{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T14:41:31Z","timestamp":1790260891573,"version":"4.1.0"},"reference-count":56,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T00:00:00Z","timestamp":1599004800000},"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. Oncol."],"DOI":"10.3389\/fonc.2020.01361","type":"journal-article","created":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T00:28:29Z","timestamp":1599006509000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Enhanced Anticancer Effect of a Combination of S-adenosylmethionine (SAM) and Immune Checkpoint Inhibitor (ICPi) in a Syngeneic Mouse Model of Advanced Melanoma"],"prefix":"10.3389","volume":"10","author":[{"given":"Ali","family":"Mehdi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikhael","family":"Attias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niaz","family":"Mahmood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ani","family":"Arakelian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalin","family":"Mihalcioiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ciriaco A.","family":"Piccirillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moshe","family":"Szyf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shafaat Ahmed","family":"Rabbani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,9,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/S0140-6736(18)31559-9","article-title":"Melanoma","volume":"392","author":"Schadendorf","year":"2018","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e12964","DOI":"10.1111\/dth.12964","article-title":"Current insights into the epigenetic mechanisms of skin cancer","volume":"32","author":"Sang","year":"2019","journal-title":"Dermatol Ther"},{"key":"B3","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/301089a0","article-title":"Hypomethylation distinguishes genes of some human cancers from their normal counterparts","volume":"301","author":"Feinberg","year":"1983","journal-title":"Nature"},{"key":"B4","doi-asserted-by":"publisher","first-page":"239","DOI":"10.2217\/epi.09.33","article-title":"DNA hypomethylation in cancer cells","volume":"1","author":"Ehrlich","year":"2009","journal-title":"Epigenomics"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1151s","DOI":"10.1093\/ajcn\/76.5.1151S","article-title":"S-Adenosyl-L-methionine (SAMe): from the bench to the bedside\u2013molecular basis of a pleiotrophic molecule","volume":"76","author":"Bottiglieri","year":"2002","journal-title":"Am J Clin Nutr"},{"key":"B6","doi-asserted-by":"publisher","first-page":"5169","DOI":"10.18632\/oncotarget.23704","article-title":"Methyl donor S-adenosylmethionine (SAM) supplementation attenuates breast cancer growth, invasion, and metastasis in vivo; therapeutic and chemopreventive applications","volume":"9","author":"Mahmood","year":"2018","journal-title":"Oncotarget"},{"key":"B7","doi-asserted-by":"publisher","first-page":"31735","DOI":"10.1074\/jbc.M401669200","article-title":"Reversal of the hypomethylation status of urokinase (uPA) promoter blocks breast cancer growth and metastasis","volume":"279","author":"Pakneshan","year":"2004","journal-title":"J Biol Chem"},{"key":"B8","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1002\/cam4.386","article-title":"S-adenosylmethionine blocks osteosarcoma cells proliferation and invasion in vitro and tumor metastasis in vivo: therapeutic and diagnostic clinical applications","volume":"4","author":"Parashar","year":"2015","journal-title":"Cancer Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"2769","DOI":"10.1111\/bph.13102","article-title":"Pharmacological methyl group donors block skeletal metastasis in vitro and in vivo","volume":"172","author":"Shukeir","year":"2015","journal-title":"Br J Pharmacol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1007\/978-3-030-22254-3_14","article-title":"Targeting DNA hypomethylation in malignancy by epigenetic therapies","volume":"1164","author":"Mahmood","year":"2019","journal-title":"Adv Exp Med Biol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.bbrc.2011.03.138","article-title":"Inhibition of angiogenesis by S-adenosylmethionine","volume":"408","author":"Sahin","year":"2011","journal-title":"Biochem Biophys Res Commun."