Tumour-infiltrating inflammation and prognosis in colorectal cancer: systematic review and meta-analysis

Background: The role of tumour-infiltrating inflammation in the prognosis of patients with colorectal cancer (CRC) has not been fully evaluated. The primary objective of our meta-analysis was to determine the impact of tumour-infiltrating inflammation on survival outcomes. Methods: Ovid MEDLINE and EMBASE were searched to identify studies reporting the prognostic significance of tumour-infiltrating inflammation for patients with CRC. The primary outcome measures were overall survival (OS), cancer-specific survival (CS) and disease-free survival (DFS). Results: A total of 30 studies involving 2988 patients were identified. Studies were subdivided into those considering the associations between CRC survival and generalised tumour inflammatory infiltrate (n = 12) and T lymphocyte subsets (n = 18). Pooled analyses revealed that high generalised tumour inflammatory infiltrate was associated with good OS (HR, 0.59; 95% CI, 0.48-0.72), CS (HR, 0.40; 95% CI, 0.27-0.61) and DFS (HR, 0.72; 95% CI, 0.57-0.91). Stratification by location and T lymphocyte subset indicated that in the tumour centre, CD3(+), CD8(+) and FoxP3(+) infiltrates were not statistically significant prognostic markers for OS or CS. In the tumour stroma, high CD8(+), but not CD3(+) or FoxP3(+) cell infiltrates indicated increased OS. Furthermore, high CD3(+) cell infiltrate was detected at the invasive tumour margin in patients with good OS and DFS; and high CCR7(+) infiltrate was also indicated increased OS. Conclusion: Overall, high generalised tumour inflammatory infiltrate could be a good prognostic marker for CRC. However, significant heterogeneity and an insufficient number of studies underscore the need for further prospective studies on subsets of T lymphocytes to increase the robustness of the analyses.