{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:58:06Z","timestamp":1792789086674,"version":"4.5.0"},"reference-count":43,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100013700","name":"National Comprehensive Cancer Network","doi-asserted-by":"publisher","award":["2021-IST-DECC-000076"],"award-info":[{"award-number":["2021-IST-DECC-000076"]}],"id":[{"id":"10.13039\/100013700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013700","name":"National Comprehensive Cancer Network","doi-asserted-by":"publisher","award":["NCCNYIA22021"],"award-info":[{"award-number":["NCCNYIA22021"]}],"id":[{"id":"10.13039\/100013700","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2021-IST-DECC-000076"],"award-info":[{"award-number":["2021-IST-DECC-000076"]}],"id":[{"id":"https:\/\/ror.org\/0465x5x63","id-type":"ROR","asserted-by":"publisher"}]},{"award":["NCCNYIA22021"],"award-info":[{"award-number":["NCCNYIA22021"]}],"id":[{"id":"https:\/\/ror.org\/0465x5x63","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Patten-Davis Foundation","id":[{"id":"https:\/\/ror.org\/02mkdtg06","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/02mkdtg06","id-type":"ROR","asserted-by":"publisher"}]},{"name":"NIH\/NCI Cancer Center","award":["P30CA046934"],"award-info":[{"award-number":["P30CA046934"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Mucosal melanoma is a rare, aggressive melanoma subtype with lower response rates to immune checkpoint inhibitors than cutaneous melanoma. We previously identified reduced expression of innate immune pathogen-sensing pathway genes in mucosal melanoma, including components of the retinoic acid-inducible gene-I (RIG-I) pathway, and found that decitabine can induce re-expression of these immune genes and tumor-associated antigens. This study evaluated epigenetic immune priming with oral decitabine\/cedazuridine (DEC-C) combined with nivolumab in patients with unresectable or metastatic mucosal melanoma. Methods: NCT05089370 was an open-label, single-center, single-arm phase Ib\/II trial. Patients received DEC-C (35 mg decitabine\/100 mg cedazuridine) orally for five days followed by nivolumab 480 mg every four weeks. The primary endpoint was safety and determination of the recommended phase II dose (RP2D). Secondary endpoints included objective response rate (ORR) and survival outcomes. Exploratory endpoints assessed immune and epigenetic correlates. Results: Eight patients were enrolled. Treatment-related adverse events occurred in seven patients (88%), with dose-limiting toxicities observed in three (38%). The RP2D was not established due to premature trial closure. At data cut-off, two patients remained on treatment with ongoing partial responses. The ORR was 25% (95% CI, 3.2\u201365), median progression-free survival was 3.0 months (95% CI, 2.1\u2013not reached), and median overall survival was 7.2 months (95% CI, 4.4\u2013not reached). Treatment significantly decreased global DNA methylation and induced RIG-I pathway genes in circulating immune cells. Conclusions: DEC-C plus nivolumab was associated with frequent treatment-related toxicities consistent with the known safety profiles of decitabine and nivolumab and demonstrated on-target epigenetic and immune activity in circulating cells. Although two partial responses were observed, the small sample size and wide confidence interval preclude conclusions regarding efficacy. These findings support future biomarker-integrated studies evaluating epigenetic immune-priming combinations in mucosal melanoma, with prospective optimization of dose, schedule, and treatment setting.<\/jats:p>","DOI":"10.3390\/cancers18193172","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:43:24Z","timestamp":1790880204000},"page":"3172","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epigenetic Priming with Oral Decitabine\/Cedazuridine Combined with Nivolumab in Unresectable or Metastatic Mucosal Melanoma: Clinical and Correlative Findings from a Phase Ib\/II Trial"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6478-7821","authenticated-orcid":false,"given":"Jessica S. W.","family":"Borgers","sequence":"first","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2539-6860","authenticated-orcid":false,"given":"Cheng-Chang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, University of Colorado Cancer Center Biostatistics Core, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Theresa