Integrative pan-cancer and clinical cytokine profiling reveals a pro-inflammatory cytokine index for colon cancer peritoneal metastasis and immunotherapy response
4 affiliations
- 1Center for Precision Cancer Medicine & Translational Research, Tianjin Cancer Hospital Airport Hospital
- 2Pathology Department, Tianjin Cancer Hospital Airport Hospital
- 3Department of Technology Transfer, Tianjin Cancer Hospital Airport Hospital
- 4Center for Precision Oncology Testing and Translational Research, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin’s Clinical Research Center for Cancer
Abstract
Background: Cytokines are central to tumor immunity, yet their landscape and clinical utility across cancer types remain incompletely characterized.
Methods: We selected a representative cytokine panel covering Th1/Th2/Th17, pro-inflammatory, regulatory, and chemokine functions. Using TCGA pan-cancer data, we derived a transcriptomic cytokine index (gCCI) as the difference between pro-tumor and anti-tumor ssGSEA scores and evaluated its associations with prognosis, immune microenvironment, and immunotherapy response. We further validated a protein-level cytokine index (pCCI) using the same formula in an independent cohort of 183 cytokine profiling assays from colorectal cancer patients.
Results: The gCCI effectively distinguished tumor from normal tissue in colorectal cancer and stratified survival in multiple cancer types. High gCCI was associated with activated inflammatory pathways by GSEA and showed cancer-type-specific correlations with MSI, TMB, and immune cell infiltration. Notably, low gCCI correlated with better immunotherapy response and prolonged survival in two independent cohorts. In protein-level validation, pCCI was significantly associated with T stage, N stage, M stage, and tumor location (all p < 0.05), with M1c (peritoneal metastasis) showing the highest pCCI levels among M substages. Dichotomized analysis by median pCCI further revealed that high pCCI was significantly enriched in colon cancer patients with M1c, whereas no such associations were observed in rectal cancer.
Conclusions: The cytokine index, at both transcriptomic and protein levels, is associated with prognosis and immunotherapy response, with its utility being cancer-type and site-specific. Its particular relevance to colon cancer and peritoneal metastasis warrants further validation in prospective studies.
Related
- Integrative in vitro, in vivo, and in silico investigation with mineral profiling of Combretum indicum: A multi-target therapeutic candidate exhibiting antioxidant, thrombolytic, anti-inflammatory, anti-arthritic, analgesic, cytotoxic, and anthelmintic activities
- Intraperitoneal and Intravenous Paclitaxel Plus S-1 for Gastric Cancer With Peritoneal Metastasis
- Multi-omics reveals tumor microenvironment heterogeneity and therapeutic vulnerabilities in peritoneal metastasis of gastric cancer
- Surgical Impact on Postoperative Morbidity in Colorectal Cancer with Peritoneal Metastasis: A Multicenter Prospective Observational Study.
- Gastric cancer peritoneal metastases as an immune compartment: immune evasion, systemic immunotherapy and regional treatment strategies
BibTeX
@article{wu2026integrative,
title = {{Integrative pan-cancer and clinical cytokine profiling reveals a pro-inflammatory cytokine index for colon cancer peritoneal metastasis and immunotherapy response}},
author = {Caihong Wu and Xin Li and Dan Wang and Dongmei Han and Hao Jin and Weishuai Liu},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1977517},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1977517/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Integrative pan-cancer and clinical cytokine profiling reveals a pro-inflammatory cytokine index for colon cancer peritoneal metastasis and immunotherapy response
AU - Caihong Wu
AU - Xin Li
AU - Dan Wang
AU - Dongmei Han
AU - Hao Jin
AU - Weishuai Liu
PY - 2026
DA - 2026/10/26
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1977517
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1977517/full
AB - Background: Cytokines are central to tumor immunity, yet their landscape and clinical utility across cancer types remain incompletely characterized. Methods: We selected a representative cytokine panel covering Th1/Th2/Th17, pro-inflammatory, regulatory, and chemokine functions. Using TCGA pan-cancer data, we derived a transcriptomic cytokine index (gCCI) as the difference between pro-tumor and anti-tumor ssGSEA scores and evaluated its associations with prognosis, immune microenvironment, and immunotherapy response. We further validated a protein-level cytokine index (pCCI) using the same formula in an independent cohort of 183 cytokine profiling assays from colorectal cancer patients. Results: The gCCI effectively distinguished tumor from normal tissue in colorectal cancer and stratified survival in multiple cancer types. High gCCI was associated with activated inflammatory pathways by GSEA and showed cancer-type-specific correlations with MSI, TMB, and immune cell infiltration. Notably, low gCCI correlated with better immunotherapy response and prolonged survival in two independent cohorts. In protein-level validation, pCCI was significantly associated with T stage, N stage, M stage, and tumor location (all p < 0.05), with M1c (peritoneal metastasis) showing the highest pCCI levels among M substages. Dichotomized analysis by median pCCI further revealed that high pCCI was significantly enriched in colon cancer patients with M1c, whereas no such associations were observed in rectal cancer. Conclusions: The cytokine index, at both transcriptomic and protein levels, is associated with prognosis and immunotherapy response, with its utility being cancer-type and site-specific. Its particular relevance to colon cancer and peritoneal metastasis warrants further validation in prospective studies.
SN - 1664-3224
ER -