Galectin-9 expression clinically associated with mature dendritic cells infiltration and T cell immune response in colorectal cancer

Abstract

Background Galectin-9 is a member of the galectin family and has been reported to have a tumor-promoting or antitumor effect in response to the immune microenvironment. However, the immunomodulatory effect of galectin-9 in colorectal cancer (CRC) remains unclear. The antigen presentation and antitumor immune effects of galectin-9 in CRC were examined in this study. Methods The expression of galectin-9, dendritic cell markers (CD208 and CD1a), T-cell markers (CD3 and CD8) and mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6) was assessed using immunohistochemistry in CRC samples. The correlation between galectin-9 and immune cells or immunomodulatory factors was also evaluated via multiple gene expression databases. Results The level of galectin-9 was decreased in mismatch repair-proficient patients compared with mismatch repair-deficient patients (p = 0.0335). GSEA showed that the regulatory mechanism of galectin-9 in CRC was related to a variety of immune pathways. Galectin-9 expression was strongly correlated with immune cell infiltration and immunomodulators (all p < 0.0001). In the relationship between galectin-9 expression and the infiltration of DCs, there was a negative correlation in CD1a + immature DCs (R = -0.263, p = 0.042). A strong positive correlation was observed in CD208 + mature DCs (R = 0.391, p < 0.01). Patients with high galectin-9 expression also exhibited abundant CD8 + T-cell and CD3 + T-cell infiltration. Conclusion Collectively, our findings provide evidence that galectin-9 may increase the antitumor immune response of patients with CRC. DCs play an important role in galectin-9-mediated antitumor immune responses, which provides further insight into the development of immunotherapy.

The Dual Role of the NFATc2/galectin‐9 Axis in Modulating Tumor‐Initiating Cell Phenotypes and Immune Suppression in Lung Adenocarcinoma

“…anti-tumor immunity of colorectal cancer. [45] However, the role of galectin-9 in cancer immune may vary amongst different cancer types. Whether galectin-9 could regulate DC function in lung cancer remains unclear.…”

“…[ 44 ] A recent study in colorectal cancer reported that the expression level of galectin‐9 positively correlated with infiltration of mature DCs and increased infiltration of CD8 + T cells, indicating the supportive role of galectin‐9 in anti‐tumor immunity of colorectal cancer. [ 45 ] However, the role of galectin‐9 in cancer immune may vary amongst different cancer types. Whether galectin‐9 could regulate DC function in lung cancer remains unclear.…”