M.","family":"Medina","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Claire M.","family":"Muckle","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth N.","family":"Katsnelson","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phaedra A.","family":"Whitty","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0239-7032","authenticated-orcid":false,"given":"Luke","family":"Mantle","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Sapna P.","family":"Patel","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"},{"name":"Department of Ophthalmology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3920-7060","authenticated-orcid":false,"given":"Dexiang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, University of Colorado Cancer Center Biostatistics Core, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8380-7157","authenticated-orcid":false,"given":"Kimberly R.","family":"Jordan","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"William A.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Richard P.","family":"Tobin","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8174-1713","authenticated-orcid":false,"given":"Martin D.","family":"McCarter","sequence":"additional","affiliation":[{"name":"Division of Surgical Oncology, Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2088-2229","authenticated-orcid":false,"given":"Kasey L.","family":"Couts","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1664","DOI":"10.1002\/(SICI)1097-0142(19981015)83:8<1664::AID-CNCR23>3.0.CO;2-G","article-title":"The National Cancer Data Base report on cutaneous and noncutaneous melanoma: A summary of 84,836 cases from the past decade. The American College of Surgeons Commission on Cancer and the American Cancer Society","volume":"83","author":"Chang","year":"1998","journal-title":"Cancer"},{"key":"ref_2","first-page":"739","article-title":"Primary mucosal melanomas: A comprehensive review","volume":"5","author":"Mihajlovic","year":"2012","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"848","DOI":"10.1634\/theoncologist.2015-0522","article-title":"Prognosis of Mucosal, Uveal, Acral, Nonacral Cutaneous, and Unknown Primary Melanoma from the Time of First Metastasis","volume":"21","author":"Kuk","year":"2016","journal-title":"Oncologist"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1200\/JCO.2016.67.9258","article-title":"Efficacy and Safety of Nivolumab Alone or in Combination with Ipilimumab in Patients with Mucosal Melanoma: A Pooled Analysis","volume":"35","author":"Larkin","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"3354","DOI":"10.1002\/cncr.30259","article-title":"The efficacy of anti-PD-1 agents in acral and mucosal melanoma","volume":"122","author":"Shoushtari","year":"2016","journal-title":"Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1634\/theoncologist.2012-0464","article-title":"Ipilimumab for patients with advanced mucosal melanoma","volume":"18","author":"Postow","year":"2013","journal-title":"Oncologist"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"582","DOI":"10.1093\/annonc\/mdz011","article-title":"Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001","volume":"30","author":"Hamid","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_8","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_9","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.ejca.2018.09.025","article-title":"Efficacy and safety of nivolumab in combination with ipilimumab in Japanese patients with advanced melanoma: An open-label, single-arm, multicentre phase II study","volume":"105","author":"Namikawa","year":"2018","journal-title":"Eur. J. Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/s41416-018-0207-6","article-title":"Antitumour activity of pembrolizumab in advanced mucosal melanoma: A post-hoc analysis of KEYNOTE-001, 002, 006","volume":"119","author":"Hamid","year":"2018","journal-title":"Br. J. Cancer"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1007\/s10147-020-01618-9","article-title":"Multicenter prospective phase II trial of nivolumab in patients with unresectable or metastatic mucosal melanoma","volume":"25","author":"Nomura","year":"2020","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.1200\/JCO.19.01464","article-title":"Long-Term Outcomes and Responses to Retreatment in Patients with Melanoma Treated with PD-1 Blockade","volume":"38","author":"Palmer","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"MacBeth, M.L., Bagby, S.M., Borgers, J.S.W., Turner, J.A., Anderson, K.C., Whitty, P.A., Hartman, S.J., Yacob, B., Rebecca, V.W., and