbiome and its metabolites to modulate graft‑versus‑host disease (GvHD) while preserving graft‑versus‑leukemia (GvL) effects. Integrated analyses in allo‑HSCT patients identified a microbiome signature correlating with immuno‑modulatory metabolites (IMMs) and improved survival, summarized by the Immuno‑modulatory Metabolite Risk Index (IMM‑RI). Preclinical data show DAT promotes intestinal regeneration and balances GvL/GvHD via mTORC1‑ and STING‑dependent pathways.
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