Autophagy Inhibition by Fangji Huangqi Decoction Enhances Tumor Immunogenicity and Potentiates PD-1 Blockade

Fangji Huangqi Decoction (FJHQ), a traditional Chinese medicine formula derived from "Jin Gui Yao Lue," has been reported to exhibit immunomodulatory and anti-inflammatory effects. This study investigates its potential anti-tumor mechanism via the enhancement of CD8⁺ T cell-mediated immunity. In murine B16 melanoma and Lewis lung carcinoma models, FJHQ significantly suppressed tumor growth and enhanced CD8⁺ T cell infiltration and cytotoxicity. CD8⁺ T cell depletion abrogated these effects, confirming their necessity. In vitro, FJHQ treatment augmented antigen presentation by tumor cells through upregulation of MHC-I expression, leading to improved CD8⁺ T cell recognition and killing. Mechanistically, FJHQ inhibited autophagic flux in tumor cells, as evidenced by mCherry-GFP-LC3 reporter assays and electron microscopy, resulting in impaired lysosomal function and elevated MHC-I levels. Furthermore, combining FJHQ with anti-PD-1 therapy synergistically promoted CD8⁺ T cell activity, increased granzyme B and IFN-γ expression, and induced substantial tumor regression. These findings demonstrate that FJHQ enhances antitumor immunity by suppressing autophagy and elevating MHC-I expression, thereby sensitizing tumors to PD-1 blockade. FJHQ represents a promising immunoadjuvant for cancer therapy.