{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T20:54:32Z","timestamp":1792616072873,"version":"4.5.0"},"reference-count":143,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, yet durable benefit remains limited to selected patients. Established biomarkers, including PD-L1 expression, tumor mutational burden, and microsatellite instability, remain predominantly tumor-centered and incompletely capture inter-individual variability. In this Perspective, we highlight systemic host physiology as an underappreciated determinant of the tumor microenvironment, ICI efficacy, and immune-related toxicity. We discuss how the hypothalamic\u2013pituitary\u2013adrenal axis, thyroid function, insulin signaling, nutritional status, micronutrients such as vitamin D and iron, emerging metabolic modulators, body composition, and the gut microbiome may influence T-cell activation, exhaustion, and myeloid-cell function. We also examine unresolved controversies, including the obesity paradox, the potential risk of GLP-1 receptor agonist-associated sarcopenia, and the lack of standardized biomarker thresholds and sampling protocols. To facilitate clinical translation, we outline a conceptual, hypothesis-generating spatiotemporal management framework integrating pre-treatment host profiling, peri-treatment metabolic and nutritional modulation, and post-treatment dynamic monitoring. Composite indices such as the Prognostic Immune and Nutritional Index, together with precise body-composition assessment, may improve risk stratification. However, host-directed interventions should be interpreted cautiously because current evidence remains heterogeneous and largely observational or preclinical. Prospective, multidisciplinary studies are required to validate these concepts and determine whether host-directed strategies can improve ICI efficacy while limiting immune-related toxicity.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1857147","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T04:24:35Z","timestamp":1786595075000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["The role of hormonal and nutritional biomarkers in predicting immune checkpoint inhibitor efficacy: current limitations and future prospects"],"prefix":"10.3389","volume":"17","author":[{"given":"Ruichen","family":"Yuan","sequence":"first","affiliation":[{"name":"College of Integrative Chinese and Western Medicine, Changchun University of Chinese Medicine","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuejiao","family":"Lan","sequence":"additional","affiliation":[{"name":"Precision Molecular Medicine Center, Jilin Province People\u2019s Hospital","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingda","family":"Wu","sequence":"additional","affiliation":[{"name":"Precision Molecular Medicine Center, Jilin Province People\u2019s Hospital","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodan","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Integrative Chinese and Western Medicine, Changchun University of Chinese Medicine","place":["Changchun, Jilin, China"]},{"name":"Precision Molecular Medicine Center, Jilin Province People\u2019s Hospital","place":["Changchun, Jilin, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(25)01635-6","article-title":"The global, regional, and national burden of cancer, 1990-2023, with forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2023","volume":"406","year":"2025","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"3801","DOI":"10.1038\/s41467-020-17670-y","article-title":"A decade of immune-checkpoint inhibitors in cancer therapy","volume":"11","author":"Robert","year":"2020","journal-title":"Nat Commun"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.4110\/in.2022.22.e2","article-title":"Immune checkpoint inhibitors in 10 years: Contribution of basic research and clinical application in cancer immunotherapy","volume":"22","author":"Lee","year":"2022","journal-title":"Immune Netw"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3390\/jcm14186680","article-title":"Immune checkpoint inhibitors beyond progression in various solid tumors: A systematic review and pooled analysis","volume":"14","author":"Petrelli","year":"2025","journal-title":"J Clin Med"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.2217\/imt-2021-0119","article-title":"Sargramostim and immune checkpoint inhibitors: combinatorial therapeutic studies in metastatic melanoma","volume":"13","author":"Tarhini","year":"2021","journal-title":"Immunotherapy"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/curroncol29050247","article-title":"Immune checkpoint inhibitors in cancer therapy","volume":"29","author":"Shiravand","year":"2022","journal-title":"Curr Oncol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-021-00473-5","article-title":"PD-L1 as a biomarker of response to immune-checkpoint inhibitors","volume":"18","author":"Doroshow","year":"2021","journal-title":"Nat Rev Clin Oncol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s12943-024-02212-7","article-title":"Resistance mechanisms to immune checkpoint inhibitors: updated insights","volume":"24","author":"Alsaafeen","year":"2025","journal-title":"Mol Cancer"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.3923","article-title":"Fatal toxic effects associated with