},{"key":"B12","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1093\/carcin\/bgr295","article-title":"Effects of S-adenosylmethionine and methylthioadenosine on inflammation-induced colon cancer in mice","volume":"33","author":"Li","year":"2012","journal-title":"Carcinogenesis."},{"key":"B13","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1042\/bj3190929","article-title":"Interleukin-2 induces gamma-S-adenosyl-L-methionine synthetase gene expression during T-lymphocyte activation","volume":"319","author":"Tobena","year":"1996","journal-title":"Biochem J."},{"key":"B14","doi-asserted-by":"publisher","first-page":"16040","DOI":"10.1074\/jbc.272.25.16040","article-title":"Differential regulation of methionine adenosyltransferase in superantigen and mitogen stimulated human T lymphocytes","volume":"272","author":"Legros","year":"1997","journal-title":"J Biol Chem"},{"key":"B15","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1042\/bj3530163","article-title":"The role of c-Myb in the up-regulation of methionine adenosyltransferase 2A expression in activated Jurkat cells","volume":"353","author":"Zeng","year":"2001","journal-title":"Biochem J"},{"key":"B16","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1016\/j.jnutbio.2007.05.010","article-title":"Ethanol inhibits methionine adenosyltransferase II activity and S-adenosylmethionine biosynthesis and enhances caspase-3-dependent cell death in T lymphocytes: relevance to alcohol-induced immunosuppression","volume":"19","author":"Hote","year":"2008","journal-title":"J Nutr Biochem"},{"key":"B17","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1038\/nm730","article-title":"Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion","volume":"8","author":"Dong","year":"2002","journal-title":"Nat Med"},{"key":"B18","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1038\/nrc3239","article-title":"The blockade of immune checkpoints in cancer immunotherapy","volume":"12","author":"Pardoll","year":"2012","journal-title":"Nature Reviews Cancer"},{"key":"B19","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.febslet.2004.07.083","article-title":"PD-1 inhibits T-cell receptor induced phosphorylation of the ZAP70\/CD3zeta signalosome and downstream signaling to PKCtheta","volume":"574","author":"Sheppard","year":"2004","journal-title":"FEBS Lett"},{"key":"B20","doi-asserted-by":"publisher","first-page":"561","DOI":"10.3389\/fphar.2017.00561","article-title":"PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: mechanism, combinations, and clinical outcome","volume":"8","author":"Alsaab","year":"2017","journal-title":"Front Pharmacol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"2443","DOI":"10.1056\/NEJMoa1200690","article-title":"Safety, activity, and immune correlates of anti-PD-1 antibody in cancer","volume":"366","author":"Topalian","year":"2012","journal-title":"N Engl J Med"},{"key":"B22","doi-asserted-by":"publisher","first-page":"873","DOI":"10.1634\/theoncologist.2016-0496","article-title":"FDA approval summary: pembrolizumab for the treatment of recurrent or metastatic head and neck squamous cell carcinoma with disease progression on or after platinum-containing chemotherapy","volume":"22","author":"Larkins","year":"2017","journal-title":"Oncologist"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1158\/0008-5472.CAN-15-2125","article-title":"Combining epigenetic and immunotherapy to combat cancer","volume":"76","author":"Chiappinelli","year":"2016","journal-title":"Cancer Res"},{"key":"B24","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/j.molimm.2017.04.012","article-title":"Epigenetics and immunotherapy: the current state of play","volume":"87","author":"Dunn","year":"2017","journal-title":"Mol Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"5370","DOI":"10.1158\/0008-5472.CAN-04-0788","article-title":"A synthetic 15-mer peptide (PCK3145) derived from prostate secretory protein can reduce tumor growth, experimental skeletal metastases, and malignancy-associated hypercalcemia","volume":"64","author":"Shukeir","year":"2004","journal-title":"Cancer Res"},{"key":"B26","doi-asserted-by":"publisher","first-page":"10557","DOI":"10.18632\/oncotarget.7235","article-title":"Activation of the PD-1\/PD-L1 immune checkpoint