DNA methylation of GITR, OX40, 4-1BB, CD27 , and CD40 correlates with BAP1 aberrancy and prognosis in uveal melanoma.
Journal
Melanoma research
ISSN: 1473-5636
Titre abrégé: Melanoma Res
Pays: England
ID NLM: 9109623
Informations de publication
Date de publication:
01 04 2023
01 04 2023
Historique:
pubmed:
4
2
2023
medline:
25
2
2023
entrez:
3
2
2023
Statut:
ppublish
Résumé
Uveal melanoma represents an aggressive tumor that responds mostly poorly to established melanoma treatments. Comprehensive methylation profiling of the next-generation immunotherapeutic target genes, for example, members of the tumor necrosis factor receptor superfamily, might allow for the development of companion predictive biomarkers. We have analyzed CpG sites within the immune checkpoint genes GITR, OX40, 4-1BB, CD 27, and CD40 probed by the Illumina Infinium HumanMethylation450 BeadChip in N = 80 uveal melanomas included in The Cancer Genome Atlas with regard to BAP1 aberrancy, mRNA expression, and overall survival. In all analyzed immune checkpoint genes, BAP1 aberrancy was associated with decreased CpG methylation levels. We identified specific CpG sites that significantly correlated with BAP1 aberrancy, mRNA expression levels, and overall survival. Our results suggest epigenetic regulation of the analyzed immune checkpoint genes via DNA methylation in uveal melanoma and provide rationale for methylation testing in biomarker programs in clinical trials.
Identifiants
pubmed: 36735464
doi: 10.1097/CMR.0000000000000879
pii: 00008390-202304000-00003
doi:
Substances chimiques
BAP1 protein, human
0
RNA, Messenger
0
Tumor Suppressor Proteins
0
Ubiquitin Thiolesterase
EC 3.4.19.12
TNFRSF18 protein, human
0
TNFRSF4 protein, human
0
Tumor Necrosis Factor Receptor Superfamily, Member 7
0
CD40 Antigens
0
TNFRSF9 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
116-125Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Références
Kujala E, Mäkitie T, Kivelä T. Very long-term prognosis of patients with malignant uveal melanoma. Invest Ophthalmol Vis Sci 2003; 44:4651–4659.
Diener-West M, Reynolds SM, Agugliaro DJ, Caldwell R, Cumming K, Earle JD, et al. Development of metastatic disease after enrollment in the COMS trials for treatment of choroidal melanoma: Collaborative Ocular Melanoma Study Group Report No. 26. Arch Ophthalmol 2005; 123:1639–1643.
Heppt MV, Heinzerling L, Kähler KC, Forschner A, Kirchberger MC, Loquai C, et al. Prognostic factors and outcomes in metastatic uveal melanoma treated with programmed cell death-1 or combined PD-1/cytotoxic T-lymphocyte antigen-4 inhibition. Eur J Cancer 2017; 82:56–65.
Piulats JM, Espinosa E, de la Cruz Merino L, Varela M, Alonso Carrión L, Martín-Algarra S, et al. Nivolumab plus ipilimumab for treatment-naïve metastatic uveal melanoma: an open-label, multicenter, phase II trial by the Spanish Multidisciplinary Melanoma Group (GEM-1402). J Clin Oncol 2021; 39:586–598.
Nathan P, Hassel JC, Rutkowski P, Baurain J-F, Butler MO, Schlaak M, et al. Overall survival benefit with tebentafusp in metastatic uveal melanoma. N Engl J Med 2021; 385:1196–1206.
Croft M. The role of TNF superfamily members in T-cell function and diseases. Nat Rev Immunol 2009; 9:271–285.
Robertson AG, Shih J, Yau C, Gibb EA, Oba J, Mungall KL, et al. Integrative analysis identifies four molecular and clinical subsets in uveal melanoma. Cancer Cell 2017; 32:204–220.e15.
