Objective Colorectal cancer liver metastasis (CRLM) is a leading cause of mortality in patients with colorectal cancer (CRC). Although local immunity centered on CD8⁺ T cells plays a critical role in suppressing tumor progression, the unique immunotolerant microenvironment of liver metastases often induces heterogeneous functional alterations in these cells. However, the lineage trajectory and molecular mechanisms underlying phenotypic remodeling of specific CD8⁺ tissue-resident memory T cells during CRLM progression remain incompletely understood. Therefore, this study aimed to investigate the lineage evolution and phenotypic remodeling characteristics of specific CD8⁺ tissue-resident memory T cells in the CRLM microenvironment, explore their potential communication with microenvironmental cells, and establish a clinical prediction and molecular subtyping strategy based on the perturbation profile of this cell subset.Methods This study integrated three single-cell RNA sequencing (scRNA-seq) datasets of CRC, spanning normal tissue, polyps, primary tumors, and liver metastases. Tissue preference analysis, T-cell state scoring, trajectory inference, and transcriptional regulatory analysis were performed to identify and characterize key CRLM-associated cell subsets. CellChat and MultiNicheNet were further employed to investigate intercellular communication and potential ligand-receptor interactions. Subsequently, differentially expressed genes of the identified subset were used to construct a gene interaction perturbation network in the cancer genome atlas (TCGA) cohort, followed by consensus clustering for molecular subtyping and independent validation in a gene expression omnibus (GEO) cohort. Finally, immunotherapy response and drug sensitivity analyses were performed to evaluate differences in immune microenvironmental characteristics and potential therapeutic responses among molecular subtypes.Results Single-cell analysis successfully identified a key CRLM-associated KLRB1⁺ CD8⁺ tissue-resident memory T-cell subset (CD8-Trm-KLRB1), which exhibited prominent tissue-resident and immunoregulatory features, together with relatively low cytotoxic activity. Pseudotime analysis suggested that CD8⁺ T cells may undergo a continuous state transition from GZMB⁺ CD8⁺ effector T cells (CD8-Teff-GZMB), through GZMK⁺ CD8⁺ effector memory T cells (CD8-Tem-GZMK), to CD8-Trm-KLRB1 cells, accompanied by stress-related functional remodeling. Antigen presentation and T-cell receptor activity analyses suggested that this state transition was not simply attributable to insufficient antigen presentation or complete loss of T-cell receptor signaling. Cell-cell communication analysis indicated enhanced potential immunoregulatory communication between neutrophils and CD8-Trm-KLRB1 cells in the CRLM microenvironment, with the resistin (RETN)-adenylyl cyclase-associated protein 1 (CAP1)-mediated RETN-CAP1 ligand-receptor interaction being particularly prominent. Meanwhile, the CD48 molecule (CD48)-programmed cell death 1 (PDCD1)-mediated CD48-PDCD1 ligand-receptor interaction associated with CD8-Trm-KLRB1 cells also showed an increasing trend. The clinical molecular subtypes (subtype 1 and subtype 2) established based on the characteristics of this cell subset showed high consistency across TCGA and GEO cohorts. Subtype 2, which was associated with poorer prognosis, exhibited higher tumor immune dysfunction and exclusion (TIDE) scores and stronger immune exclusion features, while also showing a lower half-maximal inhibitory concentration (IC50) for axitinib, suggesting greater potential sensitivity to anti-angiogenic agents and a possible greater clinical benefit from such treatment.Conclusion This study reveals dynamic functional remodeling of CD8-Trm-KLRB1 cells during CRLM progression and suggests that their state may be regulated by upstream signals from the metastatic microenvironment, including neutrophil-associated RETN-CAP1 signaling, while their interactions with downstream immune cells through immunoregulatory communication such as CD48-PDCD1 may contribute to local immune microenvironmental remodeling. The molecular subtyping framework based on the perturbation characteristics of CD8-Trm-KLRB1-associated genes stratifies patients according to distinct prognostic and immune microenvironmental features and suggests potential differences in therapeutic response, providing a new perspective for understanding the CRLM microenvironment and developing individualized treatment strategies.