{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T22:26:14Z","timestamp":1787955974838,"version":"build-2784847793"},"reference-count":100,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T00:00:00Z","timestamp":1655164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>We aimed to review the clinical and biological presentation of granulomatosis associated with immune-checkpoint inhibitors (ICI) in patients with melanoma and to explore its association with classical sarcoidosis as well as with cancer response to ICI. To this end, a retrospective study on 18 melanoma patients with histologically proven ICI-induced granulomatosis over a 12-year period in a single center, as well as on 67 similar cases reported in the literature, was conducted. Results indicate ICI-induced granulomatosis is an early side effect (median time to onset: 2 months). Its clinical presentation, with predominant (90%) thoracic involvement, histopathological appearance and supposed underlying biology (involving the mTOR pathway in immune cells, Th17 polarization and TReg dysfunction) are indistinguishable from those of sarcoidosis. Moreover, it appears to be associated with ICI benefit (&gt;65% objective response rate). Evolution is generally favorable, and symptomatic steroid treatment and\/or ICI discontinuation are rarely necessary. ICI-associated granulomatosis is critical to explore for several reasons. Practically, it is essential to differentiate it from cancer progression. Secondly, this \u201cexperimental\u201d sarcoidosis brings new elements that may help to address sarcoidosis origin and pathophysiology. Its association with ICI efficacy must be confirmed on a larger scale but could have significant impacts on patient management and biomarker definition.<\/jats:p>","DOI":"10.3390\/cancers14122937","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T23:50:14Z","timestamp":1655250614000},"page":"2937","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Sarcoid-like Granulomatosis Associated with Immune Checkpoint Inhibitors in Melanoma"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1419-8180","authenticated-orcid":false,"given":"Audrey","family":"Melin","sequence":"first","affiliation":[{"name":"Department of Dermatology, Gustave Roussy, 114 rue Edouard-Vaillant, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5881-5956","authenticated-orcid":false,"given":"\u00c9milie","family":"Routier","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Gustave Roussy, 114 rue Edouard-Vaillant, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9verine","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Gustave Roussy, 114 rue Edouard-Vaillant, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Pradere","sequence":"additional","affiliation":[{"name":"Service de Pneumologie et Transplantation Pulmonaire, H\u00f4pital Marie-Lannelongue, Groupe Hospitalier Paris-Saint Joseph, 133 Av. de la R\u00e9sistance, 92350 Le Plessis-Robinson, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerome","family":"Le Pavec","sequence":"additional","affiliation":[{"name":"Service de Pneumologie et Transplantation Pulmonaire, H\u00f4pital Marie-Lannelongue, Groupe Hospitalier Paris-Saint Joseph, 133 Av. de la R\u00e9sistance, 92350 Le Plessis-Robinson, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1783-9940","authenticated-orcid":false,"given":"Thibaut","family":"Pierre","sequence":"additional","affiliation":[{"name":"Department of Medical Imaging, Gustave Roussy, 114 rue Edouard-Vaillant, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"No\u00e9mie","family":"Chanson","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kremlin Bic\u00eatre Hospital, 78 rue du G\u00e9n\u00e9ral Leclerc, 94270 Le Kremlin Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1604-6823","authenticated-orcid":false,"given":"Jean-Yves","family":"Scoazec","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Saclay, AP-HP, 63 rue Gabriel P\u00e9ri, 94270 Le Kremlin Bic\u00eatre, France"},{"name":"Department of Pathology, Gustave Roussy, 114 rue Edouard-Vaillant, 94800 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Lambotte","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kremlin Bic\u00eatre Hospital, 78 rue du G\u00e9n\u00e9ral Leclerc, 94270 Le Kremlin Bic\u00eatre, France"},{"name":"Universit\u00e9 Paris Saclay, AP-HP, 63 rue Gabriel P\u00e9ri, 94270 Le Kremlin Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Robert","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Gustave