immune checkpoint inhibitors: A systematic review and meta-analysis","volume":"4","author":"Wang","year":"2018","journal-title":"JAMA Oncol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/s41379-020-00664-y","article-title":"A pan-cancer analysis of PD-L1 immunohistochemistry and gene amplification, tumor mutation burden and microsatellite instability in 48,782 cases","volume":"34","author":"Huang","year":"2021","journal-title":"Mod Pathol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s13073-017-0424-2","article-title":"Analysis of 100,000 human cancer genomes reveals the landscape of tumor mutational burden","volume":"9","author":"Chalmers","year":"2017","journal-title":"Genome Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1186\/s40364-020-00209-0","article-title":"Predictive biomarkers for cancer immunotherapy with immune checkpoint inhibitors","volume":"8","author":"Bai","year":"2020","journal-title":"biomark Res"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2025.1753660","article-title":"Pre-treatment endocrine-nutritional signatures predict clinical benefit from PD-1\/PD-L1 blockade in hematologic Malignancies","volume":"12","author":"Huang","year":"2026","journal-title":"Front Nutr"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-024-02929-4","article-title":"Association between pretreatment emotional distress and immune checkpoint inhibitor response in non-small-cell lung cancer","volume":"30","author":"Zeng","year":"2024","journal-title":"Nat Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2024.1120","article-title":"Body composition in advanced non-small cell lung cancer treated with immunotherapy","volume":"10","author":"Chaunzwa","year":"2024","journal-title":"JAMA Oncol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023022928","article-title":"Procoagulant platelets promote immune evasion in triple-negative breast cancer","volume":"144","author":"Schaubaecher","year":"2024","journal-title":"Blood"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.joim.2024.06.004","article-title":"Effects of acupuncture on hypothalamic-pituitary-adrenal axis: Current status and future perspectives","volume":"22","author":"Zheng","year":"2024","journal-title":"J Integr Med"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1568828","article-title":"Interplay between endogenous hormones and immune systems in human metapneumovirus pathogenesis and management","volume":"16","author":"Ruiz-Pozo","year":"2025","journal-title":"Front Pharmacol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2012.07.022","article-title":"Cortisol and inflammatory processes in ovarian cancer patients following primary treatment: relationships with depression, fatigue, and disability","author":"Schrepf","year":"2013","journal-title":"Brain Behav Immun"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1097\/psy.0b013e318186fb27","article-title":"Stress management intervention reduces serum cortisol and increases relaxation during treatment for nonmetastatic breast cancer","volume":"70","author":"Phillips","year":"2008","journal-title":"Psychosom Med"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41435-023-00194-y","article-title":"Human lung carcinomas synthesize immunoregulatory glucocorticoids","volume":"24","author":"Merk","year":"2023","journal-title":"Genes Immun"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1172\/jci173141","article-title":"Tumors recycle glucocorticoids to drive Treg-mediated immunosuppression","volume":"133","author":"Swatler","year":"2023","journal-title":"J Clin Invest"},{"key":"B23","doi-asserted-by":"publisher","first-page":"504","DOI":"10.1038\/s41419-025-07810-x","article-title":"Therapeutic targeting of FOSL1 and RELA-dependent transcriptional mechanisms to suppress pancreatic cancer metastasis","volume":"16","author":"Aggrey-Fynn","year":"2025","journal-title":"Cell Death Dis"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.119486","article-title":"Disruption of the Clock Component BMAL1 in HDM-induced asthma causes GC resistance in airway epithelial cells by regulating GR phosphorylation through the DUSP4-p38MAPK pathway","volume":"21","author":"Huang","year":"2025","journal-title":"Int J Biol Sci"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/416194a","article-title":"RICK\/Rip2\/CARDIAK mediates signalling for receptors of the innate and adaptive immune systems","volume":"416","author":"Kobayashi","year":"2002","journal-title":"Nature"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1084\/jem.193.7.803","article-title":"Glucocorticoids attenuate T cell receptor signaling","volume":"193","author":"Van Laethem","year":"2001","journal-title":"J Exp Med"},{"key":"B27","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1111\/imm.70028","article-title":"Exercise duration modulates cortisol release and chronic cortisol exposure jeopardises T cell effector functions","volume":"177","author":"Luu","year":"2026","journal-title":"Immunology"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1080\/2162402x.2026.2643494","article-title":"Prednisolone modulates CD8(+) and regulatory T-cell activity to dampen response to immune checkpoint inhibitor therapy in melanoma","volume":"15","author":"Brown","year":"2026","journal-title":"Oncoimmunology"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2024.1429912","article-title":"Systemic