Journal of ethnopharmacology · 2025
Jiawei Yanghe Decoction augments intratumoral CD8+ TIL infiltration and enhances radiotherapy efficacy in non-small cell lung cancer through CXCR3 ligand-mediated chemotaxis.
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Shen Huimin, Jiang Yuwei, Wang Lei, Hu Zhuannan, Zhang Shaoyan, Cui Jie, Shao Chenglong, Li Cui, Wang Yu, Lu Zhenhui, Huang Xing
Аннотация
ETHNOPHARMACOLOGICAL RELEVANCE: Jiawei Yanghe Decoction (JWYHD)-an optimized formulation derived from the classical Chinese medicine formula Yanghe Decoction, has been clinically used to treat various autoimmune diseases, granulomatous disorders (e.g., sarcoidosis), and asthma. However, its therapeutic potential in non-small cell lung cancer (NSCLC) remains unexplored.
AIM OF THE STUDY: The present study aims to investigate the therapeutic efficacy of JWYHD against NSCLC and elucidate its underlying mechanisms of action.
MATERIALS AND METHODS: A Lewis lung carcinoma (LLC) mouse model was established to evaluate tumor growth inhibition. Transcriptome sequencing, qPCR, flow cytometry, and immunohistochemistry were utilized to analyze chemokine expression (CXCL9, CXCL11) and immune cell spatial infiltration (CD3+, CD8+ T cells) in tumor tissues. Transwell migration assays were performed to validate CXCL9/11-mediated chemotaxis of CD8+ T cells, While Western blotting evaluated JAK2-STAT3 signaling pathway activation.
RESULTS: JWYHD combined with radiotherapy (RT) induced significant tumor growth suppressiom, achieving complete regression (25 % incidence) with sustained disease-free survival during longitudinal monitoring. The combination therapy upregulated the expression of IL-2 receptor family genes (IL-2RA, IL-2RB, IL-2RG) and chemokines (CXCL9, CXCL11) in tumor microenvironment, which correlated with enhanced CD8+ T cell infiltration (p < 0.01 vs. RT alone). Transwell assays demonstrated that the combined treatment enhanced CD8+ T cell migration and cytotoxicity, which was dependent on CXCL9/11. Furthermore, JWYHD suppressed RT-induced activation of the JAK2-STAT3 pathway, alleviated immunosuppression, and improved antitumor efficacy.
CONCLUSIONS: JWYHD might enhance the antitumor immune response to RT by inhibiting the JAK2-STAT3 pathway and upregulating chemokine expression, promoting CD8+ T cell infiltration and activation.
AIM OF THE STUDY: The present study aims to investigate the therapeutic efficacy of JWYHD against NSCLC and elucidate its underlying mechanisms of action.
MATERIALS AND METHODS: A Lewis lung carcinoma (LLC) mouse model was established to evaluate tumor growth inhibition. Transcriptome sequencing, qPCR, flow cytometry, and immunohistochemistry were utilized to analyze chemokine expression (CXCL9, CXCL11) and immune cell spatial infiltration (CD3+, CD8+ T cells) in tumor tissues. Transwell migration assays were performed to validate CXCL9/11-mediated chemotaxis of CD8+ T cells, While Western blotting evaluated JAK2-STAT3 signaling pathway activation.
RESULTS: JWYHD combined with radiotherapy (RT) induced significant tumor growth suppressiom, achieving complete regression (25 % incidence) with sustained disease-free survival during longitudinal monitoring. The combination therapy upregulated the expression of IL-2 receptor family genes (IL-2RA, IL-2RB, IL-2RG) and chemokines (CXCL9, CXCL11) in tumor microenvironment, which correlated with enhanced CD8+ T cell infiltration (p < 0.01 vs. RT alone). Transwell assays demonstrated that the combined treatment enhanced CD8+ T cell migration and cytotoxicity, which was dependent on CXCL9/11. Furthermore, JWYHD suppressed RT-induced activation of the JAK2-STAT3 pathway, alleviated immunosuppression, and improved antitumor efficacy.
CONCLUSIONS: JWYHD might enhance the antitumor immune response to RT by inhibiting the JAK2-STAT3 pathway and upregulating chemokine expression, promoting CD8+ T cell infiltration and activation.
Предметные рубрики MeSH
AnimalsDrugs, Chinese HerbalReceptors, CXCR3CD8-Positive T-LymphocytesMice, Inbred C57BLLung NeoplasmsMiceCarcinoma, Non-Small-Cell LungCarcinoma, Lewis LungCell Line, TumorJanus Kinase 2STAT3 Transcription FactorChemokine CXCL11Lymphocytes, Tumor-InfiltratingChemotaxisChemokine CXCL9MaleSignal Transduction