Prognostic value of the systemic immune-inflammation index in gastrointestinal cancers treated with immune checkpoint inhibitors - a systematic review and meta-analysis

Sep 22, 2026

Elevated gastrointestinal cancer mortality persists despite immune checkpoint inhibitor (ICI) advances, prompting the need for dependable biomarkers. This systematic review evaluates the prognostic relevance of the systemic immune-inflammation index (SII), formed from platelet, neutrophil, and lymphocyte counts, in patients receiving ICIs. Using PRISMA-guided evidence from Cochrane Library, Embase, and PubMed (through August 15, 2025), pooled results assess survival endpoints including progression-free survival and overall survival.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages17

Reading Time43 min

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Abstract

Background

Methods

Results

Conclusion

Introduction

Immune checkpoint inhibitors and treatment variability

Systemic immune-inflammation index (SII) as a biomarker

Lu et al. BMCGastroenterology (2026) 26:550 BMC Gastroenterology [https://doi.org/10.1186/s12876-026-05014-x](https://doi.org/10.1186/s12876-026-05014-x) SYSTEMATIC REVIEW Open Access Prognostic value of the systemic immune- inflammation index in gastrointestinal cancers treated with immune checkpoint inhibitors: a systematic review and meta-analysis Jiamin Lu1, Yuqian Feng1, Kaibo Guo2 and Hong Pan 1* Abstract Background Gastrointestinal (GI) cancers, including pancreatic, gastric, esophageal, colorectal, and hepatocellular carcinoma (HCC), have high mortality rates. Despite advances in immune checkpoint inhibitors (ICIs), treatment outcomes remain variable. Identifying reliable biomarkers, such as the systemic immune-inflammation index (SII), which combines platelet, neutrophil, and lymphocyte counts, could help optimize treatment strategies. Biologically, an elevated SII is thought to indicate a dominance of pro-tumor inflammation and a suppressed adaptive immune response, thereby potentially dampening the therapeutic efficacy of ICIs. Methods A systematic review was conducted of studies from Cochrane Library, Embase, and PubMed, published until August 15, 2025. This review was conducted in strict adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligible studies involved GI cancer patients treated with ICIs, reported baseline or treatment SII data, and provided hazard ratios (HRs) for progression-free survival (PFS) or overall survival (OS) . Exclusions included studies on non-GI cancers or incomplete data. Results 28 studies with 4752 patients were included. High baseline SII levels were associated with worse OS and PFS in gastric cancer (OS: HR = 2 . 24, 95% CI: 1 .84–2. 72, I2 = 19 .4%; PFS: HR = 1 . 57, 95% CI: 1 .35–1. 83, I2 = 0%), HCC (OS: HR = 1 . 80, 95% CI: 1 .47–2. 21, I2 = 2 . 6%; PFS: HR = 1 . 60, 95% CI: 1 .24–2. 06, I2 = 53 . 7%), and esophageal cancer (OS: HR = 1 . 79, 95% CI: 1 .53–2. 09, I2 = 39 . 8%; PFS: HR = 1 . 50, 95% CI: 1 .12–2. 01, I2 = 32 . 6%) . Baseline SII was a stronger predictor of survival than post-treatment or dynamic measurements. Conclusion SII is a promising, cost-effective prognostic biomarker for GI cancer patients receiving ICIs. Elevated baseline SII predicts poorer survival, particularly in gastric cancer, HCC, and esophageal cancer. These findings highlight the potential utility of SII in patient risk stratification and clinical decision-making, thereby supporting its integration into precision oncology strategies. Keywords Systemic immune-inflammation index, Gastrointestinal cancer, Immune checkpoint inhibitors, Prognosis, Meta-analysis, Overall survival. *Correspondence: Hong Pan [panhong_0707@163.com](panhong_0707@163.com) 1The First Affiliated Hospital of Zhejiang Chinese Medical University, Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang 310003, China 2Affiliated Hangzhou First People’s Hospital, School of medicine, Westlake University, Hangzhou 310024, China © The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission direct

FAQs

What is the systemic immune-inflammation index (SII) and why is it studied in ICI-treated GI cancers?

SII is a blood-based biomarker combining platelet, neutrophil, and lymphocyte counts. It is studied because higher SII may reflect pro-tumor inflammation and weakened adaptive immune response, potentially reducing ICI effectiveness.

How were the studies selected for the systematic review and meta-analysis?

Studies were searched in Cochrane Library, Embase, and PubMed up to August 15, 2025. Eligible studies involved GI cancer patients treated with ICIs and reported baseline or treatment SII data with hazard ratios for progression-free survival or overall survival.

What do the pooled findings indicate about baseline SII and patient survival?

High baseline SII was associated with worse overall survival and progression-free survival in gastric cancer, hepatocellular carcinoma, and esophageal cancer. Baseline SII also appeared stronger than post-treatment or dynamic SII measurements for predicting survival.

Sep 22, 2026

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