immunostimulation induces glucocorticoid-mediated thymic involution succeeded by rebound hyperplasia which is impaired in aged recipients","volume":"15","author":"Collins","year":"2024","journal-title":"Front Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1002\/eji.70033","article-title":"The mitigating effect of combined glucocorticoids with immune checkpoint inhibitors on lymphocyte activation gene-3 and programmed death-1 expression","volume":"55","author":"Gertel","year":"2025","journal-title":"Eur J Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.01.013","article-title":"Chronic stress increases metastasis via neutrophil-mediated changes to the microenvironment","volume":"42","author":"He","year":"2024","journal-title":"Cancer Cell"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.162.11.6473","article-title":"Glucocorticoids affect human dendritic cell differentiation and maturation","volume":"162","author":"Piemonti","year":"1999","journal-title":"J Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v95.10.3162","article-title":"Glucocorticoids transform CD40-triggering of dendritic cells into an alternative activation pathway resulting in antigen-presenting cells that secrete IL-10","volume":"95","author":"Rea","year":"2000","journal-title":"Blood"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2518983123","article-title":"Neutralization of acyl-CoA-binding protein attenuates glucocorticoid-mediated suppression of cancer immunosurveillance","volume":"123","author":"Pan","year":"2026","journal-title":"Proc Natl Acad Sci USA"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2016.08.014","article-title":"Tumor-derived immuno-modulators induce overlapping pro-tolerogenic gene expression signatures in human dendritic cells","volume":"77","author":"Trojandt","year":"2016","journal-title":"Hum Immunol"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1172\/jci164599","article-title":"Tumors produce glucocorticoids by metabolite recycling, not synthesis, and activate Tregs to promote growth","volume":"133","author":"Taves","year":"2023","journal-title":"J Clin Invest"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqag019","article-title":"Ovarian cancer cell glucocorticoid receptor activation increases myeloid-derived suppressor cell tumor infiltration","volume":"167","author":"Taya","year":"2026","journal-title":"Endocrinology"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2026.106978","article-title":"Steroid-induced modulation of the tumor immune microenvironment: Implications for cancer progression and immunotherapy outcomes","volume":"259","author":"Kaliyamoorthi","year":"2026","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2025.177376","article-title":"CK2: The master regulator in tumor immune-microenvironment - A crucial target in oncotherapy","volume":"994","author":"Karmakar","year":"2025","journal-title":"Eur J Pharmacol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbih.2022.100558","article-title":"Stress hormones are associated with inflammatory cytokines and attenuation of T-cell function in the ascites from patients with high grade serous ovarian cancer","volume":"26","author":"Aquino-Acevedo","year":"2022","journal-title":"Brain Behav Immun Health"},{"key":"B41","doi-asserted-by":"publisher","first-page":"843","DOI":"10.1186\/s40001-025-03073-6","article-title":"Nuclear receptors in metabolic, inflammatory, and oncologic diseases: mechanisms, therapeutic advances, and future directions","volume":"30","author":"Abdel-Rasol","year":"2025","journal-title":"Eur J Med Res"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-022-03151-2","article-title":"Divergent prognostic effects of pre-existing and treatment-emergent thyroid dysfunction in patients treated with immune checkpoint inhibitors","volume":"71","author":"von Itzstein","year":"2022","journal-title":"Cancer Immunol Immunother"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2024.2410557","article-title":"Exploring risk factors for endocrine-related immune-related adverse events: Insights from meta-analysis and Mendelian randomization","volume":"20","author":"Quan","year":"2024","journal-title":"Hum Vaccin Immunother"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2019.0250","article-title":"PD-L1 inhibitor-induced thyroiditis is associated with better overall survival in cancer patients","volume":"30","author":"Kotwal","year":"2020","journal-title":"Thyroid"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1743245","article-title":"Immune checkpoint inhibitors-induced thyroid dysfunction improves the prognosis of patients with lung cancer: a meta-analysis and systematic review","volume":"16","author":"Dong","year":"2025","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2019.0726","article-title":"Overt thyroid dysfunction and anti-thyroid antibodies predict response to anti-PD-1 immunotherapy in cancer patients","volume":"30","author":"Basak","year":"2020","journal-title":"Thyroid"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.18999\/nagjms.86.3.452","article-title":"Thyroid autoantibodies at baseline predict longer survival in non-small cell lung cancer patients treated with anti-programmed cell death-1 blockade: a prospective