Impact of TGF-β1 on tumor immune microenvironment and prognosis in colorectal liver oligometastasis

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BACKGROUND: Colorectal liver oligometastasis (CLO) represents an intermediate state between localized and widely disseminated disease. Transforming growth factor-beta 1 (TGF-β1) plays a stage-dependent role in the tumorigenesis of colorectal cancer. However, its prognostic value and impact on the immune microenvironment in CLO remain poorly understood. METHODS: We retrospectively analyzed 95 CLO patients who underwent curative resection of primary tumors and liver metastases. TGF-β1 expression was assessed by immunohistochemistry (IHC) in matched tumor and liver metastasis samples. Multiplex IHC and multispectral imaging were used to quantify CD3⁺, CD8⁺, and Foxp3⁺ T-cell infiltration in intratumoral and peritumoral compartments. Survival outcomes were compared using Kaplan-Meier analysis and Cox proportional hazards model. Associations with immune infiltration were subsequently validated through the analysis of TCGA colon adenocarcinoma datasets utilizing the TIMER2.0 platform. RESULTS: The median IHC score for both primary tumors and liver metastases was 6. The consistency rate of TGF-β1 expression in primary tumors and liver metastases was 70 %. High TGF-β1 expression (≥6) in liver oligometastases was independently associated with poorer recurrence-free survival (RFS; HR = 3.689, 95 % CI: 1.799-7.567, P < 0.001) and overall survival (OS; HR = 3.131, 95 % CI: 1.278-7.669, P = 0.013). Patients with consistently high TGF-β1 expression in the primary tumors and liver metastases were associated with the poorest prognosis (P < 0.001). High TGF-β1 expression was associated with significantly reduced intratumoral CD3⁺ and CD8⁺ T cell infiltration and increased Foxp3⁺ regulatory T cell density (P < 0.05). This association was also observed in the cohort from TCGA. CONCLUSION: High TGF-β1 expression in CLO is associated with poor prognosis and an immunosuppressive microenvironment.