High tumour-associated neutrophils at the invasive margin are associated with improved overall survivalNeutrophils at Tumor Edge Linked to Better Colon Cancer Survival

This meta-analysis evaluated the prognostic implications of tumour-associated neutrophils (TANs) in patients diagnosed with stages I-IV colorectal cancer (CRC). The study included a total sample size of 7,406 patients. The analysis specifically examined the location of these cells—distinguishing between those located at the invasive margin (IM) and those within the tumour core (TC)—to determine their impact on patient outcomes.

The primary outcome measured was overall survival (OS). For patients with high TANs at the invasive margin (IM), the study reported a statistically significant association with improved OS, yielding an HR of 0.64 (95% CI 0.50-0.81, I^2 = 48%). In contrast, for patients with high TANs at the tumour core (TC), there was a trend toward better OS, but the results were not statistically significant, with an HR of 0.82 (95% CI 0.61-1.10, I^2 = 83%).

Secondary outcomes included disease-free survival (DFS). Similar to the primary outcome, high TANs at the invasive margin were associated with improved DFS, reporting an HR of 0.47 (95% CI 0.25-0.88, I^2 = 32%). For patients with high TANs at the tumour core, there was a trend toward better DFS, but this did not reach statistical significance, with an HR of 0.48 (95% CI 0.21-1.07, I^2 = 93%).

Safety and tolerability data were not reported in the study as it was a meta-analysis of observational outcomes rather than a clinical trial involving intervention administration. The analysis highlights a distinct difference in prognostic value based on the anatomical location of the neutrophils within the tumor microenvironment.

Methodologically, the study noted high heterogeneity at the tumour core (TC) for both OS and DFS metrics. This suggests that while the invasive margin provides a clearer signal for prognosis, the data regarding the tumour core are less consistent across the included studies.

These findings suggest that the location of neutrophils within the tumor microenvironment may be a relevant prognostic indicator in colorectal cancer. Specifically, high TANs at the invasive margin correlate with improved survival outcomes, whereas results for the tumour core were not statistically significant. This distinction may help clinicians better interpret the role of the immune microenvironment in CRC.

Several questions remain regarding the biological mechanisms driving these differences between the invasive margin and the tumour core. Furthermore, while the association is clear at the invasive margin, more data are needed to determine if this finding holds across diverse subtypes of colorectal cancer or different staging protocols.