study","volume":"86","author":"Okuji","year":"2024","journal-title":"Nagoya J Med Sci"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/291546","article-title":"Obesity as a major risk factor for cancer","volume":"2013","author":"De Pergola","year":"2013","journal-title":"J Obes"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.00794","article-title":"Androgen-induced immunosuppression","volume":"9","author":"Gubbels Bupp","year":"2018","journal-title":"Front Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/s41574-025-01102-2","article-title":"Steroid hormones as modulators of anti-tumoural immunity","volume":"21","author":"Schwarzlmueller","year":"2025","journal-title":"Nat Rev Endocrinol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1654034","article-title":"Steroid hormone regulation of immunometabolism and inflammation","volume":"16","author":"Smith","year":"2025","journal-title":"Front Immunol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2025.217865","article-title":"The role of tumor microenvironment and immune cell crosstalk in triple-negative breast cancer (TNBC): Emerging therapeutic opportunities","volume":"628","author":"Sabit","year":"2025","journal-title":"Cancer Lett"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.1112234","article-title":"Postpartum hepatitis and host immunity in pregnant women with chronic HBV infection","volume":"13","author":"Zhang","year":"2022","journal-title":"Front Immunol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.102.1.42","article-title":"Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis Study (IRAS)","volume":"102","author":"Festa","year":"2000","journal-title":"Circulation"},{"key":"B55","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1038\/29795","article-title":"Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression","volume":"394","author":"Lord","year":"1998","journal-title":"Nature"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.08.145","article-title":"Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes","volume":"323","author":"Wolf","year":"2004","journal-title":"Biochem Biophys Res Commun"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/j.esmoop.2021.100095","article-title":"Body composition as a modulator of response to immunotherapy in lung cancer: time to deal with it","volume":"6","author":"Trestini","year":"2021","journal-title":"ESMO Open"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(18)30078-0","article-title":"Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: a retrospective, multicohort analysis","volume":"19","author":"McQuade","year":"2018","journal-title":"Lancet Oncol"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.5241","article-title":"Association between body mass index and overall survival with immune checkpoint inhibitor therapy for advanced non-small cell lung cancer","volume":"6","author":"Kichenadasse","year":"2020","journal-title":"JAMA Oncol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2017.99","article-title":"The 'obesity paradox' may not be a paradox at all","volume":"41","author":"Banack","year":"2017","journal-title":"Int J Obes (Lond)"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/s2213-8587(24)00316-4","article-title":"Definition and diagnostic criteria of clinical obesity","volume":"13","author":"Rubino","year":"2025","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2009.01.015","article-title":"Prognostic significance of bioelectrical impedance phase angle in advanced cancer: preliminary observations","volume":"25","author":"Santarpia","year":"2009","journal-title":"Nutrition"},{"key":"B63","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1016\/j.bpa.2011.07.006","article-title":"Hypoalbuminaemia in the perioperative period: clinical significance and management options","volume":"25","author":"Neel","year":"2011","journal-title":"Best Pract Res Clin Anaesthesiol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20720","article-title":"Albumin: biochemical properties and therapeutic potential","volume":"41","author":"Quinlan","year":"2005","journal-title":"Hepatology"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17010037","article-title":"Prognostic value of blood-based inflammatory markers in cancer patients receiving immune checkpoint inhibitors","volume":"17","author":"Midik","year":"2024","journal-title":"Cancers (Basel)"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2022-005670","article-title":"Serum albumin: a pharmacokinetic marker for optimizing treatment outcome of immune checkpoint blockade","volume":"10","author":"Zheng","year":"2022","journal-title":"J Immunother Cancer"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.4251\/wjgo.v14.i6.1124","article-title":"Glutamine deprivation impairs function of infiltrating CD8(+) T cells in hepatocellular carcinoma by inducing mitochondrial damage and apoptosis","volume":"14","author":"Wang","year":"2022","journal-title":"World J Gastrointest Oncol"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3390\/cancers16091709","article-title":"Immune system disorder and cancer-associated cachexia","volume":"16","author":"Zhang","year":"2024","journal-title":"Cancers (Basel)"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1623150","article-title":"Risk factors for