Targeting TMED4 enhances CD8+ T cell function and CAR T cell efficacy in solid tumors through the IRE1α-autophagy axis - PubMed
2 hours ago
- #TMED4
- #solid tumors
- #CAR T cells
- TMED4 deletion in T cells boosts CD8+ T cell proliferation, tumor infiltration, and killing capacity while reducing terminal exhaustion.
- Tmed4 deficiency hyperactivates the IRE1α-XBP1 axis and induces autophagy flux, which are crucial for enhanced antitumor immunity.
- Deletion of Ern1 (IRE1α) or Becn1 (Beclin1) impairs antitumor effects, highlighting the role of ERS and autophagy.
- Tmed4-deficient CAR T cells show improved antitumor immunity, and pharmacological inhibition of TMED4 enhances tumor control.
- TMED4 is identified as a key immunotherapeutic target for improving CAR T cell efficacy in solid tumors.