肿瘤细胞治疗研究
英文原题：Tanshinone IIA&Icaritin -MPs regulated vascular normalization and restored tumor-infiltrating T lymphocyte function to boost anti-PD-1 therapy in melanoma lung metastasis.
TSA&ICT-MP 通过调节 ELTD1 促进血管正常化，从而增强 TIL 浸润，并通过靶向 ENPP1 减少腺苷释放，进而增强抗肿瘤免疫。
背景：PD-1抑制剂是治疗黑色素瘤的有前景方案，但超过50%的转移性黑色素瘤患者应答不佳。疗效有限部分源于转移肺组织中血管结构异常和免疫抑制性微环境。 方法：我们开发了基于细胞外囊泡的递送系统Tanshinone IIA与Icaritin-MPs（TSA&ICT-MPs），用于靶向肺转移。通过体内外模型、细胞实验、免疫荧光、免疫组织化学、流式细胞术和质谱流式细胞术，验证TSA&ICT-MPs调节腺苷代谢通路、促进血管正常化、增强TIL（肿瘤浸润淋巴细胞）活性并减少髓源性抑制细胞（MDSC）浸润的效果。 结果：TSA&ICT-MP通过调节ELTD1促进血管正常化，从而增强TIL浸润；同时通过靶向ENPP1减少腺苷释放，增强抗肿瘤免疫。在小鼠模型中，TSA&ICT-MP联合抗PD-1抑制肺转移达70.33%，并延长生存。这一方法为增强黑色素瘤免疫治疗疗效提供了有前景的策略。
BACKGROUND: PD-1 inhibitors are a promising treatment for melanoma, but over 50% of patients with metastatic melanoma do not respond well. This limited efficacy is partly due to the aberrant vascular structure and immunosuppressive microenvironment in metastatic lung tissue. METHODS: We developed an extracellular vesicle-based delivery system Tanshinone IIA & Icaritin -MPs (TSA&ICT-MPs) that targets lung metastases. In vivo in vitro models, cell experiments, immunofluorescence, immunohistochemistry, flow cytometry, and mass spectrometry flow cytometry were used to validate the efficacy of TSA&ICT-MPs in promoting vascular normalization, enhancing the activity of tumor-infiltrating lymphocytes (TILs), and reducing myeloid-derived inhibitory cell (MDSC) infiltration by modulating the adenosine metabolic pathway. RESULTS: TSA&ICT-MP contributes to vascular normalization by modulating ELTD1, thereby enhancing TIL infiltration, and reduces adenosine release by targeting ENPP1, thus enhancing anti-tumor immunity. Combining TSA&ICT-MP with -PD-1 achieved a 70.33% suppression rate of lung metastasis and prolonged survival in murine models. This approach offers a promising strategy to enhance the efficacy of melanoma immunotherapy.
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