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通过混合M1巨噬细胞/肿瘤裂解物水凝胶对肿瘤抗原依赖性免疫疗法进行调控。

Regulation of tumor antigens-Dependent immunotherapy via the hybrid M1 macrophage/tumor lysates Hydrogel.

作者信息

Li Zeyang, Zhan Jiani, Zheng Yinuo, Luo Yingli, Yu Xiaoming, Chen Haha

机构信息

Department of Ultrasonic Imaging, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.

The First School of Medicine, School of Information and Engineering, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.

出版信息

Heliyon. 2024 Sep 6;10(18):e37521. doi: 10.1016/j.heliyon.2024.e37521. eCollection 2024 Sep 30.

Abstract

Tumor treatment poses a significant obstacle in contemporary healthcare. Using components derived from a patient's own cellular and tissue materials to prepare hydrogels and other therapeutic systems has become a novel therapeutic approach, drawing considerable interest for their applicability in basic research on cancer immunotherapy. These hydrogels can engage with cellular components directly and offer a supportive scaffold, aiding in the normalization of tumor tissues. Additionally, their superior capability for encapsulating targeted anti-tumor medications amplifies treatment effectiveness. Given their origin from a patient's own cells, these hydrogels circumvent the risks of immune rejection by the body and severe side effects typically associated with foreign substance. In this study, we developed a composite hydrogel constructed by the cellular lysates of autologous tumor cells and M1 macrophages. This combination promoted the M2 macrophages polarization to the M1 phenotype. Subsequently, the polarized M1 macrophages infiltrated into the hydrogel and can directly capture tumor antigens. As antigen-presenting cells, M1 macrophages can stimulate the production of antigen-specific T cells to kill tumor cells. This work proposes a dual-benefit research strategy that not only polarizes M2 macrophages but also enhances immune activation, boosting T cell-mediated tumor-killing effects. This approach offers a new therapeutic option for clinical cancer immunotherapy.

摘要

肿瘤治疗是当代医疗保健中的一个重大障碍。利用患者自身细胞和组织材料衍生的成分制备水凝胶和其他治疗系统已成为一种新型治疗方法,因其在癌症免疫治疗基础研究中的适用性而备受关注。这些水凝胶可以直接与细胞成分相互作用,并提供一个支持性支架,有助于肿瘤组织的正常化。此外,它们卓越的包封靶向抗肿瘤药物的能力增强了治疗效果。鉴于这些水凝胶来源于患者自身细胞,它们规避了身体免疫排斥的风险以及通常与外来物质相关的严重副作用。在本研究中,我们开发了一种由自体肿瘤细胞和M1巨噬细胞的细胞裂解物构建的复合水凝胶。这种组合促进了M2巨噬细胞向M1表型的极化。随后,极化的M1巨噬细胞浸润到水凝胶中并能直接捕获肿瘤抗原。作为抗原呈递细胞,M1巨噬细胞可以刺激抗原特异性T细胞的产生以杀死肿瘤细胞。这项工作提出了一种双重获益的研究策略,不仅使M2巨噬细胞极化,还增强免疫激活,提高T细胞介导的肿瘤杀伤作用。这种方法为临床癌症免疫治疗提供了一种新的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae61/11414488/960173c46c3f/ga1.jpg

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