Roussy, 114 rue Edouard-Vaillant, 94800 Villejuif, France"},{"name":"Universit\u00e9 Paris Saclay, AP-HP, 63 rue Gabriel P\u00e9ri, 94270 Le Kremlin Bic\u00eatre, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1200\/JCO.2014.56.2736","article-title":"Pooled Analysis of Long-Term Survival Data from Phase II and Phase III Trials of Ipilimumab in Unresectable or Metastatic Melanoma","volume":"33","author":"Schadendorf","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1056\/NEJMoa1412082","article-title":"Nivolumab in Previously Untreated Melanoma without BRAF Mutation","volume":"372","author":"Robert","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1056\/NEJMoa1910836","article-title":"Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma","volume":"381","author":"Larkin","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_4","unstructured":"National Cancer Institute (2006). Common Terminology Criteria for Adverse Events v3.0 (CTCAE)."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.clindermatol.2007.03.010","article-title":"Sarcoidosis and Malignancy","volume":"25","author":"Cohen","year":"2007","journal-title":"Clin. Dermatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1378\/chest.14-1475","article-title":"Sarcoidosis and Cancer Risk: Systematic Review and Meta-Analysis of Observational Studies","volume":"147","author":"Bonifazi","year":"2015","journal-title":"Chest"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1668","DOI":"10.1164\/ajrccm.160.5.9904045","article-title":"Increased Risk for Cancer Following Sarcoidosis","volume":"160","author":"Askling","year":"1999","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1159\/000213245","article-title":"Sarcoidosis and Melanoma: A Referral Center Study of 1,199 Cases","volume":"219","author":"Seve","year":"2009","journal-title":"Dermatology"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.3390\/cancers7020821","article-title":"Sarcoidosis in Melanoma Patients: Case Report and Literature Review","volume":"7","author":"Beutler","year":"2015","journal-title":"Cancers"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1046\/j.1365-2133.1997.19542042.x","article-title":"Malignant Melanoma and Granulomatosis","volume":"137","author":"Robert","year":"1997","journal-title":"Br. J. Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1046\/j.1365-2230.2003.01279.x","article-title":"Coexistence of Micrometastatic Melanoma Cells and Sarcoid Granulomas in All Regional Lymph Nodes in a Patient with Acral Melanoma","volume":"28","author":"Echigo","year":"2003","journal-title":"Clin. Exp. Dermatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1097\/00007611-198509000-00027","article-title":"Sarcoidosis: A Cause of Bilateral Hilar Lymphadenopathy after Excision of Malignant Melanoma of the Arm","volume":"78","author":"Rubinstein","year":"1985","journal-title":"South. Med. J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1002\/1097-0142(197802)41:2<562::AID-CNCR2820410224>3.0.CO;2-X","article-title":"Epithelioid Granulomas Associated with Hodgkin\u2019s Disease: Clinical Correlations in 55 Previously Untreated Patients","volume":"41","author":"Sacks","year":"1978","journal-title":"Cancer"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1097\/MCP.0000000000000800","article-title":"Drug-Induced Sarcoidosis-like Reactions","volume":"27","author":"Miedema","year":"2021","journal-title":"Curr. Opin. Pulm. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Cleven, K.L., Ye, K., Zeig-Owens, R., Hena, K.M., Montagna, C., Shan, J., Hosgood, H.D., Jaber, N., Weiden, M.D., and Colbeth, H.L. (2019). Genetic Variants Associated with FDNY WTC-Related Sarcoidosis. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16101830"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"503","DOI":"10.3389\/fgene.2018.00503","article-title":"Next-Generation Sequencing Based HLA Typing: Deciphering Immunogenetic Aspects of Sarcoidosis","volume":"9","author":"Kishore","year":"2018","journal-title":"Front. Genet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s12016-015-8477-8","article-title":"Immunogenetics of Disease-Causing Inflammation in Sarcoidosis","volume":"49","author":"Grunewald","year":"2015","journal-title":"Clin. Rev. Allergy Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1164\/rccm.201106-1143OC","article-title":"Sarcoidosis Blood Transcriptome Reflects Lung Inflammation and Overlaps with Tuberculosis","volume":"184","author":"Koth","year":"2011","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1183\/09031936.00002607","article-title":"Molecular Evidence for the Role of Mycobacteria in Sarcoidosis: A Meta-Analysis","volume":"30","author":"Gupta","year":"2007","journal-title":"Eur. Respir. