biostudies-literatureRen HNatural Science Foundation of Jiangxi Province (Jiangxi Province Natural Science Foundation)Natural Science Foundation of Guangdong Province (Guangdong Natural Science Foundation)National Natural Science Foundation of China (National Science Foundation of China)188https://www.ebi.ac.uk/biostudies/studies/S-EPMC10873409biostudies-literatureUnknown7(1)Photothermal therapy (PTT) is a cancer-targeted treatment approach.The occurrence of tumors may be related to microbial infections (Viruses, bacteria, fungi, etc.), which probably provokes anti-tumor immunity. However, T cells in the context of cancer become exhausted and dysfunctional. Galectin-9 (Gal-9) is highly expressed in normal tissues and associates with body immune tolerance, and was firstly evidenced with much higher expression on the primary solid tumors than CD80/86 (B7) and CD274 (PD-L1) here, which suggests that Gal-9 may be a key factor in inhibiting the anti-tumor immunity, and its receptor T cell immunoglobulin and mucin domain 3 (TIM-3) was discovered on the cytotoxic T lymphocytes (CTL) with high expression as well based on the single cell analysis. The immune checkpoint communications showed that the Gal-9/TIM-3 axis played the most vital role on negatively regulating the anti-tumor immunity of CTL for melanoma. Then, we used a novel transdermal photothermal nanosensitizer (FSGG) loading Gal-9 siRNA (FSGG/siGal-9) for knocking the tumor cells down Gal-9 to block the Gal-9/TIM-3 axis and prohibit CTL exhaustion synergizing PTT against melanoma, which evidenced good effects on inhibiting tumor growth and enhancing anti-tumor immunity, named "photothermal immunotherapy". This paper provides a new perspective for tumor prevention and treatment.Communications biologyTumor-targeted nanodrug FSGG/siGal-9 for transdermal photothermal immunotherapy of melanoma.PMC10873409818030642022A151514017820192ACB21027Ren HHao NZhang YHuang WHe WXu HZhang CfalseTumor-targeted nanodrug FSGG/siGal-9 for transdermal photothermal immunotherapy of melanoma.Photothermal therapy (PTT) is a cancer-targeted treatment approach.The occurrence of tumors may be related to microbial infections (Viruses, bacteria, fungi, etc.), which probably provokes anti-tumor immunity. However, T cells in the context of cancer become exhausted and dysfunctional. Galectin-9 (Gal-9) is highly expressed in normal tissues and associates with body immune tolerance, and was firstly evidenced with much higher expression on the primary solid tumors than CD80/86 (B7) and CD274 (PD-L1) here, which suggests that Gal-9 may be a key factor in inhibiting the anti-tumor immunity, and its receptor T cell immunoglobulin and mucin domain 3 (TIM-3) was discovered on the cytotoxic T lymphocytes (CTL) with high expression as well based on the single cell analysis. The immune checkpoint communications showed that the Gal-9/TIM-3 axis played the most vital role on negatively regulating the anti-tumor immunity of CTL for melanoma. Then, we used a novel transdermal photothermal nanosensitizer (FSGG) loading Gal-9 siRNA (FSGG/siGal-9) for knocking the tumor cells down Gal-9 to block the Gal-9/TIM-3 axis and prohibit CTL exhaustion synergizing PTT against melanoma, which evidenced good effects on inhibiting tumor growth and enhancing anti-tumor immunity, named "photothermal immunotherapy". This paper provides a new perspective for tumor prevention and treatment.2024-01-01T00:00:00Z2024 Feb2024-11-12T05:21:36.418Z2024-11-12T05:21:36.418ZS-EPMC108734093836608310.1038/s42003-024-05891-6