Tumor cell-released autophagosome (TRAP) programs inflammatory CAFs to drive the immune-excluded TIME through C3a.

Tumor cell-released autophagosomes (TRAP) program inflammatory CAFs to promote immune exclusion via C3a, with a 96% accuracy in distinguishing breast cancer patients.

• Why it matters: Understanding how the tumor microenvironment becomes immune-excluded is crucial for improving immunotherapy responses, as current knowledge of upstream signals remains limited.
• What they did: Researchers combined single-cell RNA sequencing and functional validation to show that TRAP activates inflammatory CAFs, leading to C3a production through the HSP70-TLR4-MyD88-ERK/p38 pathway, affecting immune cell infiltration.
• The result: Disrupting the TRAP-iCAF-C3a/C3aR axis reprograms the tumor microenvironment, enhances anti-PD-L1 therapy, and plasma TRAP and C3a levels serve as highly accurate biomarkers for breast cancer staging.