{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:41:40Z","timestamp":1787067700797,"version":"build-2736575974"},"reference-count":65,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T00:00:00Z","timestamp":1644537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001343","name":"University of Pretoria","doi-asserted-by":"publisher","award":["Not applicable"],"award-info":[{"award-number":["Not applicable"]}],"id":[{"id":"10.13039\/501100001343","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>\n                    Xeroderma Pigmentosum (XP), an autosomal recessive disorder characterized by ultraviolet radiation-induced abnormalities of DNA excision and repair pathways is associated with early development of cutaneous cancers. Intracellular oxidative stress has also been proposed as a contributor to the occurrence of skin cancers. However, little is known about the possible augmentative contributions of chronic inflammation, immune suppression and oxidative stress to the pathogenesis of malignancies associated with other subtypes of XP. This has been addressed in the current study, focused on the measurement of systemic biomarkers of inflammation, immune dysfunction and oxidative damage in XP patients, consisting of XP-C, XP-D and XP-E cases, including those XP-C cases who had already developed multiple skin malignancies. The inflammatory biomarker profile measured in XP patients and healthy control subjects included the cytokines, interleukins (ILs)-2, -4, -6, -10, interferon-\u03b3 (IFN- \u03b3) and tumor-necrosis factor-\u03b1 (TNF-\u03b1), the acute phase reactant, C-reactive protein (CRP), and cotinine (as an objective indicator of smoking status). Immune suppression was detected according to the levels of five soluble inhibitory immune checkpoint proteins (CTLA-4, PD-1, PD-L1, LAG-3 and TIM-3), as well as those of vitamin D, while oxidative stress was determined according to the circulating levels of the DNA adduct, 8-hydroxy-2-deoxyguanosine (8-OH-dG). These various biomarkers were measured in plasma using immunofluorimetric, nephelometric and ELISA procedures. Significant elevations in IL-6 (\n                    <jats:italic>P<\/jats:italic>\n                    &amp;lt;0.01) and TNF-\u03b1 (\n                    <jats:italic>P<\/jats:italic>\n                    &amp;lt;0.0001), but none of the other cytokines, as well as increased levels of all five soluble inhibitory immune checkpoints (\n                    <jats:italic>P<\/jats:italic>\n                    =0.032-\n                    <jats:italic>P<\/jats:italic>\n                    =0.0001) were detected in the plasma of the XP patients. C-reactive protein and vitamin D were increased and decreased, respectively (both\n                    <jats:italic>P<\/jats:italic>\n                    &amp;lt;0.0001), while only one participant had an elevated level of plasma cotinine. Surprisingly, the levels of 8-OH-dG were significantly (\n                    <jats:italic>P<\/jats:italic>\n                    =0.0001) lower in the group of XP patients relative to a group of healthy control subjects. The findings of increased levels of pro-inflammatory cytokines and, in particular, those of the soluble immune checkpoints, in the setting of decreased vitamin D and moderately elevated levels of CRP in XP patients suggest a possible secondary role of ongoing, inflammatory stress and immune suppression in the pathogenesis of XP-associated malignancies.\n                  <\/jats:p>","DOI":"10.3389\/fonc.2022.819790","type":"journal-article","created":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T04:43:01Z","timestamp":1644554581000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Elevated Levels of Soluble CTLA-4, PD-1, PD-L1, LAG-3 and TIM-3 and Systemic Inflammatory Stress as Potential Contributors to Immune Suppression and Generalized Tumorigenesis in a Cohort of South African Xeroderma Pigmentosum Patients"],"prefix":"10.3389","volume":"12","author":[{"given":"Mahlatse C. M.","family":"Kgokolo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shalate C.","family":"Siwele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen C.","family":"Steel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luyanda L. I.","family":"Kwofie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mike M.","family":"Sathekge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter