PDPN and breast cancer: 130). CAFs up-regulate tryptophan TDO2 expression, leading to enhanced secretion of Kyn. Kyn produced by CAFs can upregulate AhR expression and activate AhR-AKT-STAT3, which causes tumour cell proliferation (Ref. 131). PDPN+ CAFs (podoplanin-positive CAFs) promote resistance of HER2-positive breast cancer to trastuzumab by secreting immunosuppressive factors IDO1 and TDO2 (Ref. 132).