Abstract：
An obstacle in current tumor immunotherapies lies in the challenge of achieving sustained and tumor-targeting T cell immunity, impeded by the limited antigen processing and cross-presentation of tumor antigens. Here, we propose a hydrogel-based multicellular immune factory within the body that autonomously converts tumor cells into an antitumor vaccine. Within the body, the scaffold, formed by a calcium-containing chitosan hydrogel complex (ChitoCa) entraps tumor cells and attracts immune cells to establish a durable and multicellular microenvironment. Within this context, tumor cells are completely eliminated by antigen-presenting cells (APCs) and processed for cross-antigen presentation. The regulatory mechanism relies on the Mincle receptor, a cell-phagocytosis-inducing C-type lectin receptor specifically activated on ChitoCa-recruited APCs, which serves as a recognition synapse, facilitating a tenfold increase in tumor cell engulfment and subsequent elimination. The ChitoCa-induced tumor cell processing further promotes the cross-presentation of tumor antigens to prime protective CD8+ T cell responses. Therefore, the ChitoCa treatment establishes an immune niche within the tumor microenvironment, resulting in effective tumor regression either used alone or in combination with other immunotherapies. This hydrogel-induced immune factory establishes a functional organ-like multicellular colony for tumor-specific immunotherapy, paving the way for innovative strategies in cancer treatment.
摘要：
当前肿瘤免疫疗法的一个障碍在于实现持续和肿瘤靶向T细胞免疫的挑战。受到有限的抗原加工和肿瘤抗原交叉呈递的阻碍。这里,我们提出了一种基于水凝胶的体内多细胞免疫工厂，它可以自主地将肿瘤细胞转化为抗肿瘤疫苗。在身体内,脚手架，由含钙的壳聚糖水凝胶复合物（ChitoCa）形成，可捕获肿瘤细胞并吸引免疫细胞以建立持久的多细胞微环境。在此背景下,肿瘤细胞被抗原提呈细胞(APC)完全消除,并被处理用于交叉抗原呈递.调节机制依赖于Mincle受体，在ChitoCa募集的APC上特异性激活的诱导细胞吞噬的C型凝集素受体，作为识别突触，促进肿瘤细胞吞噬和随后的消除的十倍增加。ChitoCa诱导的肿瘤细胞加工进一步促进肿瘤抗原的交叉呈递以引发保护性CD8+T细胞应答。因此,ChitoCa治疗在肿瘤微环境中建立免疫生态位，导致有效的肿瘤消退单独使用或与其他免疫疗法联合使用。这种水凝胶诱导的免疫工厂建立了一个功能器官样的多细胞集落，用于肿瘤特异性免疫治疗，为癌症治疗的创新策略铺平道路。
