Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 109, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2022.108799
Keywords
IL-28B; Colorectal cancer; M2 macrophage; Cancer immunotherapy; Anti-tumor
Categories
Funding
- National Natural Science Foundation of China [81874169, 81801557, 82171810]
- Shandong Provincial Natural Science Foundation [ZR2020KH033]
- Chinese and Foreign Cooperation Cultivation Project of Jining Medical University
- NSFC Cultivation Project of Jining Medical University [JYP2018KJ22]
- Doctoral Startup Fund of Jining Medical University [JY2016QD030]
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IL-28B inhibits colon cancer progression by downregulating tumor-associated macrophages, rather than directly promoting apoptosis or inhibiting cell proliferation. It halts M2 macrophage polarization and differentiation via inhibition of the STAT3 and JNK signaling pathways.
The type III interferon family (IFN-III), including IFN-lambda 3 [interleukin (IL)-28B], has antiviral, anti-tumor, and immunomodulatory activities. Although the IL-28B anti-tumor effect has been extensively explored, its underlying mechanism remains unclear. Here, we explored IL-28B effects on colon cancer. Our results show that IL-28B significantly inhibits colon cancer progression in a mouse MC38 tumor cell colonization model and colitis-associated colorectal tumor model. Interestingly, IL-28B does not directly promote apoptosis or inhibit MC38 tumor cell proliferation in vitro. Rather, IL-28B treatment has indirect anti-tumor activity by downregulating tumor-associated macrophages. Furthermore, IL-28B inhibits M2 macrophage polarization in vitro, while also halting M2 macrophage differentiation predominantly via inhibition of the signal transducer and activator of transcription (STAT)3 and c-Jun N-terminal kinase (JNK) signaling pathways. Our findings revealed that IL-28B inhibits M2 macrophages in the tumor microenvironment to delay colon cancer progression. These findings provide novel evidence of IL-28B anti-tumor and immunomodulatory activities.
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