PDF(Pubmed)
Abstract：
Remodeling the tumor microenvironment through reprogramming tumor-associated macrophages (TAMs) and increasing the immunogenicity of tumors via immunogenic cell death (ICD) have been emerging as promising anticancer immunotherapy strategies. However, the heterogeneous distribution of TAMs in tumor tissues and the heterogeneity of the tumor cells make the immune activation challenging. To overcome these dilemmas, a hybrid bacterium with tumor targeting and penetration, TAM polarization, and photothermal conversion capabilities is developed for improving antitumor immunotherapy in vivo. The hybrid bacteria (B.b@QDs) are prepared by loading Ag2S quantum dots (QDs) on the Bifidobacterium bifidum (B.b) through electrostatic interactions. The hybrid bacteria with hypoxia targeting ability can effectively accumulate and penetrate the tumor tissues, enabling the B.b to fully contact with the TAMs and mediate their polarization toward M1 phenotype to reverse the immunosuppressive tumor microenvironment. It also enables to overcome the intratumoral heterogeneity and obtain abundant tumor-associated antigens by coupling tumor penetration of the B.b with photothermal effect of the QDs, resulting in an enhanced immune effect. This strategy that combines B.b-triggered TAM polarization and QD-induced ICD achieved a remarkable inhibition of tumor growth in orthotopic breast cancer.
摘要：
通过重编程肿瘤相关巨噬细胞（TAM）重塑肿瘤微环境和通过免疫原性细胞死亡（ICD）增加肿瘤的免疫原性已成为有前途的抗癌免疫治疗策略。然而,TAMs在肿瘤组织中的异质性分布和肿瘤细胞的异质性使得免疫激活具有挑战性。为了克服这些困境，一种具有肿瘤靶向和渗透的杂交细菌，TAM极化,和光热转化能力被开发用于改善体内抗肿瘤免疫疗法。杂种细菌(B.b@QDs）是通过将Ag2S量子点（QDs）负载在两歧双歧杆菌（B.b)通过静电相互作用。具有缺氧靶向能力的杂合菌可有效蓄积并穿透肿瘤组织,使B.b与TAM充分接触并介导它们向M1表型的极化，以逆转免疫抑制性肿瘤微环境。通过将B.b的肿瘤渗透与QDs的光热效应耦合，还可以克服肿瘤内异质性并获得丰富的肿瘤相关抗原，导致增强的免疫效果。这种结合了B.b触发的TAM极化和QD诱导的ICD的策略在原位乳腺癌中实现了对肿瘤生长的显着抑制。
