食管鳞状细胞癌（ESCC）的免疫疗法在疗效上表现出显着的差异。同时，最近的研究强调了 circRNA 对 ESCC 肿瘤微环境的影响。为了进一步探讨这种关系，我们利用 circRNA、microRNA 和 mRNA 序列数据集构建了一个全面的免疫相关 circRNA-microRNA-mRNA 网络，揭示了 ESCC 中竞争的内源性 RNA (ceRNA) 作用。该网络包含 16 个环状 RNA、13 个 microRNA 和 1,560 个 mRNA。加权基因共表达分析确定了免疫相关模块，特别是癌症相关成纤维细胞（CAF）和骨髓源性抑制细胞模块，与免疫和干性评分显着相关。其中，CAF模块在细胞外基质功能中发挥着至关重要的作用，可以有效区分ESCC患者。 CAF 内的四个中心胶原蛋白家族基因与 CAF、巨噬细胞浸润和 T 细胞排斥密切相关。内部测序和 RT-qPCR 验证了它们的表达升高。我们还将 CAF 模块靶向药物确定为潜在的 ESCC 治疗方法。总之，我们建立了一个免疫相关的 circRNA-miRNA-mRNA 网络，不仅阐明了 ceRNA 的功能，而且还强调了 circRNA 通过胶原蛋白基因靶向参与 CAF。这些发现有望预测食管鳞癌的免疫状况和治疗反应，最终有助于更加个性化和有效的临床决策。

Immunotherapy for esophageal squamous cell carcinoma (ESCC) exhibits notable variability in efficacy. Concurrently, recent research emphasizes circRNAs' impact on the ESCC tumor microenvironment. To further explore the relationship, we leveraged circRNA, microRNA, and mRNA sequence datasets to construct a comprehensive immune-related circRNA-microRNA-mRNA network, revealing competing endogenous RNA (ceRNA) roles in ESCC. The network comprises 16 circular RNAs, 13 microRNAs, and 1,560 mRNAs. Weighted gene co-expression analysis identified immune-related modules, notably cancer-associated fibroblast (CAF) and myeloid-derived suppressor cell modules, correlating significantly with immune and stemness scores. Among them, the CAF module plays a crucial role in extracellular matrix function and effectively discriminates ESCC patients. Four hub collagen family genes within CAF correlated robustly with CAF, macrophage infiltration, and T-cell exclusion. In-house sequencing and RT-qPCR validated their elevated expression. We also identified CAF module-targeting drugs as potential ESCC treatments. In summary, we established an immune-related circRNA-miRNA-mRNA network that not only illuminates ceRNA functionality but also highlights circRNAs' involvement in the CAF through collagen gene targeting. These findings hold promise to predict ESCC immune landscapes and therapy responses, ultimately aiding in more personalized and effective clinical decision-making.