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1084\/jem.20040429","article-title":"Mycobacterial Catalase-Peroxidase Is a Tissue Antigen and Target of the Adaptive Immune Response in Systemic Sarcoidosis","volume":"201","author":"Song","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_21","first-page":"25","article-title":"Prolonged Culture for Mycobacteria in Mediastinal Lymph Nodes from Patients with Pulmonary Sarcoidosis. A Negative Study","volume":"21","author":"Milman","year":"2004","journal-title":"Sarcoidosis Vasc. Diffus. Lung Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1128\/JCM.40.1.198-204.2002","article-title":"Quantitative Analysis of Mycobacterial and Propionibacterial DNA in Lymph Nodes of Japanese and European Patients with Sarcoidosis","volume":"40","author":"Eishi","year":"2002","journal-title":"J. Clin. Microbiol."},{"key":"ref_23","first-page":"256","article-title":"Proliferative Response of Peripheral Blood Mononuclear Cells and Levels of Antibody to Recombinant Protein from Propionibacterium Acnes DNA Expression Library in Japanese Patients with Sarcoidosis","volume":"17","author":"Ebe","year":"2000","journal-title":"Sarcoidosis Vasc. Diffus. Lung Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.3389\/fimmu.2019.01923","article-title":"IL-17A Can Promote Propionibacterium acnes-Induced Sarcoidosis-Like Granulomatosis in Mice","volume":"10","author":"Song","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_25","first-page":"33","article-title":"Propionibacterium Acnes Is the Most Common Bacterium Commensal in Peripheral Lung Tissue and Mediastinal Lymph Nodes from Subjects without Sarcoidosis","volume":"22","author":"Ishige","year":"2005","journal-title":"Sarcoidosis Vasc. Diffus. Lung Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0012-3692(15)37948-4","article-title":"Relationship of Environmental Exposures to the Clinical Phenotype of Sarcoidosis","volume":"128","author":"Kreider","year":"2005","journal-title":"Chest"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1164\/rccm.200402-249OC","article-title":"A Case Control Etiologic Study of Sarcoidosis: Environmental and Occupational Risk Factors","volume":"170","author":"Newman","year":"2004","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1159\/000161122","article-title":"Anti-CTLA4 Monoclonal Antibody Induced Sarcoidosis in a Metastatic Melanoma Patient","volume":"218","author":"Eckert","year":"2009","journal-title":"Dermatology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e156","DOI":"10.1200\/JCO.2011.39.3298","article-title":"Pulmonary Sarcoid-Like Granulomatosis Induced by Ipilimumab","volume":"30","author":"Berthod","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e7","DOI":"10.1200\/JCO.2011.37.9693","article-title":"Ipilimumab-Induced Sarcoidosis in a Patient with Metastatic Melanoma Undergoing Complete Remission","volume":"30","author":"Vogel","year":"2012","journal-title":"J. Clin. Oncol."},{"key":"ref_31","first-page":"1355","article-title":"Sarcoidosis in a Patient with Metastatic Melanoma Sequentially Treated with Anti-CTLA-4 Monoclonal Antibody and Selective BRAF Inhibitor","volume":"32","author":"Wilgenhof","year":"2012","journal-title":"Anticancer Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e272","DOI":"10.1016\/j.jaad.2013.07.028","article-title":"Cutaneous and Pulmonary Sarcoidosis-like Reaction Associated with Ipilimumab","volume":"69","author":"Reule","year":"2013","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e954506","DOI":"10.4161\/21624011.2014.954506","article-title":"Late Development of Splenic Sarcoidosis-like Lesions in a Patient with Metastatic Melanoma and Long-Lasting Clinical Response to Ipilimumab","volume":"3","author":"Andersen","year":"2014","journal-title":"Oncoimmunology"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1159\/000362614","article-title":"New-Onset Mediastinal and Central Nervous System Sarcoidosis in a Patient with Metastatic Melanoma Undergoing CTLA4 Monoclonal Antibody Treatment","volume":"37","author":"Murphy","year":"2014","journal-title":"Oncol. Res. Treat."