| Summary: | Galectin-9 (Gal-9) is an immune checkpoint protein that facilitates T cell exhaustion and modulates the tumor-associated microenvironment, and could be a potential target for immune checkpoint inhibition. This study was conducted to assess Gal-9 expression in triple-negative breast cancer (TNBC) and evaluate its association with programmed cell death ligand 1 (PD-L1) expression and immune cell infiltration in tumors and the clinical outcome of patients. Overall, 109 patients with TNBC were included. Gal-9 expression was assessed its relationships with tumor clinicopathologic characteristics, tumor-infiltrating lymphocyte (TIL) levels, PD-L1+ immune cells, and tumor cells by tissue microarray and immunohistochemistry. Low Gal-9 expression was statistically correlated with higher tumor stage (p = 0.031) and presence of lymphovascular invasion (<i>p</i> = 0.008). High Gal-9 expression was associated with a high level of stromal TILs (sTIL; <i>p</i> = 0.011) and positive PD-L1 expression on tumor cells (<i>p</i> = 0.004). In survival analyses, low Gal-9 expression was associated with significantly poor OS (<i>p</i> = 0.013) in patients with TNBC with PD-L1 negativity in tumor cells. Our findings suggest that increased Gal-9 expression is associated with changes in the antitumor microenvironment, such as increased immune cell infiltration and antimetastatic changes. This study emphasizes the predictive value and promising clinical applications of Gal-9 in TNBC.
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