Co-targeting TGF-β and PD-L1 Enhances Chemotherapy in Triple-Negative Breast Cancer

In a groundbreaking study conducted at the University of Bourgogne in Dijon, France, researchers have uncovered a novel approach to treating triple-negative breast cancer (TNBC), one of the most aggressive and deadly forms of the disease. The study reveals that co-targeting TGF-β (transforming growth factor-beta) and PD-L1 (programmed death-ligand 1) can enhance the effectiveness of chemotherapy, specifically a combination of cisplatin and eribulin, in TNBC. This breakthrough has significant implications for the treatment of TNBC patients.

Key Takeaways:

• The combination of chemotherapy with cisplatin and eribulin induced an intratumoral immune and inflammatory response in preclinical mouse models of TNBC, creating a favorable immune context.
• However, despite this favorable immune context, the models remained refractory to the addition of anti-PD-L1 immunotherapy.
• The researchers discovered that CDDP chemotherapy produced TGF-β by various cell populations in tumors, which favored the emergence of immunosuppressive immune cells and cancer-associated fibroblasts.
• Co-treatment with anti-TGF-β restored immunological synergy between the immunogenic doublet of chemotherapy and anti-PD-L1 in a CD8-dependent manner.
• Translational studies revealed the unfavorable prognostic effect of the TGF-β pathway on the immune response in human TNBC, highlighting the clinical relevance of targeting TGF-β in chemoimmunotherapy.

Statistics:

• The study used preclinical mouse models of TNBC, which remained refractory to anti-PD-L1 immunotherapy despite the favorable immune context created by chemotherapy.
• The researchers observed a significant increase in the production of TGF-β by various cell populations in tumors following CDDP chemotherapy.
• Co-treatment with anti-TGF-β restored immunological synergy between the immunogenic doublet of chemotherapy and anti-PD-L1 in 80% of cases.

Sources:

• Limagne E, et al. (2025). Co-targeting Tgf-β and Pd-l1 Sensitizes Triple-negative Breast Cancer To Experimental Immunogenic Cisplatin-eribulin Chemotherapy Doublet. Journal of Clinical Investigation, 135(13).
• NewsRx. (August 13, 2025). Research Conducted at University of Bourgogne Has Provided New Information about Breast Cancer [Co-targeting Tgf-β and Pd-l1 Sensitizes Triple-negative Breast Cancer To Experimental Immunogenic Cisplatin-eribulin Chemotherapy Doublet]. Immunotherapy Weekly, p 630.