Tumour-Associated Neutrophils in Colorectal Cancer: a Systematic Review, Meta-analysis, and Comprehensive Literature Review

Clinical Snapshot

Key Findings

• P Value: Not explicitly reported in abstract; IM analyses cross significance threshold; TC analyses do not

• Effect Size: IM high TANs vs low TANs: OS HR=0.64 (favours high TANs); TC high TANs vs low TANs: OS HR=0.82 (non-significant). DFS: IM HR=0.47 (significant); TC HR=0.48 (non-significant)

• Primary Outcome: Overall survival (OS) stratified by TAN density at invasive margin (IM) and tumour core (TC)

• Nnt Or Sensitivity: Hazard ratios used (prognostic study design). IM-TAN HR=0.64 for OS represents a 36% relative reduction in hazard of death associated with high IM-TAN density. NNT not calculable from available data without baseline event rates.

• Confidence Interval: IM OS: 95% CI 0.50–0.81; IM DFS: 95% CI 0.25–0.88; TC OS: 95% CI 0.61–1.10; TC DFS: 95% CI 0.21–1.07

Clinical Application

TAN quantification by IHC is technically feasible in most tertiary pathology laboratories using standard neutrophil markers (e.g., CD66b, MPO). However, the absence of standardised thresholds, antibody panels, and scoring systems currently prevents routine clinical implementation. Integration into existing pathological reporting workflows would require prospective validation and consensus methodology. In Australia, colorectal cancer is the second most common cancer, with approximately 15,500 new cases diagnosed annually (AIHW). Pathological assessment of CRC resection specimens is standard practice under RCPA guidelines. TAN quantification is not currently part of routine pathological reporting or RACGP/COSA clinical guidelines for CRC. No PBS-listed biomarker test exists for TAN assessment. The findings from this meta-analysis are hypothesis-generating and would need prospective validation in Australian cohorts before informing TGA-regulated diagnostic test development or RACGP guideline updates. The results are relevant to Australian oncologists and gastroenterologists considering the tumour immune microenvironment in CRC prognostication, particularly in the context of emerging immunotherapy trials (e.g., pembrolizumab for MSI-H CRC on PBS). Adult patients with resected colorectal cancer stages I–IV undergoing pathological assessment. Most applicable to patients with accessible tumour tissue for IHC or HE-based TAN quantification at the invasive margin.

Abstract

PURPOSE: Neutrophils are at the forefront of innate immune response. The prognostic impact of tumour-associated neutrophils (TANs) remains unclear. This study aimed to evaluate the prognostic role of TANs in colorectal cancer (CRC). METHODS: A systematic review and meta-analysis were conducted using PubMed, Embase, and Scopus to identify studies correlating TANs with time-to-event survival analysis in patients with stages I-IV CRC from the date of inception until April 2024. Articles were included if they involved the identification of TANs through hematoxylin-eosin (HE) or immunohistochemistry (IHC) and reported survival analysis. Data was collected from the tumour core (TC) and invasive margin (IM). The hazard ratios (HRs) were extracted from the study results. Heterogeneity was evaluated using Cochran's Q and I². Primary and secondary endpoints were overall survival (OS) and disease-free survival (DFS). RESULTS: Of 4,292 citations found, 18 studies fulfilled eligibility criteria, encompassing 7,406 patients. IHC was used to identify TANs in 12 trials, while six performed HE. Five studies included patients with disease stages I-III, and 13 had stages I-IV. High TANs at the IM were associated with improved OS (HR = 0.64, 95% Confidence Interval [CI] 0.50-0.81, I2 = 48%) and DFS (HR = 0.47, 95% CI 0.25-0.88, I2 = 32%). At the TC, high TANs showed a trend towards better OS (HR = 0.82, 95% CI 0.61-1.10, I2 = 83%) and DFS (HR = 0.48, 95% CI 0.21-1.07, I2 = 93%), although not statistically significant and with high heterogeneity. CONCLUSION: In this systematic review and meta-analysis, high TANs at the invasive margin (IM), the tumour-host interface, was associated with improved prognosis in CRC. In contrast, no statistically significant association was observed for high TANs at the tumour core (TC).

References

1. 1.Abrahao, A. B. K., Felismino, T. C., & Kerr, D. (2026). Tumour-associated neutrophils in colorectal cancer: A systematic review, meta-analysis, and comprehensive literature review. Journal of Gastrointestinal Cancer. https://doi.org/10.1146/annurev-immunol-110519-071134