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

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.