Deziyangxin suppresses non-small cell lung cancer through remodeling of the tumor immune microenvironment

Deziyangxin (DZYX) is a classical Tibetan multi-herb prescription recorded in Jing Zhu Ben Cao and traditionally used for conditions characterized by blood stasis, phlegm-heat accumulation, and tumor-like masses. Despite its long-standing clinical use, the pharmacological basis underlying its potential anti-tumor activity remains insufficiently understood. This study aimed to evaluate the anti-tumor efficacy of DZYX in non-small cell lung cancer (NSCLC) and to explore its potential mechanisms with emphasis on tumor immune microenvironment modulation. Serum pharmacochemistry was performed using LC–MS/MS to identify circulating constituents of DZYX. A syngeneic Lewis lung carcinoma (LLC) mouse model was established in mice, which were treated with DZYX by oral gavage at 78.5 mg/kg or 157 mg/kg for 25 days. Tumor growth and histopathology were evaluated, while transcriptomic analysis, network pharmacology, flow cytometry, and immunohistochemistry were used to investigate molecular pathways and immune cell infiltration. LC–MS/MS identified 167 circulating components derived from DZYX. DZYX treatment significantly suppressed tumor growth and induced tumor necrosis in LLC-bearing mice. Transcriptomic and enrichment analyses indicated modulation of chemokine signaling, T-cell activation, and innate immune pathways. Flow cytometry and immunohistochemistry further demonstrated increased infiltration of CD4+ and CD8+ T cells, NK cells, and B cells within tumor tissues and spleens. Enhanced intratumoral Granzyme B and IFN-γ signals suggested increased cytotoxic immune activity. DZYX exerts anti-tumor activity in NSCLC associated with remodeling of the tumor immune microenvironment and multi-pathway molecular regulation. These findings provide mechanistic support for the traditional use of DZYX in tumor-related disorders and highlight its potential as an immunomodulatory candidate for lung cancer therapy. • DZYX markedly inhibits NSCLC growth, supporting its traditional therapeutic use. • LC–MS/MS identified 167 serum-absorbed constituents as active material basis. • DZYX increases CD4 + , CD8 + T-cell and NK-cell infiltration into tumors. • DZYX downregulates CXCL1/2 and CCL2 to reverse immune exclusion.