Combination of SH003 and paclitaxel modulates tumor microenvironment and inhibits metastasis of metastatic melanoma.

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.