Enhancing TNBC Chemo-immunotherapy via combination reprogramming tumor immune microenvironment with Immunogenic Cell Death

Tumor-associated fibroblasts (TAFs) play an important role in tumor progression and therapeutic response, especially in the immunosuppressive tumor microenvironment (TME). To remodel immunosuppressive TME of 4T1 tumor, we developed a nano liposome to deliver silybin (SLN, an anti-liver fibrosis Chinese Traditional Medicine). Liposomal silybin (SLN/LIP) possessed a spherical shape with particle sizes of 75.2 nm, high stability, and good accumulation in the tumor site. After treated with SLN/LIP, alpha-SMA positive TAFs and the deposition of stroma were decreased significantly. SLN/LIP also changed the tumor immune microenvironment through the increase of IFN-gamma and IL-12, as well as reduced of TGF-beta, SDF-1, IL6 and TNF-alpha. Importantly, SLN/LIP enhanced the infiltration of cytotoxic T cells (CTLs) and transformed a cold tumor into a hot tumor. To achieve the higher antitumor efficacy, an immunogenic cell death (ICD) inducer, liposomal doxorubicin (DOX/LIP) was combined with SLN/LIP. The combination treatment led to trigger immunogenic tumor apoptosis, and enhance antitumor immunity, therefore, improved anti-tumor efficiency, and further prolonged survival duration. The combination of liposomal silybin and liposomal doxorubicin might be a new chemo-immunotherapy approach for triple negative breast cancer (TNBC) tumor treatment.

Automated summary

Tumor-associated fibroblasts play a crucial role in tumor progression and response to therapy in the immunosuppressive tumor microenvironment. By delivering silybin using nano liposomes, the study successfully altered the tumor immune microenvironment and enhanced the anti-tumor immune response. Combining an immunogenic cell death inducer, liposomal doxorubicin, further improved treatment efficacy and prolonged survival duration.