Autophagy-amplifying nanoparticles evoke immunogenic cell death combined with anti-PD-1/PD-L1 for residual tumors immunotherapy after RFA.
Autophagy-amplifying nanoparticles evoke immunogenic cell death combined with anti-PD-1/PD-L1 for residual tumors immunotherapy after RFA.
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DOI：
10.1186/s12951-023-02067-y
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发表时间：
2023-10-03
影响因子：
10.2
通讯作者：
Su, Zhongzhen
中科院分区：
文献类型：
--
作者：
Zhang, Shushan;Huang, Yongquan;Pi, Songying;Chen, Hui;Ye, Feile;Wu, Chaoqun;Li, Liujun;Ye, Qing;Lin, Yuhong;Su, Zhongzhen
关键词：
不完全射频消融（IRFA）在残留肿瘤细胞中引发轻度保护性自噬，并导致免疫抑制微环境。这加速了残留肿瘤的复发，并导致抗PD-1/PDL 1治疗的耐药性，这给残留肿瘤的免疫治疗带来了巨大的临床挑战。轻度自噬激活可以促进癌细胞存活，而自噬的进一步扩增有助于免疫原性细胞死亡（ICD）。为此，我们构建了负载有STF 62247或STF 62247和BMS 202两者的活性靶向沸石咪唑酯骨架-8（ZIF-8）纳米颗粒（NP），即STF62247@ZIF-8/PEG-FA（SZP）或STF 62247-BMS202@ZIF-8/PEG-FA（SBZP）NP。我们发现，SZP纳米颗粒抑制增殖和刺激凋亡的残余肿瘤细胞暴露于亚致死热应激中的自噬依赖的方式。进一步的研究发现，SZP纳米颗粒可以放大残留肿瘤细胞中的自噬并诱发其ICD，从而显著促进树突状细胞（DC）的成熟。通过疫苗接种实验，我们首次发现热+ SZP处理的疫苗接种可以有效抑制新肿瘤的生长，并建立长期免疫记忆。SBZP纳米粒能显著促进残余肿瘤细胞的ICD，明显激活抗肿瘤免疫微环境，显著抑制残余肿瘤的生长。因此，放大的自噬与抗PD-1/PDL 1治疗相结合可能是治疗IRFA后残留肿瘤的新策略。在线版本包含补充材料，可通过10.1186/s12951-023-02067-y获得。
Incomplete radiofrequency ablation (IRFA) triggers mild protective autophagy in residual tumor cells and results in an immunosuppressive microenvironment. This accelerates the recurrence of residual tumors and causes resistance to anti-PD-1/PDL1 therapy, which bringing a great clinical challenge in residual tumors immunotherapy. Mild autophagy activation can promote cancer cell survival while further amplification of autophagy contributes to immunogenic cell death (ICD). To this regard, we constructed active targeting zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs) loaded with STF62247 or both STF62247 and BMS202, namely STF62247@ZIF-8/PEG-FA (SZP) or STF62247-BMS202@ZIF-8/PEG-FA (SBZP) NPs. We found that SZP NPs inhibited proliferation and stimulated apoptosis of residual tumor cells exposed to sublethal heat stress in an autophagy-dependent manner. Further results discovered that SZP NPs could amplify autophagy in residual tumor cells and evoke their ICD, which dramatically boosted the maturation of dendritic cells (DCs). Through vaccination experiments, we found for the first time that vaccination with heat + SZP treatment could efficiently suppress the growth of new tumors and establish long-term immunological memory. Furthermore, SBZP NPs could remarkably promote the ICD of residual tumor cells, obviously activate the anti-tumor immune microenvironment, and significantly inhibit the growth of residual tumors. Thus, amplified autophagy coupled with anti-PD-1/PDL1 therapy is potentially a novel strategy for treating residual tumors after IRFA. The online version contains supplementary material available at 10.1186/s12951-023-02067-y.
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DOI：
10.1038/s41580-023-00585-z
发表时间：
2023-08
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
7.3
作者：
Janji B;Berchem G;Chouaib S
通讯作者：
Chouaib S
自噬调节激活冷肿瘤微环境以改善癌症免疫治疗
影响因子：
7.3
作者：
Jin, Zhicheng;Sun, Xuefeng;Wang, Yaoyao;Zhou, Chao;Yang, Haihua;Zhou, Suna
通讯作者：
Zhou, Suna
影响因子：
6.6
作者：
Obara, Koichi;Matsumoto, Nobuyuki;Itoh, Fumio
通讯作者：
Itoh, Fumio
影响因子：
3.8
作者：
Kouriba, Bourema;Arama, Charles;Djimde, Abdoulaye
通讯作者：
Djimde, Abdoulaye