steroid-refractory in immune checkpoint inhibitor-induced colitis: a retrospective cohort study","volume":"16","author":"Meng","year":"2025","journal-title":"Front Immunol"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2011.03.028","article-title":"A comparison of inflammation-based prognostic scores in patients with cancer. A Glasgow Inflammation Outcome Study","volume":"47","author":"Proctor","year":"2011","journal-title":"Eur J Cancer"},{"key":"B71","doi-asserted-by":"publisher","first-page":"435","DOI":"10.3892\/ol.2025.15181","article-title":"Usefulness of the preoperative Prognostic Immune and Nutritional Index as a prognostic predictor for patients with gastric cancer","volume":"30","author":"Li","year":"2025","journal-title":"Oncol Lett"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2010.04315.x","article-title":"Regulation of cytokine responses by seasonality of vitamin D status in healthy individuals","volume":"164","author":"Khoo","year":"2011","journal-title":"Clin Exp Immunol"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1102412","article-title":"Vitamin D inhibits monocyte\/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1","volume":"188","author":"Zhang","year":"2012","journal-title":"J Immunol"},{"key":"B74","doi-asserted-by":"publisher","first-page":"4853","DOI":"10.1038\/s41598-018-23258-w","article-title":"Vitamin D alleviates lead induced renal and testicular injuries by immunomodulatory and antioxidant mechanisms in rats","volume":"8","author":"BaSalamah","year":"2018","journal-title":"Sci Rep"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.7150\/thno.84645","article-title":"1alpha,25(OH)(2)D(3) ameliorates insulin resistance by alleviating gammadelta T cell inflammation via enhancing fructose-1,6-bisphosphatase 1 expression","volume":"13","author":"Li","year":"2023","journal-title":"Theranostics"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.3390\/cimb46120807","article-title":"The anti-inflammatory roles of vitamin D for improving human health","volume":"46","author":"Fenercioglu","year":"2024","journal-title":"Curr Issues Mol Biol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1851","article-title":"Vitamin D controls T cell antigen receptor signaling and activation of human T cells","volume":"11","author":"von Essen","year":"2010","journal-title":"Nat Immunol"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1136\/jitc-2021-003477","article-title":"1alpha,25(OH)(2)D(3) reverses exhaustion and enhances antitumor immunity of human cytotoxic T cells","volume":"10","author":"Li","year":"2022","journal-title":"J Immunother Cancer"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1126\/science.adh7954","article-title":"Vitamin D regulates microbiome-dependent cancer immunity","volume":"384","author":"Giampazolias","year":"2024","journal-title":"Science"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.34718","article-title":"Vitamin D supplementation increases objective response rate and prolongs progression-free time in patients with advanced melanoma undergoing anti-PD-1 therapy","volume":"129","author":"Galus","year":"2023","journal-title":"Cancer"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2025.10.037","article-title":"Vitamin D deficiency is associated with lower overall survival in patients receiving immune checkpoint inhibitors for cancer: A population-based cohort study using the TriNetX database","volume":"94","author":"Braun","year":"2026","journal-title":"J Am Acad Dermatol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.839816","article-title":"Low vitamin D status predicts poor clinical outcome in advanced melanoma treated with immune checkpoint or BRAF\/MEK inhibitors: A prospective non-interventional side-by-side analysis","volume":"12","author":"Reichrath","year":"2022","journal-title":"Front Oncol"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2318420121","article-title":"Iron regulates the quiescence of naive CD4 T cells by controlling mitochondria and cellular metabolism","volume":"121","author":"Kumar","year":"2024","journal-title":"Proc Natl Acad Sci USA"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpharm.2025.126091","article-title":"Self-amplifying ROS-responsive trinity nanodelivery system for enhanced cancer therapy","volume":"683","author":"Deng","year":"2025","journal-title":"Int J Pharm"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.3390\/cells10020303","article-title":"Iron metabolism in the tumor microenvironment-implications for anti-cancer immune response","volume":"10","author":"Sacco","year":"2021","journal-title":"Cells"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1255443","article-title":"The crosstalk of CD8+ T cells and ferroptosis in cancer","volume":"14","author":"Lin","year":"2023","journal-title":"Front Immunol"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1726210","article-title":"Iron-fueled ferroptosis: a new axis for immunomodulation to overcome cancer drug resistance-from immune microenvironment crosstalk to therapeutic translation","volume":"16","author":"Wu","year":"2025","journal-title":"Front Immunol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1170-y","article-title":"CD8(+) T cells regulate tumour ferroptosis during cancer