W. A.","family":"Meyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernardo L.","family":"Rapoport","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald","family":"Anderson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,2,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.123.2.241","article-title":"Xeroderma Pigmentosum. Cutaneous, Ocular, and Neurologic Abnormalities in 830 Published Cases","volume":"123","author":"Kraemer","year":"1987","journal-title":"Arch Dermatol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2010.083022","article-title":"Cancer and Neurologic Degeneration in Xeroderma Pigmentosum: Long Term Follow-Up Characterises the Role of DNA Repair","volume":"48","author":"Bradford","year":"2011","journal-title":"J Med Genet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2011.00098","article-title":"Chronic Inflammation in Cancer Development","volume":"2","author":"Multhoff","year":"2012","journal-title":"Front Immunol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of Cancer: The Next Generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22105123","article-title":"PD-1\/PD-L1 in Cancer: Pathophysiological, Diagnostic and Therapeutic Aspects","volume":"22","author":"Munari","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00074.2003","article-title":"IL-6 Enhances Plasma IL-1ra, IL-10, and Cortisol in Humans","volume":"285","author":"Steensberg","year":"2003","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1136\/jech.2006.051292","article-title":"A Systematic Review of the Association Between Circulating Concentrations of C Reactive Protein and Cancer","volume":"61","author":"Heikkil\u00e4","year":"2007","journal-title":"J Epidemiol Community Health"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1001\/jama.291.5.585","article-title":"Helzlsouer KJ. C-Reactive Protein and the Risk of Incident Colorectal Cancer","volume":"291","author":"Erlinger","year":"2004","journal-title":"JAMA"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-05-0316","article-title":"Circulating Levels of Inflammatory Markers and Cancer Risk in the Health Aging and Body Composition Cohort","volume":"14","author":"Il\u2019yasova","year":"2005","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-3631","article-title":"A Prospective Study of Serum C-Reactive Protein and Colorectal Cancer Risk in Men","volume":"66","author":"Gunter","year":"2006","journal-title":"Cancer Res"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.19.8440","article-title":"Baseline C-Reactive Protein Is Associated With Incident Cancer and Survival in Patients With Cancer","volume":"27","author":"Allin","year":"2009","journal-title":"J Clin Oncol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.27.0454","article-title":"C-Reactive Protein and Risk of Lung Cancer","volume":"28","author":"Chaturvedi","year":"2010","journal-title":"J Clin Oncol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2010.07.032","article-title":"C-Reactive Protein-Associated Genetic Variants and Cancer Risk: Findings From FINRISK 1992, FINRISK 1997 and Health 2000 Studies","volume":"47","author":"Heikkil\u00e4","year":"2011","journal-title":"Eur J Cancer"},{"key":"B14","doi-asserted-by":"publisher","first-page":"e7822","DOI":"10.1097\/MD.0000000000007822","article-title":"Guo R. C-Reactive Protein and Risk of Ovarian Cancer: A Systematic Review and Meta-Analysis","volume":"96","author":"Li","year":"2017","journal-title":"Med (Baltimore)"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23461","article-title":"Et Al; ASCENT Investigators. C-Reactive Protein as a Prognostic Marker for Men With Androgen-Independent Prostate Cancer: Results From the ASCENT Trial","volume":"112","author":"Beer","year":"2008","journal-title":"Cancer"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0202555","article-title":"Serum C-Reactive Protein Is an Important and Powerful Prognostic Biomarker in Most Adult Solid Tumors","volume":"13","author":"Shrotriya","year":"2018","journal-title":"PloS One"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1530\/EC-19-0132","article-title":"C-Reactive Protein (CRP) Promotes Malignant Properties in Pancreatic Neuroendocrine Neoplasms","volume":"8","author":"Schimmack","year":"2019","journal-title":"Endocr Connect"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.2217\/fon-2019-0063","article-title":"Preoperative High C-Reactive Protein\/Albumin Ratio Is a Poor Prognostic Factor of Oral