SYSTEMATIC REVIEW article
Front. Oncol.
Sec. Gastrointestinal Cancers: Colorectal Cancer
This article is part of the Research TopicTumour Microenvironment: From Biomedical Research To Clinic UseView all articles
Tumor-Associated Neutrophils and Survival Outcomes in Colorectal Cancer: A Systematic Review and Multilevel Meta-Analysis
Provisionally accepted
- 1Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- 2Nanjing University of Chinese Medicine, Nanjing, China
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Objective: Tumor-associated neutrophils (TANs) are abundant in the colorectal cancer (CRC) microenvironment, but their prognostic relevance remains controversial. We conducted an updated systematic review and multilevel meta-analysis to evaluate associations between TAN infiltration in primary tumors and survival outcomes in CRC. Methods: PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to January 1, 2026. We included studies of histologically confirmed CRC that quantified TANs in primary tumors and reported hazard ratios (HRs) for cancer-specific survival (CSS), overall survival (OS), or disease-free survival (DFS); recurrence-free survival was combined with DFS. Multilevel random-effects models accounted for correlated effect sizes and generated overall and region-specific estimates from univariate and multivariate analyses. Prespecified subgroup analyses and multilevel meta-regression explored heterogeneity by study region, tumor stage, detection method, and TAN markers. Results: Twenty-five studies (10,356 patients) were included. High TAN infiltration was consistently associated with improved CSS (univariate HR 0.58, 95% CI 0.48–0.71; multivariate HR 0.66, 95% CI 0.54–0.81) with low heterogeneity across tumor regions. For OS and DFS, pooled estimates suggested an overall protective trend with substantial heterogeneity; subgroup analyses indicated stronger protective associations in Euro–American cohorts and in stage I–III disease. In contrast, multivariate DFS models suggested higher recurrence risk in Euro–American populations and in studies with unclear TAN marker reporting. Meta-regression identified tumor stage and TAN markers as major contributors to heterogeneity in OS and DFS. Conclusions: High TAN infiltration is a robust, independent favorable factor for cancer-specific survival in CRC. Associations with OS and DFS are context-dependent and appear modified by tumor stage and methodological factors, particularly TAN markers and detection methods, supporting refined prognostic stratification and further study of neutrophil-targeted strategies.
Keywords: Cancer-specific survival, colorectal cancer, Disease-Free Survival, Meta-analysis, Overallsurvival, Tumor Microenvironment, Tumor-associated neutrophils
Received: 22 Jan 2026; Accepted: 09 Feb 2026.
Copyright: © 2026 Yang, Zhu, Zhao and Tian. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yun Tian
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.