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Eliciting an Immunostimulatory Tumor Microenvironment to Enhance the Antitumor Efficacy by Targeted Cancer Immunotherapy
Advanced Therapeutics ( IF 3.7 ) Pub Date : 2022-06-29 , DOI: 10.1002/adtp.202200070 Ya‐Xuan Zhang 1, 2 , Jun‐Jie Zhang 1 , Wei Wang 1 , Xiao‐Ying Guo 3 , Li‐Shuang Hou 1 , Tang‐Rui Zhang 1 , Bao‐Long Wang 1 , Fang Kou 1 , Meng‐Lei Huan 1 , Wei He 4 , Si‐Yuan Zhou 1 , Bang‐Le Zhang 1
Advanced Therapeutics ( IF 3.7 ) Pub Date : 2022-06-29 , DOI: 10.1002/adtp.202200070 Ya‐Xuan Zhang 1, 2 , Jun‐Jie Zhang 1 , Wei Wang 1 , Xiao‐Ying Guo 3 , Li‐Shuang Hou 1 , Tang‐Rui Zhang 1 , Bao‐Long Wang 1 , Fang Kou 1 , Meng‐Lei Huan 1 , Wei He 4 , Si‐Yuan Zhou 1 , Bang‐Le Zhang 1
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Tumor-associated macrophages (TAMs) in tumor microenvironment represent an ideal therapeutic target for cancer immunotherapy. A targeted cancer immunotherapy strategy through reprogramming M2 macrophages to reverse the immunosuppressive microenvironment is proposed and the antitumor effects via targeted immunostimulatory therapy are evaluated. The developed M2-macrophage-targeted nanoparticles (M2-TNPs) can specially target and reprogram the M2 macrophages via polarization to the antitumor M1 phenotype. Compared with nontargeted nanoparticles, M2-TNPs loading zoledronic acid can specifically be recognized by M2 macrophages but not other macrophages and mounted productive antitumor responses, showing enhanced antitumor efficacy by targeted immunostimulation in vitro and in vivo. Moreover, when combining the chemotherapeutic drug dacarbazine with M2-TNPs for treatment of melanoma, a dramatic synergistic effect in cancer therapy through eliciting an immunostimulatory tumor microenvironment to restore the antitumor immunity is demonstrated. These studies provide preclinical evidence that targeted TAM-reprogramming treatment strategies can hold tremendous promise in cancer immunotherapy.
中文翻译：
通过靶向癌症免疫疗法引发免疫刺激性肿瘤微环境以增强抗肿瘤功效
肿瘤微环境中的肿瘤相关巨噬细胞（TAM）代表了癌症免疫治疗的理想治疗靶点。提出了一种通过重编程M2巨噬细胞来逆转免疫抑制微环境的靶向癌症免疫治疗策略，并评估了靶向免疫刺激治疗的抗肿瘤效果。开发的 M2 巨噬细胞靶向纳米粒子 (M2-TNPs) 可以通过极化将 M2 巨噬细胞特异性靶向并重新编程为抗肿瘤 M1 表型。与非靶向纳米颗粒相比，负载唑来膦酸的 M2-TNPs 可以被 M2 巨噬细胞特异性识别，但不能被其他巨噬细胞识别，并产生有效的抗肿瘤反应，通过体外和体内的靶向免疫刺激显示出增强的抗肿瘤功效。而且，当化疗药物达卡巴嗪与 M2-TNPs 联合治疗黑色素瘤时，通过引发免疫刺激性肿瘤微环境恢复抗肿瘤免疫，在癌症治疗中显示出显着的协同效应。这些研究提供了临床前证据，表明靶向 TAM 重编程治疗策略在癌症免疫治疗中具有巨大的前景。
更新日期：2022-06-29
中文翻译：
通过靶向癌症免疫疗法引发免疫刺激性肿瘤微环境以增强抗肿瘤功效
肿瘤微环境中的肿瘤相关巨噬细胞（TAM）代表了癌症免疫治疗的理想治疗靶点。提出了一种通过重编程M2巨噬细胞来逆转免疫抑制微环境的靶向癌症免疫治疗策略，并评估了靶向免疫刺激治疗的抗肿瘤效果。开发的 M2 巨噬细胞靶向纳米粒子 (M2-TNPs) 可以通过极化将 M2 巨噬细胞特异性靶向并重新编程为抗肿瘤 M1 表型。与非靶向纳米颗粒相比，负载唑来膦酸的 M2-TNPs 可以被 M2 巨噬细胞特异性识别，但不能被其他巨噬细胞识别，并产生有效的抗肿瘤反应，通过体外和体内的靶向免疫刺激显示出增强的抗肿瘤功效。而且，当化疗药物达卡巴嗪与 M2-TNPs 联合治疗黑色素瘤时，通过引发免疫刺激性肿瘤微环境恢复抗肿瘤免疫，在癌症治疗中显示出显着的协同效应。这些研究提供了临床前证据，表明靶向 TAM 重编程治疗策略在癌症免疫治疗中具有巨大的前景。
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