Low tumor mutational burden and absence of T cells within the tumor sites are typical characteristics of “cold immune tumors” that paralyzes the immune system. The strategy of reversing “cold tumors” to “hot tumors” infiltrated high degree of T cells in order to activate anti-tumor immunity has attracted lots of attentions. Herein, immunogenic core–shell Au@Se NPs is fabricated by gold-selenium coordination bond to realize nanoparticles-mediated local photothermal-triggered immunotherapy. As expected, incorporation of gold nanostars (AuNSs) with improved photothermal stability and conversion efficiency promotes the disintegration and transformation of selenium nanoparticles (SeNPs), thus leading to enhanced cancer cells apoptosis by producing higher hyperthermia. Moreover, the results of in vivo experiments demonstrate that the synergy between SeNPs-mediated chemotherapy and AuNSs-induced photothermal therapy not only generated a localized antitumor-immune response with excellent cancer killing effect under the presence of tumor-associated antigens, but also effectively reprogrammed the tumor associated macrophages (TAMs) from M2 to M1 phenotype with tumoricidal activity to devour distant tumors. Without a doubt, this study not only provides a potent strategy to reverse the immunosuppressive tumor microenvironment, but also offers a new insight for potential clinical application in tumor immunotherapy.

低的肿瘤突变负担和肿瘤部位内T细胞的缺乏是使免疫系统瘫痪的“冷免疫瘤”的典型特征。为了激活抗肿瘤免疫力，将“冷肿瘤”转变为“热肿瘤”的策略是渗透高度的T细胞，从而引起了人们的广泛关注。在本文中，通过金-硒配位键制造了具有免疫原性的核壳Au @ Se NP，以实现纳米粒子介导的局部光热触发免疫疗法。不出所料，掺入具有改善的光热稳定性和转化效率的金纳米星（AuNSs）会促进硒纳米颗粒（SeNPs）的分解和转化，从而通过产生更高的高温而导致癌细胞凋亡增强。而且，体内结果实验表明，SeNPs介导的化学疗法和AuNSs诱导的光热疗法之间的协同作用不仅在存在肿瘤相关抗原的情况下产生了具有优异的杀癌效果的局部抗肿瘤免疫应答，而且还有效地重新编程了肿瘤相关巨噬细胞（TAM）从M2到M1表型具有吞噬远处肿瘤的杀癌活性。毫无疑问，这项研究不仅为扭转免疫抑制性肿瘤微环境提供了有效的策略，而且为肿瘤免疫治疗中潜在的临床应用提供了新的见识。