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

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).