CXCR5 regulates CD8+/GZMB+ T cell infiltration and apoptotic signaling in breast cancer
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.
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BibTeX
@article{feng2026cxcr5,
title = {{CXCR5 regulates CD8+/GZMB+ T cell infiltration and apoptotic signaling in breast cancer}},
author = {Weihong Feng and Jin Yan and Xue Gong and Jiandong Hu and Mengli Jin and Chunhua Ma and Fenge Li},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117874},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03257-8},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - CXCR5 regulates CD8+/GZMB+ T cell infiltration and apoptotic signaling in breast cancer
AU - Weihong Feng
AU - Jin Yan
AU - Xue Gong
AU - Jiandong Hu
AU - Mengli Jin
AU - Chunhua Ma
AU - Fenge Li
PY - 2026
DA - 2026/10/21
JO - iScience
DO - 10.1016/j.isci.2026.117874
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03257-8
AB - 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.
SN - 2589-0042
ER -