Impact of PD-L1 overexpression on immune checkpoint inhibitor efficacy in triple-negative breast cancer using a 4T1 murine model.

Bulk RNA sequencing was performed to investigate transcriptomic changes in 4T1 tumors treated with anti-PD-L1 therapy. Tumors were derived from 4T1 control and PD-L1-overexpressing cells injected into mice, followed by IgG or anti-PD-L1 treatment. Gene expression analysis revealed distinct immune-related pathway alterations, with reduced immune activation in PD-L1-overexpressing tumors. Differentially expressed genes suggested an immunosuppressive tumor microenvironment, potentially contributing to resistance to anti-PD-L1 therapy. These findings provide insights into the molecular mechanisms underlying immune checkpoint inhibitor response in triple-negative breast cancer. Syngeneic mouse models were established by injecting 1 × 10⁵ control 4T1 or PD-L1-overexpressing 4T1 cells into the mammary fat pad of BALB/c mice. Tumor-bearing mice were treated twice weekly with either IgG (150 µg/100 µL) or anti-PD-L1 inhibitor (BP0101; 150 µg/100 µL) via intraperitoneal injection. Tumor growth was monitored using digital calipers, and the study concluded after three treatment sessions (17 days in total). Tumors were harvested post-euthanasia and subjected to bulk RNA sequencing to analyze transcriptional changes associated with PD-L1 overexpression and anti-PD-L1 therapy. This study aimed to identify immune-related gene expression differences contributing to treatment response.