Ventii KH, Devi NS, Friedrich KL, Chernova TA, Tighiouart M, Van Meir EG, Wilkinson KD. BRCA1-associated protein-1 is a tumor suppressor that requires deubiquitinating activity and nuclear localization. Cancer Res 2008; 68:6953–6962.
Kalirai H, Dodson A, Faqir S, Damato BE, Coupland SE. Lack of BAP1 protein expression in uveal melanoma is associated with increased metastatic risk and has utility in routine prognostic testing. Br J Cancer 2014; 111:1373–1380.
Tabuenca Del Barrio L, Nova-Camacho LM, Zubicoa Enériz A, Martínez de Espronceda Ezquerro I, Córdoba Iturriagagoitia A, Borque Rodríguez-Maimón E, et al. Prognostic factor utility of BAP1 immunohistochemistry in uveal melanoma: a single center study in Spain. Cancers (Basel) 2021; 13:5347.
Field MG, Kuznetsov JN, Bussies PL, Cai LZ, Alawa KA, Decatur CL, et al. BAP1 loss is associated with DNA methylomic repatterning in highly aggressive class 2 uveal melanomas. Clin Cancer Res 2019; 25:5663–5673.
Figueiredo CR, Kalirai H, Sacco JJ, Azevedo RA, Duckworth A, Slupsky JR, et al. Loss of BAP1 expression is associated with an immunosuppressive microenvironment in uveal melanoma, with implications for immunotherapy development. J Pathol 2020; 250:420–439.
Shrestha R, Nabavi N, Lin YY, Mo F, Anderson S, Volik S, et al. BAP1 haploinsufficiency predicts a distinct immunogenic class of malignant peritoneal mesothelioma. Genome Med 2019; 11:8.
Karlsson J, Nilsson LM, Mitra S, Alsén S, Shelke GV, Sah VR, et al. Molecular profiling of driver events in metastatic uveal melanoma. Nat Commun 2020; 11:1894.
de Vos L, Carrillo Cano TM, Zarbl R, Klümper N, Ralser DJ, Franzen A, et al. CTLA4, PD-1, PD-L1, PD-L2, TIM-3, TIGIT, and LAG3 DNA methylation is associated with BAP1-aberrancy, transcriptional activity, and overall survival in uveal melanoma. J Immunother 2022; 45:324–334.
Durante MA, Rodriguez DA, Kurtenbach S, Kuznetsov JN, Sanchez MI, Decatur CL, et al. Single-cell analysis reveals new evolutionary complexity in uveal melanoma. Nat Commun 2020; 11:496.
Gevensleben H, Holmes EE, Goltz D, Dietrich J, Sailer V, Ellinger J, et al. PD-L1 promoter methylation is a prognostic biomarker for biochemical recurrence-free survival in prostate cancer patients following radical prostatectomy. Oncotarget 2016; 7:79943–79955.
Goltz D, Gevensleben H, Dietrich J, Dietrich D. PD-L1 (CD274) promoter methylation predicts survival in colorectal cancer patients. Oncoimmunology 2017; 6:e1257454.
Goltz D, Gevensleben H, Vogt TJ, Dietrich J, Golletz C, Bootz F, et al. CTLA4 methylation predicts response to anti-PD-1 and anti-CTLA-4 immunotherapy in melanoma patients. JCI Insight 2018; 3:12.
Fietz S, Zarbl R, Niebel D, Posch C, Brossart P, Gielen GH, et al. CTLA4 promoter methylation predicts response and progression-free survival in stage IV melanoma treated with anti-CTLA-4 immunotherapy (ipilimumab). Cancer Immunol Immunother 2021; 70:1781–1788.
Klümper N, Ralser DJ, Zarbl R, Schlack K, Schrader AJ, Rehlinghaus M, et al. CTLA4 promoter hypomethylation is a negative prognostic biomarker at initial diagnosis but predicts response and favorable outcome to anti-PD-1 based immunotherapy in clear cell renal cell carcinoma. J ImmunoTher Cancer 2021; 9:e002949.
Cancer Genome Atlas Network. Genomic classification of cutaneous melanoma. Cell 2015; 161:1681–1696.
