CXCL1 promotes immune escape in colorectal cancer by autophagy-mediated MHC-I degradation

Background: Immunotherapy is now seen as a potential remedy for colorectal Cancer (CRC). Chemokines play a crucial role in tumors, including CRC, which contains CXCL1. We attempted to study how CXCL1 impacts immune escape in CRC.

Methods: Bioinformatics analysis was used to examine CXCL1 level in CRC. qRT-PCR was used to assess CXCL1 and MHC-I (HLA-A, B, C) levels. Cell Counting Kit-8 (CCK-8) was used to measure cell viability. Cytotoxicity assay kit was utilized to assay CD8⁺ T cell cytotoxicity against CRC. Flow cytometry tested proliferation and Apoptosis of CD8⁺ T cells. Chemotaxis assay evaluated chemotaxis of CD8⁺ T cells towards CRC. Immunofluorescence examined expression of Autophagy marker LC3 and localization of NBR1/MHC-I. Western blot analysis measured protein levels of chemokines CXCL9 and CXCL10, autophagy-related proteins LC3-I and LC3-II, and MHC-I (HLA-A, B, C).

Results: Bioinformatics analysis and qRT-PCR presented that CXCL1 was upregulated in CRC. Cell experiments demonstrated that CXCL1 overexpression promoted immune escape in CRC. Rescue experiments revealed that the Autophagy inducer Rapa could attenuate the inhibitory effect of CXCL1 low expression on immune escape in CRC. Further studies showed that CXCL1 promoted immune escape in CRC by autophagy-mediated MHC-I degradation.

Conclusion: CXCL1 promoted immune escape in CRC by autophagy-mediated MHC-I degradation, suggesting that CXCL1 may be a possible immunotherapeutic target for CRC.

Autophagy; CXCL1; Colorectal cancer; Immune escape; MHC-I.