immunotherapy","volume":"569","author":"Wang","year":"2019","journal-title":"Nature"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1038\/s41589-019-0462-8","article-title":"Redox lipid reprogramming commands susceptibility of macrophages and microglia to ferroptotic death","volume":"16","author":"Kapralov","year":"2020","journal-title":"Nat Chem Biol"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109235","article-title":"The glutathione peroxidase Gpx4 prevents lipid peroxidation and ferroptosis to sustain Treg cell activation and suppression of antitumor immunity","volume":"35","author":"Xu","year":"2021","journal-title":"Cell Rep"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-25-0101","article-title":"PF-08046032: A novel, investigational CD25-directed antibody-drug conjugate optimized for selective depletion of regulatory T cells in advanced Malignant tumors","volume":"24","author":"Abdelhamed","year":"2025","journal-title":"Mol Cancer Ther"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202303568","article-title":"A triple-responsive polymeric prodrug nanoplatform with extracellular ROS consumption and intracellular H(2)O(2) self-generation for imaging-guided tumor chemo-ferroptosis-immunotherapy","volume":"13","author":"Li","year":"2024","journal-title":"Adv Healthc Mater"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1017\/S0954422424000234","article-title":"The influence of zinc levels on osteoarthritis: A comprehensive review","volume":"38","author":"Tekeoglu","year":"2025","journal-title":"Nutr Res Rev"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18102222","article-title":"Zinc signals and immunity","volume":"18","author":"Maywald","year":"2017","journal-title":"Int J Mol Sci"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2007.10.013","article-title":"Clinical, immunological, anti-inflammatory and antioxidant roles of zinc","volume":"43","author":"Prasad","year":"2008","journal-title":"Exp Gerontol"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.1997.272.6.e1002","article-title":"Changes in cytokine production and T cell subpopulations in experimentally induced zinc-deficient humans","volume":"272","author":"Beck","year":"1997","journal-title":"Am J Physiol"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1017\/s0007114507832971","article-title":"Selected vitamins and trace elements support immune function by strengthening epithelial barriers and cellular and humoral immune responses","volume":"98","author":"Maggini","year":"2007","journal-title":"Br J Nutr"},{"key":"B98","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s10787-017-0309-4","article-title":"Antioxidant and anti-inflammatory effects of zinc. Zinc-dependent NF-kappaB signaling","volume":"25","author":"Jarosz","year":"2017","journal-title":"Inflammopharmacology"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2011.11.002","article-title":"The immunological contribution of NF-kappaB within the tumor microenvironment: a potential protective role of zinc as an anti-tumor agent","volume":"1825","author":"Bao","year":"2012","journal-title":"Biochim Biophys Acta"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1689317","article-title":"Nutritional intervention alleviates T cell exhaustion and empowers anti-tumor immunity","volume":"16","author":"Xu","year":"2025","journal-title":"Front Immunol"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.11.003","article-title":"Mannose metabolism reshapes T cell differentiation to enhance anti-tumor immunity","volume":"43","author":"Qiu","year":"2025","journal-title":"Cancer Cell"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2024.03.011","article-title":"Cancer SLC6A6-mediated taurine uptake transactivates immune checkpoint genes and induces exhaustion in CD8(+) T cells","volume":"187","author":"Cao","year":"2024","journal-title":"Cell"},{"key":"B103","doi-asserted-by":"publisher","first-page":"106661","DOI":"10.1016\/j.biocel.2024.106661","article-title":"Unveiling the role of taurine and SLC6A6 in tumor immune evasion: Implications for gastric cancer therapy","volume":"176","author":"Shentu","year":"2024","journal-title":"Int J Biochem Cell Biol"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2024.02.004","article-title":"Retinoic acid receptor activation reprograms senescence response and enhances anti-tumor activity of natural killer cells","volume":"42","author":"Colucci","year":"2024","journal-title":"Cancer Cell"},{"key":"B105","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1186\/s12964-025-02161-8","article-title":"Retinoic acid enhances gammadelta T cell cytotoxicity in nasopharyngeal carcinoma by reversing immune exhaustion","volume":"23","author":"Liu","year":"2025","journal-title":"Cell Commun Signal"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.3390\/nu13030886","article-title":"The interplay between the gut microbiome and the immune system in the context of infectious diseases throughout life and the role of nutrition in optimizing treatment strategies","volume":"13","author":"Wiertsema","year":"2021","journal-title":"Nutrients"},{"key":"B107","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/s41538-025-00698-z","article-title":"Composite dietary fiber alleviates obesity-induced skeletal muscle atrophy by regulating gut microbiota-derived short-chain fatty acids in