Davila, E. (2026). Decitabine reverses innate immune gene suppression in rare melanomas. Mol. Cancer Ther., OF1\u2013OF12.","DOI":"10.1158\/1535-7163.MCT-25-1325"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e1570779","DOI":"10.1080\/2162402X.2019.1570779","article-title":"Targeting intrinsic RIG-I signaling turns melanoma cells into type I interferon-releasing cellular antitumor vaccines","volume":"8","author":"Bek","year":"2019","journal-title":"Oncoimmunology"},{"key":"ref_15","first-page":"4266","article-title":"Targeting the innate immunoreceptor RIG-I overcomes melanoma-intrinsic resistance to T cell immunotherapy","volume":"130","author":"Such","year":"2020","journal-title":"J. Clin. Investig."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"eaau8943","DOI":"10.1126\/sciimmunol.aau8943","article-title":"RIG-I activation is critical for responsiveness to checkpoint blockade","volume":"4","author":"Heidegger","year":"2019","journal-title":"Sci. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Fazio, C., Covre, A., Cutaia, O., Lofiego, M.F., Tunici, P., Chiarucci, C., Cannito, S., Giacobini, G., Lowder, J.N., and Ferraldeschi, R. (2018). Immunomodulatory Properties of DNA Hypomethylating Agents: Selecting the Optimal Epigenetic Partner for Cancer Immunotherapy. Front. Pharmacol., 9.","DOI":"10.3389\/fphar.2018.01443"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1016\/j.cell.2015.07.011","article-title":"Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses","volume":"162","author":"Chiappinelli","year":"2015","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1093\/annonc\/mds591","article-title":"Safety and efficacy of decitabine in combination with temozolomide in metastatic melanoma: A phase I\/II study and pharmacokinetic analysis","volume":"24","author":"Tawbi","year":"2013","journal-title":"Ann. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"7351","DOI":"10.1158\/1078-0432.CCR-19-1335","article-title":"Guadecitabine Plus Ipilimumab in Unresectable Melanoma: The NIBIT-M4 Clinical Trial","volume":"25","author":"Covre","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1007\/s40265-020-01389-7","article-title":"Decitabine\/Cedazuridine: First Approval","volume":"80","author":"Dhillon","year":"2020","journal-title":"Drugs"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2582","DOI":"10.1021\/jm401856k","article-title":"Design, synthesis, and pharmacological evaluation of fluorinated tetrahydrouridine derivatives as inhibitors of cytidine deaminase","volume":"57","author":"Ferraris","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e194","DOI":"10.1016\/S2352-3026(19)30030-4","article-title":"An oral fixed-dose combination of decitabine and cedazuridine in myelodysplastic syndromes: A multicentre, open-label, dose-escalation, phase 1 study","volume":"6","author":"Savona","year":"2019","journal-title":"Lancet Haematol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"TPS3183","DOI":"10.1200\/JCO.2025.43.16_suppl.TPS3183","article-title":"A phase I\/Ib study of olaparib and ASTX727 in BRCA 1\/2- and HRD-mutated tumors","volume":"43","author":"Munster","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e1367","DOI":"10.1002\/cti2.1367","article-title":"Circulating CD8(+) mucosal-associated invariant T cells correlate with improved treatment responses and overall survival in anti-PD-1-treated melanoma patients","volume":"11","author":"Vorwald","year":"2022","journal-title":"Clin. Transl. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1158\/2326-6066.CIR-18-0637","article-title":"CD96 Is an Immune Checkpoint That Regulates CD8(+) T-cell Antitumor Function","volume":"7","author":"Mittal","year":"2019","journal-title":"Cancer Immunol. Res."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Ma, W., Wei, S., Long, S., Tian, E.C., McLaughlin, B., Jaimes, M., Montoya, D.J., Viswanath, V.R., Chien, J., and Zhang, Q. (2023). Dynamic evaluation of blood immune cells predictive of response to immune checkpoint inhibitors in NSCLC by multicolor spectrum flow cytometry. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1206631"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1038\/s41591-024-03418-4","article-title":"Personalized, autologous neoantigen-specific T cell therapy in metastatic melanoma: A phase 1 trial","volume":"31","author":"Borgers","year":"2025","journal-title":"Nat. Med."