加味阳和汤通过 CXCR3 配体介导的趋化作用增强非小细胞肺癌瘤内 CD8(+) TIL 浸润并提高放疗疗效

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.

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.

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.