结直肠癌肝转移（CRLM）的器官特异性免疫抑制微环境是免疫治疗抵抗的关键诱因。本文基于单细胞RNA测序、空间转录组学等技术发现，CRLM病灶中高表达分泌型磷蛋白1（SPP1⁺）巨噬细胞与癌症相关成纤维细胞（CAF）形成功能轴，通过代谢重编程、细胞外基质重塑及信号交叉对话构建免疫抑制生态位，伴随髓系细胞扩增、T细胞耗竭及免疫检查点分子上调。当前领域仍存在核心争议与空白：SPP1⁺巨噬细胞“库普弗细胞衍生”与“单核细胞衍生”的发育路径争议尚未明确，代谢干预的临床前疗效与临床转化差距亟待缩小，调节性T细胞的T细胞受体（TCR）克隆型起源及白细胞介素（IL）-10浓度梯度与CD8⁺ T细胞耗竭的定量关系仍不清晰。针对上述机制，本文梳理了精准靶向免疫抑制细胞、代谢-免疫协同干预等策略，并展望多组学指导的个体化治疗方向，为克服CRLM的免疫治疗困境提供理论支撑。

The organ-specific immunosuppressive microenvironment of colorectal liver metastasis (CRLM) is a key cause of immunotherapy resistance. Based on single-cell RNA sequencing and spatial transcriptomics, we found that SPP1⁺ macrophages formed a functional axis with cancer-associated fibroblast (CAF) in CRLM foci, and constructed an immunosuppressive niche through metabolic reprogramming, extracellular matrix remodeling, and signal cross-talk. It is accompanied by myeloid cell expansion, T cell exhaustion, and up-regulation of immune checkpoint molecules. There are still core controversies and gaps in the current field: the developmental pathway of “Kupffer cell derivation” and “monocyte derivation” of SPP1⁺ macrophages is still controversial. The gap between the preclinical efficacy and clinical transformation of metabolic intervention needs to be urgently narrowed. The origin of TCR clonotypes of Tregs and the quantitative relationship between interleukin (IL-10) concentration gradient and CD8⁺ T cell depletion are still unclear. In view of the above mechanisms, this paper reviews the strategies such as precise targeting of immunosuppressive cells and synergistic metabolic-immune intervention, and prospects the direction of multi-omics guided individualized treatment, which provides theoretical support for overcoming the dilemma of immunotherapy for CRLM.