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Tobin, R.P., Jordan, K.R., Kapoor, P., Spongberg, E., Davis, D., Vorwald, V.M., Couts, K.L., Gao, D., Smith, D.E., and Borgers, J.S.W. (2019). IL-6 and IL-8 Are Linked with Myeloid-Derived Suppressor Cell Accumulation and Correlate with Poor Clinical Outcomes in Melanoma Patients. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.01223"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1158\/1078-0432.CCR-22-2495","article-title":"Targeting MDSC Differentiation Using ATRA: A Phase I\/II Clinical Trial Combining Pembrolizumab and All-Trans Retinoic Acid for Metastatic Melanoma","volume":"29","author":"Tobin","year":"2023","journal-title":"Clin. Cancer Res."},{"key":"ref_31","unstructured":"(2026, August 01). INQOVI FDA Prescibing Information, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/212576s003lbl.pdf."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1056\/NEJMoa2407417","article-title":"Final, 10-Year Outcomes with Nivolumab plus Ipilimumab in Advanced Melanoma","volume":"392","author":"Wolchok","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1056\/NEJMoa2109970","article-title":"Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma","volume":"386","author":"Tawbi","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"542","DOI":"10.1111\/pcmr.13139","article-title":"Proceedings from the Melanoma Research Foundation Mucosal Melanoma Meeting (December 16, 2022, New York, USA)","volume":"36","author":"Wei","year":"2023","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e004495","DOI":"10.1136\/jitc-2022-004495","article-title":"Phase 1, dose-escalation study of guadecitabine (SGI-110) in combination with pembrolizumab in patients with solid tumors","volume":"10","author":"Yuan","year":"2022","journal-title":"J. Immunother. Cancer"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1200\/JCO.18.02151","article-title":"Addition of Low-Dose Decitabine to Anti-PD-1 Antibody Camrelizumab in Relapsed\/Refractory Classical Hodgkin Lymphoma","volume":"37","author":"Nie","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_37","unstructured":"(2026, January 01). OPDIVO FDA Prescibing Information, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/125554s112lbl.pdf."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1172\/JCI45138","article-title":"Allograft rejection is restrained by short-lived TIM-3+PD-1+Foxp3+ Tregs","volume":"122","author":"Gupta","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Gao, X., Zhu, Y., Li, G., Huang, H., Zhang, G., Wang, F., Sun, J., Yang, Q., Zhang, X., and Lu, B. (2012). TIM-3 expression characterizes regulatory T cells in tumor tissues and is associated with lung cancer progression. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0030676"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1002\/jso.24012","article-title":"T-cell immunoglobulin mucin-3 expression in bladder urothelial carcinoma: Clinicopathologic correlations and association with survival","volume":"112","author":"Yang","year":"2015","journal-title":"J. Surg. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Huang, L., Xu, Y., Fang, J., Liu, W., Chen, J., Liu, Z., and Xu, Q. (2021). Targeting STAT3 Abrogates Tim-3 Upregulation of Adaptive Resistance to PD-1 Blockade on Regulatory T Cells of Melanoma. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.654749"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.intimp.2018.08.007","article-title":"Targeting myeloid-derived suppressor cells using all-trans retinoic acid in melanoma patients treated with Ipilimumab","volume":"63","author":"Tobin","year":"2018","journal-title":"Int. Immunopharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e179982","DOI":"10.1172\/jci.insight.179982","article-title":"Diversity of the immune microenvironment and response to checkpoint inhibitor immunotherapy in mucosal melanoma","volume":"9","author":"Vos","year":"2024","journal-title":"JCI Insight"}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/19\/3172\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:46:42Z","timestamp":1790880402000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/19\/3172"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":43,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["cancers18193172"],"URL":"https:\/\/doi.org\/10.3390\/cancers18193172","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,1]]}}}