Hormonal and nutritional biomarkers in immune checkpoint inhibition for gastrointestinal cancers: a narrative review
- 1Department of Clinical Laboratory, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China
- 2Department of Transfusion, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China
Abstract
Immune checkpoint inhibitors (ICIs) have improved treatment outcomes in selected gastrointestinal cancers, although the efficacy and frequency of immune-related adverse events (irAEs) vary substantially. Established tumor biomarkers, particularly microsatellite instability-high/mismatch repair deficiency (MSI-H/dMMR), guide treatment selection, whereas the additional value of circulating hormonal and nutritional markers remains uncertain. In this narrative review, we have examined the prognostic relevance of glucocorticoids, thyroid and sex hormones, albumin, vitamin D, and trace elements in gastrointestinal cancers based on clinical evidence. Albumin-based indices have shown prognostic value in gastric cancer, whereas cortisol and composite host-state scores require independent prospective evaluation. Furthermore, treatment-emergent thyroiditis is a toxicity-associated event with possible pharmacodynamic implications and should not be conflated with pretreatment thyroid function. Vitamin D has context-dependent immunoregulatory effects, and observational or preclinical findings do not establish that supplementation improves the efficacy of ICIs against gastrointestinal tumors. The evidence for zinc is exploratory at present, and clinical evidence for selenium remains insufficient. Tumor metabolic reprogramming provides a mechanistic connection between nutrient availability and immune function, but circulating markers cannot be considered definitive indicators of intra-tumoral metabolism. Microbiota-derived metabolites provide a potential connection between nutrient availability, endocrine signaling, and immune function, although their contribution to clinical ICI benefit remains incompletely defined. These biomarkers may guide supportive assessment and research stratification, but do not justify withholding otherwise indicated ICI therapy, diagnosing resistance, or altering oncological surveillance. Clinical translation requires standardized assays, appropriate comparators, treatment–biomarker interaction testing, and validated models with demonstrated clinical utility.
The roles of hormonal and nutritional biomarkers in gastrointestinal cancer immunotherapy with ICIs. Hormones (GC, estrogen, androgen, T3/T4) modulate immune cells via PD-L1 regulation. Nutrients (albumin, vitamin D, trace elements) shape anti-tumor immunity and immunometabolism. Their interactions may contribute to heterogeneity in host status and treatment outcomes. Current clinical use centers on supportive assessment and toxicity monitoring; prognostic modeling and interventions intended to modify ICI efficacy require prospective validation.
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BibTeX
@article{luo2026hormonal,
title = {{Hormonal and nutritional biomarkers in immune checkpoint inhibition for gastrointestinal cancers: a narrative review}},
author = {Hao Luo and Han Wu and HaiYu Zhang},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1968875},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1968875/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Hormonal and nutritional biomarkers in immune checkpoint inhibition for gastrointestinal cancers: a narrative review
AU - Hao Luo
AU - Han Wu
AU - HaiYu Zhang
PY - 2026
DA - 2026/10/22
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1968875
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1968875/full
AB - Immune checkpoint inhibitors (ICIs) have improved treatment outcomes in selected gastrointestinal cancers, although the efficacy and frequency of immune-related adverse events (irAEs) vary substantially. Established tumor biomarkers, particularly microsatellite instability-high/mismatch repair deficiency (MSI-H/dMMR), guide treatment selection, whereas the additional value of circulating hormonal and nutritional markers remains uncertain. In this narrative review, we have examined the prognostic relevance of glucocorticoids, thyroid and sex hormones, albumin, vitamin D, and trace elements in gastrointestinal cancers based on clinical evidence. Albumin-based indices have shown prognostic value in gastric cancer, whereas cortisol and composite host-state scores require independent prospective evaluation. Furthermore, treatment-emergent thyroiditis is a toxicity-associated event with possible pharmacodynamic implications and should not be conflated with pretreatment thyroid function. Vitamin D has context-dependent immunoregulatory effects, and observational or preclinical findings do not establish that supplementation improves the efficacy of ICIs against gastrointestinal tumors. The evidence for zinc is exploratory at present, and clinical evidence for selenium remains insufficient. Tumor metabolic reprogramming provides a mechanistic connection between nutrient availability and immune function, but circulating markers cannot be considered definitive indicators of intra-tumoral metabolism. Microbiota-derived metabolites provide a potential connection between nutrient availability, endocrine signaling, and immune function, although their contribution to clinical ICI benefit remains incompletely defined. These biomarkers may guide supportive assessment and research stratification, but do not justify withholding otherwise indicated ICI therapy, diagnosing resistance, or altering oncological surveillance. Clinical translation requires standardized assays, appropriate comparators, treatment–biomarker interaction testing, and validated models with demonstrated clinical utility. The roles of hormonal and nutritional biomarkers in gastrointestinal cancer immunotherapy with ICIs. Hormones (GC, estrogen, androgen, T3/T4) modulate immune cells via PD-L1 regulation. Nutrients (albumin, vitamin D, trace elements) shape anti-tumor immunity and immunometabolism. Their interactions may contribute to heterogeneity in host status and treatment outcomes. Current clinical use centers on supportive assessment and toxicity monitoring; prognostic modeling and interventions intended to modify ICI efficacy require prospective validation.
SN - 1664-3224
ER -