Fibroblasts have a considerable functional and molecular heterogeneity and can play various roles in the tumor microenvironment. Here we identify a pro-tumorigenic IL1R1⁺, IL-1-high-signaling subtype of fibroblasts, using multiple colorectal cancer (CRC) patient single cell sequencing datasets. This subtype of fibroblasts is linked to T cell and macrophage suppression and leads to increased cancer cell growth in 3D co-culture assays. Furthermore, both a fibroblast-specific IL1R1 knockout and IL-1 receptor antagonist Anakinra administration reduce tumor growth in vivo. This is accompanied by reduced intratumoral Th17 cell infiltration. Accordingly, CRC patients who present with IL1R1-expressing cancer-associated-fibroblasts (CAFs), also display elevated levels of immune exhaustion markers, as well as an increased Th17 score and an overall worse survival. Altogether, this study underlines the therapeutic value of targeting IL1R1-expressing CAFs in the context of CRC.

成纤维细胞具有相当大的功能和分子异质性，可以在肿瘤微环境中发挥多种作用。在这里，我们使用多个结直肠癌 (CRC) 患者单细胞测序数据集鉴定了成纤维细胞的促肿瘤 IL1R1 ^{+ 、IL-1 高信号亚型。}这种成纤维细胞亚型与 T 细胞和巨噬细胞抑制有关，并导致 3D 共培养测定中癌细胞生长增加。此外，成纤维细胞特异性IL1R1敲除和 IL-1 受体拮抗剂 Anakinra 给药均可减少体内肿瘤生长。这伴随着瘤内 Th17 细胞浸润的减少。因此，存在表达IL1R1的癌症相关成纤维细胞 (CAF) 的 CRC 患者也表现出免疫耗竭标志物水平升高、Th17 评分升高和总体生存率较差。总而言之，这项研究强调了针对 CRC 背景下表达 IL1R1 的 CAF 的治疗价值。