Squamous Cell Carcinoma","volume":"15","author":"Wang","year":"2019","journal-title":"Future Oncol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000016238","article-title":"Long G. C-Reactive Protein Is a Significant Predictor of Improved Survival in Patients With Advanced Non-Small Cell Lung Cancer","volume":"98","author":"Xiao","year":"2019","journal-title":"Med (Baltimore)"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e0193693","DOI":"10.1371\/journal.pone.0193693","article-title":"The Prevalence of Deranged C-Reactive Protein and Albumin in Patients With Incurable Cancer Approaching Death","volume":"13","author":"Gray","year":"2018","journal-title":"PloS One"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2019.37.15_suppl.100","article-title":"Serum IL-6 and CRP as Prognostic Factors in Melanoma Patients Receiving Single Agent and Combination Checkpoint Inhibition. Abstract Presented at the 2019 ASCO Annual Meeting","volume":"37","author":"Weber","year":"2019","journal-title":"J Clin Oncol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/149185","article-title":"Chronic Inflammation and Cytokines in the Tumor Microenvironment","volume":"2014","author":"Landskron","year":"2014","journal-title":"J Immunol Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-020-0343-4","article-title":"Immune Checkpoint Signaling and Cancer Immunotherapy","volume":"30","author":"He","year":"2020","journal-title":"Cell Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-042020-042741","article-title":"Immune Checkpoint Inhibitors for the Treatment of Cancer: Clinical Impact and Mechanisms of Response and Resistance","volume":"16","author":"Bagchi","year":"2021","journal-title":"Annu Rev Pathol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/ejcn.2015.1","article-title":"High Prevalence of Vitamin D Deficiency in Patients With Xeroderma Pigmetosum-A Under Strict Sun Protection","volume":"69","author":"Kuwabara","year":"2015","journal-title":"Eur J Clin Nutr"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2020.25850","article-title":"Et Al; VITAL Research Group. Effect of Vitamin D3 Supplements on Development of Advanced Cancer: A Secondary Analysis of the VITAL Randomized Clinical Trial","volume":"3","author":"Chandler","year":"2020","journal-title":"JAMA Netw Open"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01307","article-title":"Vitamin D Controls Tumor Growth and CD8+ T Cell Infiltration in Breast Cancer","volume":"10","author":"Karkeni","year":"2019","journal-title":"Front Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-4362.1999.00724.x","article-title":"Xeroderma Pigmentosum in Black South Africans","volume":"38","author":"Jacyk","year":"1999","journal-title":"Int J Dermatol"},{"key":"B29","unstructured":"EichenfieldLF\n            WarnerCG\n          Xeroderma Pigmentosum"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.18030","article-title":"Xeroderma Pigmentosum in South Africa: Evidence for a Prevalent Founder Effect","volume":"181","author":"Kgokolo","year":"2019","journal-title":"Br J Dermatol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.7314\/apjcp.2015.16.10.4161","article-title":"Obesity and Obese-Related Chronic Low-Grade Inflammation in Promotion of Colorectal Cancer Development","volume":"16","author":"Pietrzyk","year":"2015","journal-title":"Asian Pac J Cancer Prev"},{"key":"B32","doi-asserted-by":"publisher","first-page":"10805","DOI":"10.1038\/s41598-018-29041-1","article-title":"Et Al; EnviroGenoMarkers. Association Between Low-Grade Inflammation and Breast Cancer and B-Cell Myeloma and Non-Hodgkin Lymphoma: Findings From Two Prospective Cohorts","volume":"8","author":"Berger","year":"2018","journal-title":"Sci Rep"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/27.15.3153","article-title":"Repair of Oxidative DNA Base Lesions Induced by Fluorescent Light Is Defective in Xeroderma Pigmentosum Group A Cells","volume":"27","author":"Lipinski","year":"1999","journal-title":"Nucleic Acids Res"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.10.2124","article-title":"Reconstitution of the Base Excision Repair Pathway for 7,8-Dihydro-8-Oxoguanine With Purified Human Proteins","volume":"30","author":"Pascucci","year":"2002","journal-title":"Nucleic Acids Res"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/mutage\/geq031","article-title":"DNA Repair and the Origins of Urinary Oxidized 