Moxibustion Promotes Tumor Immune Responses and Vascular Normalization to Enhance Antitumor Effect of Cisplatin in Lewis Lung Carcinoma Mice.

The immunosuppressive tumor microenvironment and vascular abnormalities are important factors affecting the anticancer effects of chemotherapeutic drugs. Previous studies have shown that moxibustion combined with cisplatin can improve tumor immunity and vascular normalization. The aim is to further explore the pathways and molecular mechanisms by which moxibustion combined with cisplatin exerts anti-tumor effects through regulating the tumor immune-vascular microenvironment. Through RNA sequencing and bioinformatics analysis, we identified related signaling pathways and key molecules, which were subsequently validated at both cellular and molecular levels. The combination of moxibustion and cisplatin enhanced the infiltration of CD4+ T cells and myeloid dendritic cells in tumor tissues. Moreover, it elevated the M1/M2 and Th1/Th2 ratios along with enhanced Th1 cell polarization. This therapeutic approach modulated immune-related molecules through upregulation of Il2 and downregulation of Il1β at the mRNA level, accompanied by decreased protein expression of CXCL1, IL-13, CCL3, and CCL4. Furthermore, moxibustion upregulated Ifnγ and Pf4 mRNA levels and downregulated Vegfa and Flt1. Thus, the imbalance between pro-angiogenic and anti-angiogenic factors in the tumor microenvironment can be corrected. Notably, the anti-tumor effects of moxibustion combined with cisplatin were abrogated upon intratumoral injection of the IFN-γ neutralizing antibody, suggesting the critical role of IFN-γ. The findings demonstrate that the combination of moxibustion and cisplatin can enhance tumor immunity, inhibit tumor angiogenesis. This therapeutic effect is potentially mediated through the upregulation of IFN-γ.