瘤内浸润调节性T细胞（Tregs）是瘤内重要的免疫检查点，抑制了肿瘤免疫功能，是肿瘤免疫治疗失败的关键因素之一。因此，清除肿瘤内的Tregs或抑制其功能，是免疫检查点抑制技术用于肿瘤治疗的新策略。传统注射抗体的方法，不能选择性清除瘤内Tregs，会引起全身性免疫反应。本项目中，我们选择在第二红外窗口具有优异光热转换能力的W18O49纳米微粒，在其表面修饰肿瘤组织微环境敏感的PEG层以及靶向Tregs的CD39单抗；或者制备“集束炸弹”型W18O49-明胶复合纳米药物。这些材料可靶向聚集到肿瘤组织，在激光照射下，选择性清除瘤内Tregs，恢复机体的肿瘤免疫功能，达到治疗肿瘤的目的。本项目将纳米药物的靶向性，光热治疗的空间选择性，肿瘤的免疫治疗有机结合，建立清除瘤内浸润性Tregs的新型纳米光热免疫治疗体系，定点清除瘤内浸润的Tregs，恢复生物体的肿瘤免疫功能，为恶性肿瘤的治疗提供新思路。

Tumour infiltrated regulatory T cells (Tregs), contribute primarily to the tumour immune-suppression，immune escape and the failure of cancer immunotherapy (CIT). On this basis, therapeutic methods to deplete Tregs’ or inhibit the function of Tregs were thought to be the most promising strategy to enhance the therapeutic effect of CIT. Although, traditional methods to deplete Tregs or inhibit the function of Tregs, such as systemic administration of CD25 specific antibody, have been proved to be the most promising strategy to enhance the therapeutic effect against tumors, the lethal side effect restricts their clinical application. In this project, we proposed a novel method of immuno-photothermal therapy (IPTT) to selectively deplete the tumour infiltrated Tregs by anti-CD39 antibody modified W18O49 NPs (WOAA NPs). CD39 is an integral membrane, constitutively expressed on the surface the CD4+ CD25+ Tregs, and recently thought to play a pivotal role in the tumour escape from immune surveillance. W18O49 NPs have been applied in the photothermal ablation of cancer cells because of their unique high light absorption efficacy in NIR-II region (1000-1500 nm). Compared with traditional PTT or immunotherapy alone, this IPTT method has several merits: (1) IPTT significantly reduces the administration dosage to eliminate the infiltrated Tregs, which accounts for relatively small percentage of cells in tumour; (2) Modest elevation of temperature in tumour lesion stimulates favorable immunity without suffering from promoted invasion and tumour metastasis generated by traditional PTT in cancer therapy (3) Activation of anti-tumour immunity and alleviation of tumour immune-suppressive microenvironment can be achieved simultaneously, resulting in long lasting immune surveillance. Collectively, we hope our strategy integrating intra-tumoural Tregs depletion and photo-thermo therapy (PTT) can play a vital role in cancer therapy.