mice","volume":"10","author":"Xie","year":"2026","journal-title":"NPJ Sci Food"},{"key":"B108","doi-asserted-by":"publisher","first-page":"4457","DOI":"10.1038\/s41467-020-18262-6","article-title":"Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity","volume":"11","author":"Yang","year":"2020","journal-title":"Nat Commun"},{"key":"B109","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0179586","article-title":"Butyrate modifies intestinal barrier function in IPEC-J2 cells through a selective upregulation of tight junction proteins and activation of the Akt signaling pathway","volume":"12","author":"Yan","year":"2017","journal-title":"PloS One"},{"key":"B110","doi-asserted-by":"publisher","first-page":"988","DOI":"10.1016\/j.cmet.2021.03.002","article-title":"Gut microbial metabolites facilitate anticancer therapy efficacy by modulating cytotoxic CD8(+) T cell immunity","volume":"33","author":"He","year":"2021","journal-title":"Cell Metab"},{"key":"B111","doi-asserted-by":"publisher","first-page":"2249143","DOI":"10.1080\/19490976.2023.2249143","article-title":"Microbial metabolite butyrate promotes anti-PD-1 antitumor efficacy by modulating T cell receptor signaling of cytotoxic CD8 T cell","volume":"15","author":"Zhu","year":"2023","journal-title":"Gut Microbes"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10391","article-title":"Intestinal microbiome analyses identify melanoma patients at risk for checkpoint-blockade-induced colitis","volume":"7","author":"Dubin","year":"2016","journal-title":"Nat Commun"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01698-2","article-title":"Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1","volume":"28","author":"McCulloch","year":"2022","journal-title":"Nat Med"},{"key":"B114","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1038\/s41571-025-01026-w","article-title":"Roles of the gut microbiota in immune-related adverse events: mechanisms and therapeutic intervention","volume":"22","author":"Gao","year":"2025","journal-title":"Nat Rev Clin Oncol"},{"key":"B115","doi-asserted-by":"publisher","first-page":"101478","DOI":"10.1016\/j.xcrm.2024.101478","article-title":"Modulating gut microbiome in cancer immunotherapy: Harnessing microbes to enhance treatment efficacy","volume":"5","author":"Kang","year":"2024","journal-title":"Cell Rep Med"},{"key":"B116","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1126\/science.abf3363","article-title":"Fecal microbiota transplant overcomes resistance to anti-PD-1 therapy in melanoma patients","volume":"371","author":"Davar","year":"2021","journal-title":"Science"},{"key":"B117","doi-asserted-by":"publisher","first-page":"118948","DOI":"10.1016\/j.biopha.2025.118948","article-title":"Protecting the endocrine axis in immuno-oncology: GLP-1 receptor agonists as host-directed modulators in colorectal cancer","volume":"194","author":"Saghafi","year":"2026","journal-title":"BioMed Pharmacother"},{"key":"B118","doi-asserted-by":"publisher","first-page":"9029","DOI":"10.1038\/s41598-021-88307-3","article-title":"Association of blood biomarkers and autoimmunity with immune related adverse events in patients with cancer treated with immune checkpoint inhibitors","volume":"11","author":"Michailidou","year":"2021","journal-title":"Sci Rep"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1002\/jrsm.1201","article-title":"Meta-analysis of prognostic studies for a biomarker with a study-specific cutoff value","volume":"7","author":"Sadashima","year":"2016","journal-title":"Res Synth Methods"},{"key":"B120","doi-asserted-by":"publisher","first-page":"103821","DOI":"10.1016\/j.breast.2024.103821","article-title":"Chemotherapy in older patients with early breast cancer","volume":"78","author":"Schmidt","year":"2024","journal-title":"Breast"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1097\/CJI.0000000000000469","article-title":"Vitamin D status is associated with immune checkpoint inhibitor efficacy and immune-related adverse event severity in lung cancer patients: A prospective cohort study","volume":"46","author":"You","year":"2023","journal-title":"J Immunother"},{"key":"B122","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1186\/s12885-022-10296-x","article-title":"Multicentre, randomised, open-label, parallel-group, clinical phase II study to evaluate immunonutrition in improving efficacy of immunotherapy in patients with metastatic non-small cell lung cancer, undergoing systematic nutritional counseling","volume":"22","author":"Caccialanza","year":"2022","journal-title":"BMC Cancer"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2025.1706534","article-title":"Prognostic value of Prognostic Nutritional Index in cancer: an umbrella review of systematic review and meta-analysis","volume":"12","author":"Yang","year":"2026","journal-title":"Front Nutr"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.3390\/medicina61101763","article-title":"The prognostic immune and nutritional index as a predictor of survival in resected non-small cell lung cancer","volume":"61","author":"An","year":"2025","journal-title":"Med (Kaunas)"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S499094","article-title":"The effect of systemic immune-inflammatory index (SII) and prognostic nutritional index (PNI) in early gastric