Ultrasound combined with nanobubbles promotes systemic anticancer immunity and augments anti-PD1 efficacy
Background 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 tumo...
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BMJ Publishing Group
2022-03-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/10/3/e003408.full |
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| author | Yang Zhao Jun Tan Jianjun Hu Hongwei Wang Yue Zhang Chi Zhang Yunlong Wang Yan Dong Yanli Guo Juanjuan Ou Houjie Liang Junyi Wang Jiangyi He Kejing Fang Yanrong Chen Ruiyang Zi Chengxiang Liu |
| author_facet | Yang Zhao Jun Tan Jianjun Hu Hongwei Wang Yue Zhang Chi Zhang Yunlong Wang Yan Dong Yanli Guo Juanjuan Ou Houjie Liang Junyi Wang Jiangyi He Kejing Fang Yanrong Chen Ruiyang Zi Chengxiang Liu |
| author_sort | Yang Zhao |
| collection | DOAJ |
| description | Background 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.Methods 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.Results 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.Conclusion 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. |
| format | Article |
| id | doaj-art-b388a33f2f4147a68ab717fa2f0d97e4 |
| institution | DOAJ |
| issn | 2051-1426 |
| language | English |
| publishDate | 2022-03-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-b388a33f2f4147a68ab717fa2f0d97e42025-08-20T03:05:21ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262022-03-0110310.1136/jitc-2021-003408Ultrasound combined with nanobubbles promotes systemic anticancer immunity and augments anti-PD1 efficacyYang Zhao0Jun Tan1Jianjun Hu2Hongwei Wang3Yue Zhang4Chi Zhang5Yunlong Wang6Yan Dong7Yanli Guo8Juanjuan Ou9Houjie Liang10Junyi Wang11Jiangyi He12Kejing Fang13Yanrong Chen14Ruiyang Zi15Chengxiang Liu16Department of Neurosurgery, Peking University International Hospital, Beijing, ChinaDepartment of Oncology, Army Medical University, Chongqing, ChinaDepartment of Computer Science & Engineering, College of Engineering, University of South Carolina, Columbia, South Carolina, USAvice president development1 Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Oncology, Army Medical University, Chongqing, ChinaDepartment of Oncology, Army Medical University, Chongqing, China1 The Institute for Tropical Medicine, School of Basic Medical Sciences, Kunming Medical University, Kunming, Yunnan, ChinaDepartment of Ultrasound, Third Military Medical University Southwest Hospital, Chongqing, ChinaDepartment of Oncology, Army Medical University, Chongqing, ChinaDepartment of Oncology, Army Medical University, Chongqing, ChinaPulmonary and Critical Care Medicine, Peking University Third Hospital, Beijing, ChinaDepartment of Oncology, Army Medical University, Chongqing, ChinaDepartment of Ultrasound, Army Medical University, Chongqing, ChinaDepartment of Oncology, Army Medical University, Chongqing, ChinaDepartment of Oncology, Army Medical University, Chongqing, ChinaDepartment of Oncology, Army Medical University, Chongqing, ChinaBackground 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.Methods 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.Results 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.Conclusion 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.https://jitc.bmj.com/content/10/3/e003408.full |
| spellingShingle | Yang Zhao Jun Tan Jianjun Hu Hongwei Wang Yue Zhang Chi Zhang Yunlong Wang Yan Dong Yanli Guo Juanjuan Ou Houjie Liang Junyi Wang Jiangyi He Kejing Fang Yanrong Chen Ruiyang Zi Chengxiang Liu Ultrasound combined with nanobubbles promotes systemic anticancer immunity and augments anti-PD1 efficacy Journal for ImmunoTherapy of Cancer |
| title | Ultrasound combined with nanobubbles promotes systemic anticancer immunity and augments anti-PD1 efficacy |
| title_full | Ultrasound combined with nanobubbles promotes systemic anticancer immunity and augments anti-PD1 efficacy |
| title_fullStr | Ultrasound combined with nanobubbles promotes systemic anticancer immunity and augments anti-PD1 efficacy |
| title_full_unstemmed | Ultrasound combined with nanobubbles promotes systemic anticancer immunity and augments anti-PD1 efficacy |
| title_short | Ultrasound combined with nanobubbles promotes systemic anticancer immunity and augments anti-PD1 efficacy |
| title_sort | ultrasound combined with nanobubbles promotes systemic anticancer immunity and augments anti pd1 efficacy |
| url | https://jitc.bmj.com/content/10/3/e003408.full |
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