2\u2019-Deoxyribonucleosides","volume":"25","author":"Evans","year":"2010","journal-title":"Mutagenesis"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.4994","article-title":"Oxidative Stress and the DNA Mismatch Repair Pathway","volume":"18","author":"Brierley","year":"2013","journal-title":"Antioxid Redox Signal"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.239.231","article-title":"Elevated Urinary Levels of 8-Hydroxy-2\u2019-Deoxyguanosine in a Japanese Child of Xeroderma Pigmentosum\/Cockayne Syndrome Complex With Infantile Onset of Nephrotic Syndrome","volume":"239","author":"Kondo","year":"2016","journal-title":"Tohoku J Exp Med"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/5741517","article-title":"Circadian Rhythms of Oxidative Stress Markers and Melatonin Metabolite in Patients With Xeroderma Pigmentosum Group A","volume":"2016","author":"Miyata","year":"2016","journal-title":"Oxid Med Cell Longev"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/978-0-387-09599-8_13","article-title":"Roles of Oxidative Stress in Xeroderma Pigmentosum","volume":"637","author":"Hayashi","year":"2008","journal-title":"Adv Exp Med Biol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1186\/s40425-018-0449-0","article-title":"Soluble Immune Checkpoints in Cancer: Production, Function and Biological Significance","volume":"6","author":"Gu","year":"2018","journal-title":"J Immunother Cancer"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01835","article-title":"The Dark Side of Fibroblasts: Cancer-Associated Fibroblasts as Mediators of Immunosuppression in the Tumor Microenvironment","volume":"10","author":"Monteran","year":"2019","journal-title":"Front Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13956","article-title":"Tumour Cell-Intrinsic CTLA4 Regulates PD-L1 Expression in Non-Small Cell Lung Cancer","volume":"23","author":"Zhang","year":"2019","journal-title":"J Cell Mol Med"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1111\/1759-7714.12247","article-title":"Circulating PD-L1 in NSCLC Patients and the Correlation Between the Level of PD-L1 Expression and the Clinical Characteristics","volume":"6","author":"Zhang","year":"2015","journal-title":"Thorac Cancer"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2016.03.002","article-title":"High Levels of the Soluble Programmed Death-Ligand (sPD-L1) Identify Hepatocellular Carcinoma Patients With a Poor Prognosis","volume":"59","author":"Finkelmeier","year":"2016","journal-title":"Eur J Cancer"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-016-2184-6","article-title":"Serum Levels of Soluble Programmed Cell Death Ligand 1 as a Prognostic Factor on the First-Line Treatment of Metastatic or Recurrent Gastric Cancer","volume":"142","author":"Takahashi","year":"2016","journal-title":"J Cancer Res Clin Oncol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.21873\/anticanres.13716","article-title":"Plasma Levels of Soluble PD-L1 Correlate With Tumor Regression in Patients With Lung and Gastric Cancer Treated With Immune Checkpoint Inhibitors","volume":"39","author":"Ando","year":"2019","journal-title":"Anticancer Res"},{"key":"B47","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1186\/s40425-019-0810-y","article-title":"Soluble Immune Checkpoint-Related Proteins as Predictors of Tumor Recurrence, Survival, and T Cell Phenotypes in Clear Cell Renal Cell Carcinoma Patients","volume":"7","author":"Wang","year":"2019","journal-title":"J Immunother Cancer"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.3390\/jpm11070651","article-title":"The Role of Soluble LAG3 and Soluble Immune Checkpoints Profile in Advanced Head and Neck Cancer: A Pilot Study","volume":"11","author":"Botticelli","year":"2021","journal-title":"J Pers Med"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)01206-X","article-title":"Immune Checkpoint Inhibitors in Melanoma","volume":"398","author":"Carlino","year":"2021","journal-title":"Lancet"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.137","article-title":"Et Al; Groupe Ouest-Est Des Leuc\u00e9mies Et Autres Maladies Du Sang; Groupe Ouest-Est Des Leuc\u00e9mies Et Autres Maladies Du Sang. High Level of Soluble Programmed Cell Death Ligand 1 in Blood Impacts Overall Survival in Aggressive Diffuse Large B-Cell Lymphoma: Results From a French Multicenter Clinical Trial","volume":"28","author":"Rossille","year":"2014","journal-title":"Leukemia"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.5682","article-title":"Serum