cancer","volume":"17","author":"Jing","year":"2024","journal-title":"J Inflammation Res"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12162","article-title":"The mTOR pathway and integrating immune regulation","volume":"140","author":"Cobbold","year":"2013","journal-title":"Immunology"},{"key":"B127","doi-asserted-by":"publisher","first-page":"3296","DOI":"10.1038\/s41467-018-05854-6","article-title":"The tumor suppressor menin prevents effector CD8 T-cell dysfunction by targeting mTORC1-dependent metabolic activation","volume":"9","author":"Suzuki","year":"2018","journal-title":"Nat Commun"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2556","article-title":"Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation","volume":"14","author":"Sinclair","year":"2013","journal-title":"Nat Immunol"},{"key":"B129","doi-asserted-by":"publisher","first-page":"OF1","DOI":"10.1158\/2159-8290.CD-NW2026-0002","article-title":"GLP-1s spur greater reduction in colorectal cancer risk than aspirin","volume":"16","year":"2026","journal-title":"Cancer Discov"},{"key":"B130","doi-asserted-by":"publisher","first-page":"156113","DOI":"10.1016\/j.metabol.2024.156113","article-title":"Effect of glucagon-like peptide-1 receptor agonists and co-agonists on body composition: Systematic review and network meta-analysis","volume":"164","author":"Karakasis","year":"2025","journal-title":"Metabolism"},{"key":"B131","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1056\/NEJMoa2032183","article-title":"Once-weekly semaglutide in adults with overweight or obesity","volume":"384","author":"Wilding","year":"2021","journal-title":"N Engl J Med"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1111\/dom.16275","article-title":"Body composition changes during weight reduction with tirzepatide in the SURMOUNT-1 study of adults with obesity or overweight","volume":"27","author":"Look","year":"2025","journal-title":"Diabetes Obes Metab"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2206038","article-title":"Tirzepatide once weekly for the treatment of obesity","volume":"387","author":"Jastreboff","year":"2022","journal-title":"N Engl J Med"},{"key":"B134","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s13668-025-00649-w","article-title":"Impact of GLP-1 receptor agonist therapy in patients high risk for sarcopenia","volume":"14","author":"Memel","year":"2025","journal-title":"Curr Nutr Rep"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a029793","article-title":"Skeletal muscle as an endocrine organ: the role of myokines in exercise adaptations","volume":"7","author":"Hoffmann","year":"2017","journal-title":"Cold Spring Harb Perspect Med"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1084\/jem.191.5.771","article-title":"Reversible defects in natural killer and memory CD8 T cell lineages in interleukin 15-deficient mice","volume":"191","author":"Kennedy","year":"2000","journal-title":"J Exp Med"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.10.034","article-title":"Skeletal muscle as potential central link between sarcopenia and immune senescence","volume":"49","author":"Nelke","year":"2019","journal-title":"EBioMedicine"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-021-02888-6","article-title":"Sarcopenia and the risk of adverse events in patients treated with immune checkpoint inhibitors: a systematic review","volume":"70","author":"Guzman-Prado","year":"2021","journal-title":"Cancer Immunol Immunother"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1373\/jalm.2017.025809","article-title":"Study design considerations for cancer biomarker discoveries","volume":"3","author":"Zheng","year":"2018","journal-title":"J Appl Lab Med"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1080\/00365513.2016.1210334","article-title":"Standardization of tumor markers - priorities identified through external quality assessment","volume":"245","author":"Sturgeon","year":"2016","journal-title":"Scand J Clin Lab Invest Suppl"},{"key":"B141","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2020-1859","article-title":"How to meet ISO15189:2012 pre-analytical requirements in clinical laboratories? A consensus document by the EFLM WG-PRE","volume":"59","author":"Vermeersch","year":"2021","journal-title":"Clin Chem Lab Med"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.1111\/cts.70377","article-title":"Use of biomarkers in drug development for regulatory purposes","volume":"18","author":"Schuck","year":"2025","journal-title":"Clin Transl Sci"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1021\/acsnano.4c07213","article-title":"Carrier-free photodynamic bioregulators inhibiting lactic acid efflux combined with immune checkpoint blockade for triple-negative breast cancer immunotherapy","volume":"18","author":"Chen","year":"2024","journal-title":"ACS Nano"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1857147\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T04:24:37Z","timestamp":1786595077000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1857147\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,13]]},"references-count":143,"alternative-id":["10.3389\/fimmu.2026.1857147"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1857147","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,13]]},"article-number":"1857147"}}