Summary: 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.
Previous studies revealed altered functional connections in problematic smartphone use (PSU), but most of the studies used self-reported data to assess PSU. Therefore, in the current study, we investigated neuroplastic changes in functional connectivity (FC) associated with PSU and objectively measured smartphone screen time (OMST) using data-driven multivariate pattern analysis. Based on our results, OMST had no direct effect on FC, but the FC between the somatomotor and the frontoparietal networks was negatively, while the connection between the somatomotor and limbic networks was positively associated with PSU. In addition, the FC between the default mode network and the limbic system was negatively, while connectivity between the default mode and the somatomotor networks was also negatively associated with PSU. In light of our findings, PSU may impair higher level brain networks, although future studies are highly needed to determine which specific objectively measured screen time activities might affect brain functions.
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.
Several studies have reported that low-dose of programmed cell death-1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors is effective. However, it is unknown whether the efficacy of low dose is as effective as standard dose. We compared the efficacy of PD-1/PD-L1 inhibitor at different doses as a single agent for patients with solid tumors. We searched published clinical trials with the clinical outcomes of PD-1/PD-L1 inhibitor until December 1, 2024. The low dose is defined as lower than the dose approved by FDA. A total of 1,084 patients from 14 studies were included in the analysis. The pooled analysis of seven studies demonstrated no significant difference in overall survival (OS) between the low dose and standard dose of PD-1/PD-L1 inhibitor. Safety evaluations from five studies indicated no significant differences in adverse events (AEs). Our study indicated that low dose of PD-1/PD-L1 inhibitor as monotherapy can provide comparable efficacy and safety to standard dose in patients with solid tumors.
