HOXD13-mediated immune crosstalk between cancer cells and tumor-associated macrophages drives colorectal cancer progression - PubMed
5 hours ago
- #Tumor Microenvironment
- #Colorectal Cancer
- #Immunotherapy
- HOXD13 is upregulated in colorectal cancer (CRC), especially in metastatic cases, and correlates with poorer clinical outcomes.
- HOXD13 promotes an immunosuppressive tumor microenvironment (TME) by inducing M2-type polarization of tumor-associated macrophages (TAMs) and suppressing CD8+ T cell-mediated antitumor immunity.
- Mechanistically, HOXD13 transcriptionally upregulates amphiregulin (AREG) and paired immunoglobulin-like type 2 receptor alpha (PILRA) in CRC cells.
- M2-polarized TAMs release transforming growth factor beta 1 (TGF-β1), which further enhances HOXD13 expression in CRC cells via Smad2/3 signaling, creating a self-reinforcing immunosuppressive loop.
- Combined inhibition of AREG and programmed cell death ligand 1 (PD-L1) disrupts this crosstalk, restores antitumor immunity, and suppresses CRC progression.
- Targeting the HOXD13 signaling axis may represent a promising strategy to improve immunotherapy responses in CRC.