Abstract
Background: A comprehensive investigation into immune cell infiltration provides more accurate and reliable prognostic information for patients with colorectal liver oligometastases (CLO) after liver metastasectomy. Methods: Simultaneous detection of the immune constituents CD3+, CD8+, Foxp3+ T, and α-SMA+ cells in the liver oligometastasis of 133 patients was conducted using a four-colour immunohistochemical multiplex technique. Immune cells were quantified, and tumour-infiltrating lymphocyte (TIL) ratios were subsequently calculated. Correlation analysis was performed using Pearson’s correlation. Recurrence-free survival (RFS) and overall survival (OS) for TIL ratios were analysed using the Kaplan–Meier method and Cox regression models. Results: Significantly fewer CD3+, CD8+, and Foxp3+ T cells were observed in the intratumoural region than in the peritumoural region of liver metastases. CD3+, CD8+, Foxp3+ T, and α-SMA+ cells showed significantly positive correlations with each other both in the intratumoural and peritumoural regions of liver metastases. Only the CD8/CD3 TIL ratio demonstrated a positive correlation between intratumoural and peritumoural regions of liver metastases (r = 0.541, p < 0.001). Patients with high intratumoural CD8/CD3 ratios had significantly longer 3-year RFS (59.0% vs. 47.4%, p = 0.035) and 3-year OS rates (83.3% vs. 65.8%, p = 0.007) than those with low intratumoural CD8/CD3 ratios. Multivariate analyses revealed that the intratumoural CD8/CD3 ratio was independently associated with RFS (HR = 0.593; 95% CI = 0.357–0.985; p = 0.043) and OS (HR = 0.391; 95% CI = 0.193–0.794; p = 0.009). Conclusion: These findings offer a better understanding of the prognostic value of immune cell infiltration on liver oligometastasis from colorectal cancer.
Highlights
Distant metastasis remains a leading cause of treatment failure and disease-related death for colorectal cancer patients [1]
These findings suggest a role for CD3+ T cells in activating an immune response in colorectal liver metastases (CRLM), especially cytotoxic CD8+ T cells, which could act as direct mediators of tumour killing and enhanced activation status of tumour-infiltrating lymphocyte (TIL)
We found that the number of infiltrating Tregs was not a significant determinant of colorectal liver oligometastases (CLO), presenting a lower tumour burden than the more advanced CRLM, and showing relatively low α-smooth muscle actin (α-SMA)-labelled Cancer-associated fibroblasts (CAFs) were found to be an abundant stromal immune cell population within the liver oligometastasis microenvironment, and they act as suppressive intermediates in the tumour microenvironment (TME) through the secretion of immunomodulatory factors, subsequently regulating tumour invasion and stimulating metastasis [30,31]
Summary
Distant metastasis remains a leading cause of treatment failure and disease-related death for colorectal cancer patients [1]. High densities of CD3+ , CD8+ , and Foxp3+ T cells were associated with prolonged survival and a significant therapeutic response in CRC patients [11,12,13,14]. Cancer-associated fibroblasts (CAFs) are another abundant cell type in the tumour immune microenvironment and can be identified by markers such as α-smooth muscle actin (α-SMA) [16]. A comprehensive investigation into immune cell infiltration provides more accurate and reliable prognostic information for patients with colorectal liver oligometastases (CLO). CD3+ , CD8+ , Foxp3+ T, and α-SMA+ cells showed significantly positive correlations with each other both in the intratumoural and peritumoural regions of liver metastases. The CD8/CD3 TIL ratio demonstrated a positive correlation between intratumoural and peritumoural regions of liver metastases (r = 0.541, p < 0.001).
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