confers tumor cell chemoresistance associated with increased metastasis","volume":"7","author":"Black","year":"2016","journal-title":"Oncotarget"},{"key":"B27","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1158\/2326-6066.CIR-14-0040","article-title":"In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates","volume":"2","author":"Wang","year":"2014","journal-title":"Cancer Immunol Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"2375","DOI":"10.1093\/annonc\/mdv383","article-title":"Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies","volume":"26","author":"Naidoo","year":"2015","journal-title":"Ann Oncol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1402","DOI":"10.1038\/nm.4200","article-title":"Eradication of large established tumors in mice by combination immunotherapy that engages innate and adaptive immune responses","volume":"22","author":"Moynihan","year":"2016","journal-title":"Nat Med"},{"key":"B30","doi-asserted-by":"publisher","first-page":"2256","DOI":"10.1038\/s41467-017-02358-7","article-title":"TNFalpha blockade overcomes resistance to anti-PD-1 in experimental melanoma","volume":"8","author":"Bertrand","year":"2017","journal-title":"Nat Commun"},{"key":"B31","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1038\/nbt.4180","article-title":"Reversal of indoleamine 2,3-dioxygenase-mediated cancer immune suppression by systemic kynurenine depletion with a therapeutic enzyme","volume":"36","author":"Triplett","year":"2018","journal-title":"Nat Biotechnol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1016\/j.ebiom.2019.08.067","article-title":"Role of CXCR3 signaling in response to anti-PD-1 therapy","volume":"48","author":"Han","year":"2019","journal-title":"EBioMedicine"},{"key":"B33","doi-asserted-by":"publisher","first-page":"401","DOI":"10.3892\/ijo.2011.1040","article-title":"A KDR-binding peptide (ST100,059) can block angiogenesis, melanoma tumor growth and metastasis in vitro and in vivo","volume":"39","author":"Rastelli","year":"2011","journal-title":"Int J Oncol"},{"key":"B34","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1002\/eji.201970107","article-title":"Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)","volume":"49","author":"Cossarizza","year":"2019","journal-title":"Eur J Immunol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"D712","DOI":"10.1093\/nar\/gkq1156","article-title":"ConsensusPathDB: toward a more complete picture of cell biology","volume":"39","author":"Kamburov","year":"2011","journal-title":"Nucleic Acids Res"},{"key":"B37","doi-asserted-by":"publisher","first-page":"386","DOI":"10.3389\/fonc.2018.00386","article-title":"Tumor-intrinsic PD-L1 signaling in cancer initiation, development and treatment: beyond immune evasion","volume":"8","author":"Dong","year":"2018","journal-title":"Front Oncol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/s41392-018-0022-9","article-title":"The intracellular signalosome of PD-L1 in cancer cells","volume":"3","author":"Escors","year":"2018","journal-title":"Signal Transduct Target Ther."},{"key":"B39","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1002\/0471142735.im2001s39","article-title":"B16 as a mouse model for human melanoma","volume":"39","author":"Overwijk","year":"2001","journal-title":"Curr Protoc Immunol Chapter"},{"key":"B40","doi-asserted-by":"publisher","first-page":"81","DOI":"10.4137\/CGM.S21214","article-title":"Current state of animal (Mouse) modeling in melanoma research","volume":"8","year":"2015","journal-title":"Cancer Growth Metastasis"},{"key":"B41","doi-asserted-by":"publisher","first-page":"bav097","DOI":"10.1093\/database\/bav097","article-title":"MGDB: a comprehensive database of genes involved in melanoma","volume":"2015","author":"Zhang","year":"2015","journal-title":"Database."