The efficacy of radiotherapy has not yet achieved optimal results, partially due to insufficient priming and infiltration of effector immune cells within the tumor microenvironment (TME), which often exhibits suppressive phenotypes. In particular, the infiltration of X–C motif chemokine receptor 1 (XCR1)-expressing conventional type-1 dendritic cells (cDC1s), which are critical in priming CD8+ cytotoxic T cells, within the TME is noticeably restricted. Hence, we present a facile methodology for the efficient fabrication of a calcium phosphate hydrogel loaded with X–C motif chemokine ligand 1 (XCL1) to selectively recruit cDC1s. Manganese phosphate microparticles were also loaded into this hydrogel to reprogram the TME via cGAS-STING activation, thereby facilitating the priming of cDC1s propelled specific CD8+ T cells. They also polarize tumor-associated macrophages towards the M1 phenotype and reduce the proportion of regulatory cells, effectively reversing the immunosuppressive TME into an immune-active one. The yielded XCL1@CaMnP gel exhibits significant efficacy in enhancing the therapeutic outcomes of radiotherapy, particularly when concurrently administered with postoperative radiotherapy, resulting in an impressive 60 % complete response rate. Such XCL1@CaMnP gel, which recruits cDC1s to present tumor antigens generated in situ, holds great potential as a versatile platform for enhanced cancer treatment through modulating the immunosuppressive TME.

中文翻译：

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凝胶介导的常规 1 型树突状细胞募集可增强放疗的治疗效果


放疗的疗效尚未达到最佳效果，部分原因是肿瘤微环境（TME）内效应免疫细胞的启动和浸润不足，而肿瘤微环境通常表现出抑制表型。特别是，表达 X-C 基序趋化因子受体 1 (XCR1) 的传统 1 型树突细胞 (cDC1) 在 TME 内的浸润明显受到限制，这些细胞对于启动 CD8+ 细胞毒性 T 细胞至关重要。因此，我们提出了一种简便的方法，用于有效制造负载 X-C 基序趋化因子配体 1 (XCL1) 的磷酸钙水凝胶，以选择性地招募 cDC1。磷酸锰微粒也被加载到该水凝胶中，通过 cGAS-STING 激活对 TME 进行重新编程，从而促进 cDC1 推动的特异性 CD8+ T 细胞的启动。它们还将肿瘤相关巨噬细胞极化为 M1 表型，并减少调节细胞的比例，有效地将免疫抑制性 TME 转变为免疫活性 TME。产生的 XCL1@CaMnP 凝胶在增强放射治疗的治疗效果方面表现出显着的功效，特别是在与术后放射治疗同时进行时，达到了令人印象深刻的 60% 的完全缓解率。这种 XCL1@CaMnP 凝胶可招募 cDC1 以呈递原位生成的肿瘤抗原，作为通过调节免疫抑制 TME 来增强癌症治疗的多功能平台具有巨大潜力。