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基于黑磷的光热疗法联合αCD47介导的免疫检查点阻断用于增强癌症免疫治疗

Black phosphorus-based photothermal therapy with aCD47-mediated immune checkpoint blockade for enhanced cancer immunotherapy.

作者信息

Xie Zhongjian, Peng Minhua, Lu Ruitao, Meng Xiangying, Liang Weiyuan, Li Zhongjun, Qiu Meng, Zhang Bin, Nie Guohui, Xie Ni, Zhang Han, Prasad Paras N

机构信息

Shenzhen International Institute for Biomedical Research, Shenzhen, 518116 Guangdong PR China.

Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055 Guangdong PR China.

出版信息

Light Sci Appl. 2020 Sep 15;9:161. doi: 10.1038/s41377-020-00388-3. eCollection 2020.

Abstract

Here, we describe a combination strategy of black phosphorus (BP)-based photothermal therapy together with anti-CD47 antibody (aCD47)-based immunotherapy to synergistically enhance cancer treatment. Tumour resistance to immune checkpoint blockades in most cancers due to immune escape from host surveillance, along with the initiation of metastasis through immunosuppressive cells in the tumour microenvironment, remains a significant challenge for cancer immunotherapy. aCD47, an agent for CD47/SIRPα axis blockade, induces modest phagocytic activity and a low response rate for monotherapy, resulting in failures in clinical trials. We showed that BP-mediated ablation of tumours through photothermal effects could serve as an effective strategy for specific immunological stimulation, improving the inherently poor immunogenicity of tumours, which is particularly useful for enhancing cancer immunotherapy. BP in combination with aCD47 blockade activates both innate and adaptive immunities and promotes local and systemic anticancer immune responses, thus offering a synergistically enhanced effect in suppression of tumour progression and in inducing abscopal effects for inhibition of metastatic cancers. Our combination strategy provides a promising platform in which photothermal agents could help to enhance the therapeutic efficacy of immunotherapy.

摘要

在此,我们描述了一种基于黑磷(BP)的光热疗法与基于抗CD47抗体(aCD47)的免疫疗法相结合的策略,以协同增强癌症治疗效果。由于肿瘤通过免疫逃逸逃避宿主监视以及通过肿瘤微环境中的免疫抑制细胞引发转移,大多数癌症对免疫检查点阻断产生抗性,这仍然是癌症免疫疗法面临的重大挑战。aCD47是一种用于阻断CD47/SIRPα轴的药物,其诱导的吞噬活性适度且单药治疗的反应率较低,导致临床试验失败。我们表明,BP通过光热效应介导的肿瘤消融可作为一种有效的特异性免疫刺激策略,改善肿瘤固有的低免疫原性,这对于增强癌症免疫疗法尤为有用。BP与aCD47阻断相结合可激活先天性和适应性免疫,并促进局部和全身抗癌免疫反应,从而在抑制肿瘤进展和诱导远隔效应以抑制转移性癌症方面提供协同增强作用。我们的联合策略提供了一个有前景的平台,其中光热剂有助于提高免疫疗法的治疗效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d542/7492464/4cc653bdb791/41377_2020_388_Fig1_HTML.jpg

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