Abstract
Developing therapeutic strategies to overcome immune evasion and resistance posed by the tumor microenvironment (TME) in advanced melanoma remains a significant challenge. This study evaluated therapeutic efficacy of an anticancer herbal extract SH003 combined with Paclitaxel (PTX) in a metastatic melanoma model. Results indicated that the combined therapy of SH003 and PTX not only bolstered antitumor immune responses by reducing influx of regulatory T cells (Tregs) and enhancing infiltration of cytotoxic T cells within the TME, but also significantly curtailed tumor growth and metastasis. Notably, the combined therapy of SH003 and PTX effectively inhibited the EGFR/JAK2/STAT3 and PI3K/AKT/mTOR signaling pathways, which are closely associated with tumor cell survival. Additionally, it reduced the expression of markers associated with metastasis, such as MMP-2, MMP-9, N-cadherin, CXCL9, and CXCL10. These findings suggest that SH003 in combination with PTX can reshape the TME, improve immune cell infiltration, and enhance antitumor immunity, offering a promising strategy to improve therapeutic outcomes of metastatic melanoma.