Work

CXCR5 regulates CD8+/GZMB+ T cell infiltration and apoptotic signaling in breast cancer

Year: 2026

Type: article

Abstract: Emerging evidence associates CXCR5 expression with immunotherapy outcomes; however, the intrinsic role of tumor-derived CXCR5 in modulating chemo-immunotherapy sensitivity in triple-negative breast cancer (TNBC) remains uncharacterized. This study was conducted using murine 4T1 and human MDA-MB-231 TNBC models. Tumor cell CXCR5 expression was manipulated through overexpression or shRNA-mediated silencing. Therapeutic efficacy of paclitaxel (PTX, 10 mg/kg)±Tislelizumab (TIS, 10 mg/kg) was evaluated using in vivo tumor models and T cell cytotoxicity assays. We demonstrated that combination therapy effectively suppressed 4T1 tumor growth, extended survival, and enhanced intratumoral CD8 + /GZMB + T cell infiltration coupled with increased cleaved-caspase-3 activation in murine studies. In vitro analyses revealed that CXCR5-high MDA-MB-231 cells exhibited heightened sensitivity to T-cell-mediated cytotoxicity in combination with PTX+TIS, corresponding with decreased BCL2 expression and elevated BAX levels. Our findings establish tumor-intrinsic CXCR5 as a pivotal determinant of chemo-immunotherapy efficacy in TNBC, mechanistically linked to enhanced CD8 + T cell infiltration and apoptotic signaling.

Source: iScience

DOI: 10.1016/j.isci.2026.117874