Ultrasound combined with nanobubbles promotes systemic anticancer immunity and augments anti-PD1 efficacy.
Ultrasound combined with nanobubbles promotes systemic anticancer immunity and augments anti-PD1 efficacy.
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超声结合纳米气泡促进全身抗癌免疫，增强抗pd1功效。
DOI：
10.1136/jitc-2021-003408
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发表时间：
2022-03
影响因子：
10.9
通讯作者：
Ou J
中科院分区：
文献类型：
--
作者：
Hu J;He J;Wang Y;Zhao Y;Fang K;Dong Y;Chen Y;Zhang Y;Zhang C;Wang H;Tan J;Wang J;Zi R;Liu C;Liang H;Guo Y;Ou J
实体瘤的低免疫原性限制了基于抗程序性细胞死亡蛋白1(anti-PD1)的免疫检查点阻断(ICB)的疗效，因此，只有不到30%的癌症患者表现出应答。目前，对于提高肿瘤免疫原性尚缺乏有效的策略。在RM1(前列腺癌)、MC38(结肠癌)和B16(黑色素瘤)异种移植小鼠模型上，评价了超声刺激纳米气泡(USNB)单独和联合抗PD1抗体的抗肿瘤作用。用流式细胞仪检测抗原提呈细胞和CD8+T细胞的表型。用免疫印迹、流式细胞仪、透射电子显微镜和共聚焦显微镜检测损伤相关分子模式(DAMP)的释放、抗原的释放和肿瘤细胞的坏死。USNB可促进CD8+T细胞的浸润和抗肿瘤活性。联合应用USNB和抗PD1受体阻断剂可提高机体的抗肿瘤免疫功能，对肿瘤完全缓解后的免疫记忆有一定的保护作用。从机制上讲，肿瘤靶向USNB通过超声介导的空化效应导致肿瘤细胞坏死，显著增加肿瘤的湿气释放和肿瘤抗原提呈，从而使肿瘤对ICB治疗增敏。USNB通过重塑肿瘤免疫微环境来提高肿瘤的免疫原性，为临床上免疫原性差的实体瘤的免疫治疗提供了一种有前途的策略。
The poor immunogenicity of solid tumors limits the efficacy ofanti-programmed cell death protein 1 (anti-PD1)-based immune checkpoint blockade (ICB); thus, less than 30% of patients with cancer exhibit a response. Currently, there is still a lack of effective strategies for improving tumor immunogenicity. The antitumor effect of ultrasound-stimulated nanobubbles (USNBs) alone and in combination with an anti-PD1 antibody was evaluated in RM1 (prostate cancer), MC38 (colon cancer) and B16 (melanoma) xenograft mouse models. The phenotypes of antigen-presenting cells and CD8+ T cells were evaluated by flow cytometry. Damage-associated molecular pattern (DAMP) release, antigen release and tumor cell necrosis were assessed via western blot, flow cytometry, transmission electron microscopy and confocal microscopy. USNB promoted the infiltration and antitumor activity of CD8+ T cells. The combination of USNB and anti-PD1 blockade improved systemic antitumor immunity and resulted in an abscopal effect and long-term immune memory protection after complete tumor remission. Mechanistically, tumor-targeting USNB induced tumor cell necrosis through an ultrasound-mediated cavitation effect, which significantly increased DAMP release and tumor antigen presentation, consequently sensitizing tumors to ICB treatment. The administration of USNB increased tumor immunogenicity by remodeling the tumor-immune microenvironment, providing a promising strategy for sensitizing poorly immunogenic solid tumors to immunotherapy in the clinic.
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影响因子：
28.2
作者：
Chen PL;Roh W;Reuben A;Cooper ZA;Spencer CN;Prieto PA;Miller JP;Bassett RL;Gopalakrishnan V;Wani K;De Macedo MP;Austin-Breneman JL;Jiang H;Chang Q;Reddy SM;Chen WS;Tetzlaff MT;Broaddus RJ;Davies MA;Gershenwald JE;Haydu L;Lazar AJ;Patel SP;Hwu P;Hwu WJ;Diab A;Glitza IC;Woodman SE;Vence LM;Wistuba II;Amaria RN;Kwong LN;Prieto V;Davis RE;Ma W;Overwijk WW;Sharpe AH;Hu J;Futreal PA;Blando J;Sharma P;Allison JP;Chin L;Wargo JA
通讯作者：
Wargo JA
影响因子：
13.3
作者：
Lin, Sheng-Yen;Hsieh, Sung-Yuan;Yang, Ning-Sun
通讯作者：
Yang, Ning-Sun
影响因子：
78.8
作者：
Matzner, Pini;Sandbank, Elad;Ben-Eliyahu, Shamgar
通讯作者：
Ben-Eliyahu, Shamgar
影响因子：
64.8
作者：
Jansen, Caroline S.;Prokhnevska, Nataliya;Kissick, Haydn
通讯作者：
Kissick, Haydn
影响因子：
7.3
作者：
Liu D;Jenkins RW;Sullivan RJ
通讯作者：
Sullivan RJ