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e133","DOI":"10.1016\/j.chest.2015.10.082","article-title":"Nivolumab-Induced Sarcoid-Like Granulomatous Reaction in a Patient with Advanced Melanoma","volume":"149","author":"Danlos","year":"2016","journal-title":"Chest"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1111\/dth.12380","article-title":"Cutaneous Sarcoidosis in a Melanoma Patient under Ipilimumab Therapy","volume":"29","year":"2016","journal-title":"Dermatol. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s40425-016-0117-1","article-title":"Systemic Inflammation in a Melanoma Patient Treated with Immune Checkpoint Inhibitors-an Autopsy Study","volume":"4","author":"Koelzer","year":"2016","journal-title":"J. Immunother. Cancer"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1186\/s40425-016-0199-9","article-title":"Sarcoidosis in the Setting of Combination Ipilimumab and Nivolumab Immunotherapy: A Case Report & Review of the Literature","volume":"4","author":"Reuss","year":"2016","journal-title":"J. Immunother. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1111\/bjd.14808","article-title":"Pulmonary Sarcoid-like Granulomatosis Induced by Nivolumab","volume":"176","author":"Pradelli","year":"2017","journal-title":"Br. J. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1097\/CJI.0000000000000181","article-title":"Sarcoidosis Following Anti-PD-1 and Anti-CTLA-4 Therapy for Metastatic Melanoma","volume":"40","author":"Reddy","year":"2017","journal-title":"J. Immunother."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1159\/000491599","article-title":"Neurosarcoidosis Following Immune Checkpoint Inhibition","volume":"11","author":"Shah","year":"2018","journal-title":"Case Rep. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1158\/2326-6066.CIR-17-0715","article-title":"Sarcoid-Like Granulomatosis of the Lung Related to Immune-Checkpoint Inhibitors: Distinct Clinical and Imaging Features of a Unique Immune-Related Adverse Event","volume":"6","author":"Nishino","year":"2018","journal-title":"Cancer Immunol. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1016\/j.rmr.2018.08.003","article-title":"Sarcoid-like granulomatosis in cancer patients treated with immune checkpoints inhibitors","volume":"35","author":"Faviez","year":"2018","journal-title":"Rev. Mal. Respir."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1177\/1203475418776934","article-title":"Erythema Nodosum as the Initial Presentation of Nivolumab-Induced Sarcoidosis-Like Reaction","volume":"22","author":"Laroche","year":"2018","journal-title":"J. Cutan. Med. Surg."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.revmed.2017.11.008","article-title":"Sarcoidosis Post-Anti-PD-1 Therapy, Mimicking Relapse of Metastatic Melanoma in a Patient Undergoing Complete Remission","volume":"39","author":"Yatim","year":"2018","journal-title":"Rev. Med. Interne"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"e327","DOI":"10.1016\/S1470-2045(18)30252-3","article-title":"Checkpoint Inhibitor-Induced Sarcoid Reaction Mimicking Bone Metastases","volume":"19","author":"Jespersen","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1097\/CMR.0000000000000437","article-title":"Sarcoid-like Reactions in Patients Receiving Modern Melanoma Treatment","volume":"28","author":"Dimitriou","year":"2018","journal-title":"Melanoma Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1097\/RLU.0000000000002408","article-title":"FDG PET\/CT Course of Pembrolizumab-Associated Multiorgan Sarcoidosis","volume":"44","author":"Lu","year":"2019","journal-title":"Clin. Nucl. Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s40425-018-0323-0","article-title":"Granulomatous\/Sarcoid-like Lesions Associated with Checkpoint Inhibitors: A Marker of Therapy Response in a Subset of Melanoma Patients","volume":"6","author":"Tetzlaff","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e359","DOI":"10.1111\/1346-8138.14887","article-title":"Sarcoid-like Reaction and Vitiligo Occurring after Nivolumab Therapy in a Patient with Metastatic Melanoma","volume":"46","author":"Fukuchi","year":"2019","journal-title":"J. Dermatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.ad.2017.11.021","article-title":"Granulomatous Reaction in a Patient with Metastatic Melanoma Treated with Ipilimumab: First Case Reported with Isolated Cutaneous Findings","volume":"110","author":"Cervantes","year":"2019","journal-title":"Actas Dermo-Sifiliogr\u00e1ficas"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e1068","DOI":"10.1097\/MJT.0000000000000266","article-title":"Ipilimumab-Induced Granulomatous Disease Occurring Simultaneously with Disease Progression in a Patient with Metastatic Melanoma","volume":"23","author":"Toumeh","year":"2016","journal-title":"Am. J. Ther."