Levels of Soluble Programmed Death Ligand 1 Predict Treatment Response and Progression Free Survival in Multiple Myeloma","volume":"6","author":"Wang","year":"2015","journal-title":"Oncotarget"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-017-1987-x","article-title":"Programmed Death-Ligand 1 and Its Soluble Form Are Highly Expressed in Nasal Natural Killer\/T-Cell Lymphoma: A Potential Rationale for Immunotherapy","volume":"66","author":"Nagato","year":"2017","journal-title":"Cancer Immunol Immunother"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1080\/16078454.2019.1590965","article-title":"Soluble Programmed Death-Ligand 1 Are Highly Expressed in Peripheral T-Cell Lymphoma: A Biomarker for Prognosis","volume":"24","author":"Shen","year":"2019","journal-title":"Hematology"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2019.9982","article-title":"Significance of PD-L1 in the Diagnosis and Treatment of B-Cell Malignant Lymphoma","volume":"17","author":"Yang","year":"2019","journal-title":"Oncol Lett"},{"key":"B55","article-title":"High Mutation Frequency in Ras Genes of Skin Tumors Isolated From DNA Repair Deficient Xeroderma Pigmentosum Patients","volume":"53","author":"Daya-Grosjean","year":"1993","journal-title":"Cancer Res"},{"key":"B56","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/978-0-387-09599-8_3","article-title":"Xeroderma Pigmentosum and Skin Cancer","volume":"637","author":"Daya-Grosjean","year":"2008","journal-title":"Adv Exp Med Biol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1046\/j.1365-2249.2000.01257.x","article-title":"Immunodeficiency Associated With DNA Repair Defects","volume":"121","author":"Gennery","year":"2000","journal-title":"Clin Exp Immunol"},{"key":"B58","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.ejca.2017.06.022","article-title":"Rapid Response of Metastatic Cutaneous Squamous Cell Carcinoma to Pembrolizumab in a Patient With Xeroderma Pigmentosum: Case Report and Review of the Literature","volume":"83","author":"Deinlein","year":"2017","journal-title":"Eur J Cancer"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.27966","article-title":"Immunotherapy in Xeroderma Pigmentosum: A Case of Advanced Cutaneous Squamous Cell Carcinoma Treated With Cemiplimab and a Literature Review","volume":"12","author":"Rubatto","year":"2021","journal-title":"Oncotarget"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13051148","article-title":"Cutaneous Squamous Cell Carcinoma in the Age of Immunotherapy","volume":"13","author":"Ishitsuka","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B61","unstructured":"MartinsRG\n          Systemic Treatment of Advanced Basal Cell and Cutaneous Squamous Cell Carcinomas Not Amenable to Local Therapies"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/j.ctrv.2018.05.016","article-title":"Italian Melanoma Intergroup (IMI). Vitamin D in Melanoma: Controversies and Potential Role in Combination With Immune Check-Point Inhibitors","volume":"69","author":"Stucci","year":"2018","journal-title":"Cancer Treat Rev"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02254","article-title":"Immunopathogenesis of Immune Checkpoint Inhibitor-Related Adverse Events: Roles of the Intestinal Microbiome and Th17 Cells","volume":"10","author":"Anderson","year":"2019","journal-title":"Front Immunol"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.32966","article-title":"Vitamin D Intake is Associated With Decreased Risk of Immune Checkpoint Inhibitor-Induced Colitis","volume":"126","author":"Grover","year":"2020","journal-title":"Cancer"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvaa046.598","article-title":"SAT-411 Vitamin D Levels and Risk of Thyroid Immune Related Adverse Events in Patients on Immune Checkpoint Inhibitors","volume":"4","author":"Newman","year":"2020","journal-title":"J Endocr Soc"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.819790\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,11]],"date-time":"2022-02-11T04:43:06Z","timestamp":1644554586000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.819790\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,11]]},"references-count":65,"alternative-id":["10.3389\/fonc.2022.819790"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2022.819790","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,11]]},"article-number":"819790"}}