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1016\/j.cell.2015.05.044","article-title":"Genomic classification of cutaneous melanoma","volume":"161","year":"2015","journal-title":"Cell"},{"key":"B43","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1158\/2159-8290.CD-12-0095","article-title":"The cBio cancer genomics portal: an open platform for exploring multidimensional cancer genomics data","volume":"2","author":"Cerami","year":"2012","journal-title":"Cancer Discov"},{"key":"B44","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1038\/s41587-020-0546-8","article-title":"Visualizing and interpreting cancer genomics data via the Xena platform","volume":"38","author":"Goldman","year":"2020","journal-title":"Nat Biotechnol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.humpath.2011.05.008","article-title":"Neuropilin-2: a novel biomarker for malignant melanoma?","volume":"43","author":"Rushing","year":"2012","journal-title":"Hum Pathol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1097\/CMR.0000000000000190","article-title":"Neuropilin-2 promotes melanoma growth and progression in vivo","volume":"26","author":"Moriarty","year":"2016","journal-title":"Melanoma Res"},{"key":"B47","unstructured":"DMBT1 encodes a protein involved in the immune defense and in epithelial differentiation and is highly unstable in cancer170410\n            MollenhauerJ\n            HerbertzS\n            HolmskovU\n            TolnayM\n            KrebsI\n            MerloA\n          10749143Cancer Res602000"},{"key":"B48","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1038\/nchembio.1204","article-title":"NNMT promotes epigenetic remodeling in cancer by creating a metabolic methylation sink","volume":"9","author":"Ulanovskaya","year":"2013","journal-title":"Nat Chem Biol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"e1067745","DOI":"10.1080\/2162402X.2015.1067745","article-title":"Long-lasting multifunctional CD8(+) T cell responses in end-stage melanoma patients can be induced by dendritic cell vaccination","volume":"5","author":"Wimmers","year":"2016","journal-title":"Oncoimmunology"},{"key":"B50","doi-asserted-by":"publisher","first-page":"857","DOI":"10.3389\/fonc.2019.00857","article-title":"Down regulation of c-FLIPL enhance PD-1 blockade efficacy in B16 melanoma","volume":"9","author":"Wang","year":"2019","journal-title":"Front Oncol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"4275","DOI":"10.1073\/pnas.0915174107","article-title":"PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors","volume":"107","author":"Curran","year":"2010","journal-title":"Proc Natl Acad Sci USA"},{"key":"B52","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1038\/mt.2015.156","article-title":"Combination therapy with reovirus and Anti-PD-1 blockade controls tumor growth through innate and adaptive immune responses","volume":"24","author":"Rajani","year":"2016","journal-title":"Mol Ther"},{"key":"B53","doi-asserted-by":"publisher","first-page":"e122700","DOI":"10.1172\/jci.insight.122700","article-title":"Targeting antigen-presenting cells by anti-PD-1 nanoparticles augments antitumor immunity","volume":"3","author":"Ordikhani","year":"2018","journal-title":"JCI Insight"},{"key":"B54","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1186\/s13046-019-1420-8","article-title":"Targeting CXCR4 potentiates anti-PD-1 efficacy modifying the tumor microenvironment and inhibiting neoplastic PD-1","volume":"38","author":"D'alterio","year":"2019","journal-title":"J Exp Clin Cancer Res"},{"key":"B55","doi-asserted-by":"publisher","first-page":"450","DOI":"10.3390\/cancers11040450","article-title":"Blockade of lactate dehydrogenase-A (LDH-A) improves efficacy of anti-programmed cell death-1 (PD-1) therapy in melanoma","volume":"11","author":"Daneshmandi","year":"2019","journal-title":"Cancers."},{"key":"B56","doi-asserted-by":"publisher","first-page":"111866","DOI":"10.18632\/oncotarget.22942","article-title":"S-adenosyl-methionine (SAM) alters the transcriptome and methylome and specifically blocks growth and invasiveness of liver cancer cells","volume":"8","author":"Wang","year":"2017","journal-title":"Oncotarget"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fonc.2020.01361\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,9,2]],"date-time":"2020-09-02T00:28:32Z","timestamp":1599006512000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fonc.2020.01361\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,2]]},"references-count":56,"alternative-id":["10.3389\/fonc.2020.01361"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2020.01361","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,2]]},"article-number":"1361"}}