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/j.autrev.2018.01.003","article-title":"Rheumatic Manifestations among Cancer Patients Treated with Immune Checkpoint Inhibitors","volume":"17","author":"Lidar","year":"2018","journal-title":"Autoimmun. Rev."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1001\/jamadermatol.2017.0581","article-title":"Pembrolizumab-Induced Extensive Panniculitis and Nevus Regression: Two Novel Cutaneous Manifestations of the Post-Immunotherapy Granulomatous Reactions Spectrum","volume":"153","year":"2017","journal-title":"JAMA Dermatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e379","DOI":"10.1097\/MJT.0000000000000545","article-title":"Ipilimumab-Induced Sarcoidosis and Thyroiditis","volume":"25","author":"Nandavaram","year":"2018","journal-title":"Am. J. Ther."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s40425-018-0390-2","article-title":"Delayed Onset of Neurosarcoidosis after Concurrent Ipilimumab\/Nivolumab Therapy","volume":"6","author":"Tan","year":"2018","journal-title":"J. Immunother. Cancer"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1097\/RLU.0000000000002779","article-title":"18F-FDG PET\/CT of Multiorgan Sarcoid-Like Reaction During Anti-PD-1 Treatment for Melanoma","volume":"44","author":"Gerritsen","year":"2019","journal-title":"Clin. Nucl. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1001\/jamadermatol.2018.1912","article-title":"Timing of Onset of Adverse Cutaneous Reactions Associated with Programmed Cell Death Protein 1 Inhibitor Therapy","volume":"154","author":"Wang","year":"2018","journal-title":"JAMA Dermatol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1097\/DAD.0000000000001066","article-title":"Granulomatous Tumoral Melanosis Associated with Pembrolizumab Therapy: A Mimicker of Disease Progression in Metastatic Melanoma","volume":"40","author":"Woodbeck","year":"2018","journal-title":"Am. J. Dermatopathol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1183\/09031936.00107912","article-title":"Sarcoidosis Complicating Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody Biotherapy","volume":"41","author":"Tissot","year":"2013","journal-title":"Eur. Respir. J."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1177\/1078155216667635","article-title":"Sarcoidosis-like Syndrome and Lymphadenopathy Due to Checkpoint Inhibitors","volume":"23","author":"Firwana","year":"2017","journal-title":"J. Oncol. Pharm. Pract."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.humpath.2019.07.001","article-title":"Immune Checkpoint Blocker-Related Sarcoid-like Granulomatous Inflammation: A Rare Adverse Event Detected in Lymph Node Aspiration Cytology of Patients Treated for Advanced Malignant Melanoma","volume":"91","author":"Rodriguez","year":"2019","journal-title":"Hum. Pathol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ejca.2020.02.024","article-title":"Drug-Induced Sarcoidosis-like Reaction in Adjuvant Immunotherapy: Increased Rate and Mimicker of Metastasis","volume":"131","author":"Chorti","year":"2020","journal-title":"Eur. J. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1097\/CJI.0000000000000298","article-title":"Sarcoid-like Reaction Discovered on EBUS-TBNA of Intrathoracic Lymph Nodes During Immunotherapy for Metastatic Melanoma","volume":"43","author":"Frohlich","year":"2020","journal-title":"J. Immunother."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e519","DOI":"10.1097\/RLU.0000000000002724","article-title":"Nivolumab-Associated Pulmonary and Bone Sarcoidosis in a Patient With Melanoma of Unknown Primary","volume":"44","author":"Tulbah","year":"2019","journal-title":"Clin. Nucl. Med."},{"key":"ref_66","first-page":"S460","article-title":"Cutaneous and Pulmonary Sarcoid-Like Reaction Induced by Nivolumab: Case Report and Brief Literature Review","volume":"27","year":"2019","journal-title":"J. Clin. Rheumatol."},{"key":"ref_67","first-page":"255","article-title":"Subcutaneous Sarcoidosis Induced by Pembrolizumab in a Melanoma Patient Mimicking Subcutaneous Metastasis at 18F-FDG PET\/CT","volume":"40","author":"Marcoval","year":"2021","journal-title":"Rev. Esp. Med. Nucl. Imagen. Mol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e14618","DOI":"10.1111\/dth.14618","article-title":"Challenges in Sarcoidosis and Sarcoid-like Reactions Associated to Immune Checkpoint Inhibitors: A Narrative Review apropos of a Case","volume":"34","author":"Apalla","year":"2021","journal-title":"Dermatol. