IL28-B reprograms tumor-associated macrophages (TAM) to promote
anti-tumor effects in colon cancer
The type III interferon family (IFN-III), including IFN-λ3 (IL-28B), has
antiviral, anti-tumor, and immunomodulatory activities. Although IL-28B
anti-tumor effect has been extensively explored, its underlying
anti-tumor mechanism remains unclear. Here, we explored IL-28B effects
on colon cancer. We found that IL-28B significantly inhibited colon
cancer growth in a murine MC38 tumor cell engraftment model.
Interestingly, IL-28B did not directly promote apoptosis or inhibit MC38
tumor cell proliferation in vitro. IL-28B treatment exerted indirect
anti-tumor activity by downregulating M2 macrophages in the tumor
microenvironment. Furthermore, IL-28B inhibited M2 macrophage
polarization in vitro. It also halted M2 macrophage differentiation
predominantly via inhibition of the STAT3 and JNK signaling pathways.
Our findings revealed that IL-28B inhibited M2 macrophages in the tumor
microenvironment to delay colon cancer progression. Our study provides
new evidence of IL-28B anti-tumor and immunomodulatory activities.