Doxorubicin-Isoniazid Conjugate Regulates Immune Response and Tumor Microenvironment to Enhance Cancer Therapy

Figure 1. Schematic representing the conjugate DOX-INH, a potent regulator combing ICD and immune checkpoint blockade. In tumor microenvironment, the release of free DOX stimulate immunogenic cell death (ICD), which attract immune cells into the tumor microenvironment. The activated cytotoxic T cells can further enhance its activity by auto secreting 5-HT, releasing immune stimulators (e.g., Granzyme B, IFN-γ). However, the high expression of MAOA in T cells degrades 5-HT and inhibits the activation of T cells, resulting in immunosuppression. Moreover, high expression of MAOA in tumor cells can activate a variety of signaling pathways (Shh, IL-6, and TGF-β) in the process of EMT and promote metastasis of tumor cells. As an inhibitor of MAOA, the released INH can effectively enhance CD8+ T cell infiltration, block the EMT signaling pathway and remove immunosuppression.