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1097\/CMR.0000000000000680","article-title":"An Atypical Sarcoid-like Reaction during Anti-Protein Death 1 Treatment in a Patient with Metastatic Melanoma","volume":"30","author":"Keukeleire","year":"2020","journal-title":"Melanoma Res."},{"key":"ref_70","first-page":"20190065","article-title":"Sarcoidosis-like Disease Mimicking Metastases during Adjuvant Ipilimumab Therapy in Advanced Melanoma Patient: CT Scan and MRI Help in Managing Difficult Clinical Decision","volume":"6","author":"Garanzini","year":"2020","journal-title":"BJR Case Rep."},{"key":"ref_71","first-page":"6702870","article-title":"Exclusive Cutaneous and Subcutaneous Sarcoidal Granulomatous Inflammation Due to Immune Checkpoint Inhibitors: Report of Two Cases with Unusual Manifestations and Review of the Literature","volume":"2019","author":"Mobini","year":"2019","journal-title":"Case Rep. Dermatol. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e240701","DOI":"10.1136\/bcr-2020-240701","article-title":"Is It Metastatic Melanoma or Is It Sarcoidosis? Non-Caseating Granulomas Due to Pembrolizumab","volume":"13","author":"Chahin","year":"2020","journal-title":"BMJ Case Rep."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Abdel-Wahab, N., Shah, M., and Suarez-Almazor, M.E. (2016). Adverse Events Associated with Immune Checkpoint Blockade in Patients with Cancer: A Systematic Review of Case Reports. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0160221"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"W992","DOI":"10.2214\/AJR.10.6198","article-title":"Radiologic Manifestations of Immune-Related Adverse Events in Patients with Metastatic Melanoma Undergoing Anti-CTLA-4 Antibody Therapy","volume":"197","author":"Bronstein","year":"2011","journal-title":"Am. J. Roentgenol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1158\/2326-6066.CIR-15-0102","article-title":"Radiographic Profiling of Immune-Related Adverse Events in Advanced Melanoma Patients Treated with Ipilimumab","volume":"3","author":"Tirumani","year":"2015","journal-title":"Cancer Immunol. Res."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"P103","DOI":"10.1186\/2051-1426-2-S3-P103","article-title":"Patterns of Response in Patients with Advanced Melanoma Treated with Pembrolizumab (MK-3475) and Evaluation of Immune-Related Response Criteria (IrRC)","volume":"2","author":"Hodi","year":"2014","journal-title":"J. ImmunoTherapy Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"30268","DOI":"10.18632\/oncotarget.25666","article-title":"Non-Invasive Visualization of Tumor Infiltrating Lymphocytes in Patients with Metastatic Melanoma Undergoing Immune Checkpoint Inhibitor Therapy: A Pilot Study","volume":"9","author":"Markovic","year":"2018","journal-title":"Oncotarget"},{"key":"ref_78","unstructured":"Statement on Sarcoidosis (1999). Joint Statement of the American Thoracic Society (ATS), the European Respiratory Society (ERS) and the World Association of Sarcoidosis and Other Granulomatous Disorders (WASOG) Adopted by the ATS Board of Directors and by the ERS Executive Committee, February 1999. Am. J. Respir. Crit. Care Med., 160, 736\u2013755."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"89","DOI":"10.12703\/P6-89","article-title":"Advances in the Diagnosis and Treatment of Sarcoidosis","volume":"6","author":"Judson","year":"2014","journal-title":"F1000Prime Rep"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"16065","DOI":"10.1073\/pnas.1417789111","article-title":"Mathematical Model of Sarcoidosis","volume":"111","author":"Hao","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1164\/rccm.201503-0418OC","article-title":"Identification of Immune-Relevant Factors Conferring Sarcoidosis Genetic Risk","volume":"192","author":"Fischer","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1080\/1744666X.2016.1181541","article-title":"Advances in Understanding the Immunopathology of Sarcoidosis and Implications on Therapy","volume":"12","author":"Cinetto","year":"2016","journal-title":"Expert Rev. Clin. