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

Z Mei, Y Liu, C Liu, A Cui, Z Liang, G Wang, H Peng, L Cui, C Li, Z Mei, Y Liu, C Liu, A Cui, Z Liang, G Wang, H Peng, L Cui, C Li

Abstract

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.

Figures

Figure 1
Figure 1
Flowchart of the study selection.
Figure 2
Figure 2
Forest plots of the random-effect meta-analysis for the efficacy of tumour-infiltrating inflammatory cells for generalised tumour inflammatory infiltrate (A) and the CD3+ (B), CD8+ (C) and FoxP3+ (D) subsets stratified by infiltration location, including the tumour centre (CC), tumour stroma (ST) and invasive tumour margin (IM). The horizontal bars indicate the 95% CIs. The size of the square around each effect estimate indicates the weight of the individual study in the meta-analysis. Note: (A) Generalised tumour inflammatory infiltrate; (B1) CD3+ (CC); (B2) CD3+ (ST); (B3) CD3+ (IM); (C1) CD8+ (CC); (C2) CD8+ (ST); (C3) CD8+ (IM); (D1) FoxP3+ (CC); (D2) FoxP3+ (ST); (E) CCR7+.
Figure 2
Figure 2
Forest plots of the random-effect meta-analysis for the efficacy of tumour-infiltrating inflammatory cells for generalised tumour inflammatory infiltrate (A) and the CD3+ (B), CD8+ (C) and FoxP3+ (D) subsets stratified by infiltration location, including the tumour centre (CC), tumour stroma (ST) and invasive tumour margin (IM). The horizontal bars indicate the 95% CIs. The size of the square around each effect estimate indicates the weight of the individual study in the meta-analysis. Note: (A) Generalised tumour inflammatory infiltrate; (B1) CD3+ (CC); (B2) CD3+ (ST); (B3) CD3+ (IM); (C1) CD8+ (CC); (C2) CD8+ (ST); (C3) CD8+ (IM); (D1) FoxP3+ (CC); (D2) FoxP3+ (ST); (E) CCR7+.
Figure 3
Figure 3
Funnel plots of the relationship between the size of the effect in individual studies and the precision of the study estimate (log HR, horizontal axis; s.e., vertical axis) for generalised tumour inflammatory infiltrate (A) and T lymphocyte subgroups for OS (B).

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