CBLN2 overexpression inhibits colorectal cancer progression and improves immunotherapy responses

Cerebellin 2 (CBLN2) has critical roles in regulating neuronal function, however, its functions in cancer are poorly studied. In our project, we found that CBLN2 expression is significantly downregulated in colorectal carcinoma (CRC), which is related to poor outcomes of CRC patients. In addition, we found that CBLN2 is closely associated with immune infiltrates in CRC samples, especially CD8 + T cells. Mechanistically, we discovered that CBLN2 could inhibit STAT3-induced PD-L1 and beta-catenin activation in CRC. Further experiments revealed that CBLN2 overexpression could inhibit oncogenic properties of CRC cells in vitro and CRC tumor growth in vivo. What's more, we also confirmed that the activation of CBLN2 could improve the efficiency of immune checkpoint blockade (ICB) treatment in the MC38 CRC model. In conclusion, the CBLN2-STAT3 axis may act as a novel potential target for CRC treatment.