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1136\/thx.2010.140319","article-title":"Sarcoidosis Is a Th1\/Th17 Multisystem Disorder","volume":"66","author":"Facco","year":"2011","journal-title":"Thorax"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1189\/jlb.0307133","article-title":"Expression and Role of CCR6\/CCL20 Chemokine Axis in Pulmonary Sarcoidosis","volume":"82","author":"Facco","year":"2007","journal-title":"J. Leukoc. Biol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1093\/abbs\/gmt049","article-title":"Recruitment of CCR6-Expressing Th17 Cells by CCL20 Secreted from Plasmin-Stimulated Macrophages","volume":"45","author":"Li","year":"2013","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1164\/rccm.201507-1499OC","article-title":"IFN-\u03b3-Producing T-Helper 17.1 Cells Are Increased in Sarcoidosis and Are More Prevalent than T-Helper Type 1 Cells","volume":"193","author":"Ramstein","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"21463","DOI":"10.3390\/ijms141121463","article-title":"Imbalance between Th17 and Regulatory T-Cells in Sarcoidosis","volume":"14","author":"Huang","year":"2013","journal-title":"Int. J. Mol. Sci."},{"key":"ref_88","first-page":"334","article-title":"The Roles of T Helper 1, T Helper 17 and Regulatory T Cells in the Pathogenesis of Sarcoidosis","volume":"15","author":"Mortaz","year":"2016","journal-title":"Iran. J. Allergy Asthma Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"S429","DOI":"10.1513\/AnnalsATS.201707-565OT","article-title":"Genetic, Immunologic, and Environmental Basis of Sarcoidosis","volume":"14","author":"Moller","year":"2017","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1016\/j.jtho.2018.04.031","article-title":"Sarcoidosis-Like Reactions Induced by Checkpoint Inhibitors","volume":"13","author":"Gkiozos","year":"2018","journal-title":"J. Thorac. Oncol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.4049\/jimmunol.0903369","article-title":"Cutting Edge: CTLA-4\u2013B7 Interaction Suppresses Th17 Cell Differentiation","volume":"185","author":"Ying","year":"2010","journal-title":"J. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/1479-5876-7-35","article-title":"CTLA4 Blockade Increases Th17 Cells in Patients with Metastatic Melanoma","volume":"7","author":"Chodon","year":"2009","journal-title":"J. Transl. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1164\/rccm.201503-0635LE","article-title":"Decreased Cytotoxic T-Lymphocyte Antigen 4 Expression on Regulatory T Cells and Th17 Cells in Sarcoidosis: Double Trouble?","volume":"192","author":"Broos","year":"2015","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"9543","DOI":"10.1128\/MCB.25.21.9543-9553.2005","article-title":"CTLA-4 and PD-1 Receptors Inhibit T-Cell Activation by Distinct Mechanisms","volume":"25","author":"Parry","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4530","DOI":"10.4049\/jimmunol.1002031","article-title":"The Link between the PDL1 Costimulatory Pathway and Th17 in Fetomaternal Tolerance","volume":"187","author":"Riella","year":"2011","journal-title":"J. Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1038\/cmi.2017.70","article-title":"The Altered PD-1\/PD-L1 Pathway Delivers the \u2018One-Two Punch\u2019 Effects to Promote the Treg\/Th17 Imbalance in Pre-Eclampsia","volume":"15","author":"Zhang","year":"2018","journal-title":"Cell. Mol. Immunol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1164\/rccm.201512-2419ED","article-title":"Sarcoidosis and T-Helper Cells. Th1, Th17, or Th17.1?","volume":"193","author":"Georas","year":"2016","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/rheumatology\/ker316","article-title":"Increased IL-17A Expression in Granulomas and in Circulating Memory T Cells in Sarcoidosis","volume":"51","author":"Paats","year":"2012","journal-title":"Rheumatology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1111\/1756-185X.13076","article-title":"Immunotherapy-Induced Sarcoidosis in Patients with Melanoma Treated with PD-1 Checkpoint Inhibitors: Case Series and Immunophenotypic Analysis","volume":"20","author":"Lomax","year":"2017","journal-title":"Int. J. Rheum. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/ni.3655","article-title":"Chronic Signaling via the Metabolic Checkpoint Kinase MTORC1 Induces Macrophage Granuloma Formation and Marks Sarcoidosis Progression","volume":"18","author":"Linke","year":"2017","journal-title":"Nat. Immunol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/12\/2937\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:31:26Z","timestamp":1760139086000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/12\/2937"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,14]]},"references-count":100,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["cancers14122937"],"URL":"https:\/\/doi.org\/10.3390\/cancers14122937","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,14]]}}}