Albumin-bound paclitaxel drives a cytotoxic CD8(+) T cell enriched immune microenvironment in triple negative breast cancer.

BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by high metastatic potential and resistance to conventional therapies, representing a significant clinical challenge. Although nano albumin-bound paclitaxel (nab-PTX) has demonstrated generally good treatment effect, the mechanisms underlying its enhanced therapeutic performance, particularly its potential immunomodulatory effects, remain unclear. METHODS: Using both in vitro and in vivo TNBC models, we investigated the immunomodulatory effects of nab-PTX. Specifically, we evaluated its ability to induce immunogenic cell death (ICD), activate dendritic cells (DCs) via the cGAS-STING signaling pathway, and influence CD8(+) T cell recruitment and infiltration within the tumor microenvironment. RESULTS: Treatment with nab-PTX induced ICD in TNBC cells was associated with enhanced activation of DCs through the cGAS-STING pathway. This activation was accompanied by improved antigen presentation and a significant increase in intratumoral CD8(+) T cell infiltration. Collectively, these immune alterations suggest that nab-PTX contributes to a more immunologically active tumor microenvironment, characterized by heightened T cell mediated immune engagement. CONCLUSION: Our study indicate that, beyond its direct cytotoxic effects, nab-PTX may exert anti-tumor activity in TNBC through modulation of the tumor immune microenvironment. By inducing ICD and promoting DCs activation, nab-PTX appears to support CD8(+) T cell recruitment, thereby potentially enhancing immune mediated tumor regression. This immunologically supportive role of nab-PTX highlights its potential value in strategies aimed at improving the efficacy of chemotherapy based or immunotherapy combined treatments in TNBC.