Jones PA. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet 2012; 13:484–492.
Posner MR, Cavacini LA, Upton MP, Tillman KC, Gornstein ER, Norris CM. Surface membrane-expressed CD40 is present on tumor cells from squamous cell cancer of the head and neck in vitro and in vivo and regulates cell growth in tumor cell lines. Clin Cancer Res 1999; 5:2261–2270.
Zhang G-B, Dong QM, Hou JQ, Ge Y, Ju SG, Lu BF, Zhang XG. Characterization and application of three novel monoclonal antibodies against human 4-1BB: distinct epitopes of human 4-1BB on lung tumor cells and immune cells. Tissue Antigens 2007; 70:470–479.
Kim H, Kim Y, Bae S, Kong JM, Choi J, Jang M, et al. Direct interaction of CD40 on tumor cells with CD40L on T cells increases the proliferation of tumor cells by enhancing TGF-β production and Th17 differentiation. PLoS One 2015; 10:e0125742.
Starzer AM, Berghoff AS. New emerging targets in cancer immunotherapy: CD27 (TNFRSF7). ESMO Open 2020; 4(Suppl 3):e000629.
Chen P, Wang H, Zhao L, Guo H, Zhang L, Zhang W, et al. Immune checkpoints OX40 and OX40L in small-cell lung cancer: predict prognosis and modulate immune microenvironment. Front Oncol 2021; 11:713853.
Yan C, Saleh N, Yang J, Nebhan CA, Vilgelm AE, Reddy EP, et al. Novel induction of CD40 expression by tumor cells with RAS/RAF/PI3K pathway inhibition augments response to checkpoint blockade. Mol Cancer 2021; 20:85.
Gao G, Deng A, Liang S, Liu S, Fu X, Zhao X, Yu Z. Integration of bulk RNA sequencing and single-cell RNA sequencing to reveal uveal melanoma tumor heterogeneity and cells related to survival. Front Immunol 2022; 13:898925.
Pandiani C, Strub T, Nottet N, Cheli Y, Gambi G, Bille K, et al. Single-cell RNA sequencing reveals intratumoral heterogeneity in primary uveal melanomas and identifies HES6 as a driver of the metastatic disease. Cell Death Differ 2021; 28:1990–2000.
Watts TH. TNF/TNFR family members in costimulation of T cell responses. Annu Rev Immunol 2005; 23:23–68.
Elgueta R, Benson MJ, de Vries VC, Wasiuk A, Guo Y, Noelle RJ. Molecular mechanism and function of CD40/CD40L engagement in the immune system. Immunol Rev 2009; 229:152–172.
Cohen AD, Schaer DA, Liu C, Li Y, Hirschhorn-Cymmerman D, Kim SC, et al. Agonist anti-GITR monoclonal antibody induces melanoma tumor immunity in mice by altering regulatory T cell stability and intra-tumor accumulation. PLoS One 2010; 5:e10436.
Compte M, Harwood SL, Muñoz IG, Navarro R, Zonca M, Perez-Chacon G, et al. A tumor-targeted trimeric 4-1BB-agonistic antibody induces potent anti-tumor immunity without systemic toxicity. Nat Commun 2018; 9:4809.
Peng W, Williams LJ, Xu C, Melendez B, McKenzie JA, Chen Y, et al. Anti-OX40 antibody directly enhances the function of tumor-reactive CD8 + T cells and synergizes with PI3Kβ inhibition in PTEN loss melanoma. Clin Cancer Res 2019; 25:6406–6416.
Sandin LC, Orlova A, Gustafsson E, Ellmark P, Tolmachev V, Tötterman TH, Mangsbo SM. Locally delivered CD40 agonist antibody accumulates in secondary lymphoid organs and eradicates experimental disseminated bladder cancer. Cancer Immunol Res 2014; 2:80–90.
He L-Z, Prostak N, Thomas LJ, Vitale L, Weidlick J, Crocker A, et al. Agonist anti-human CD27 monoclonal antibody induces T cell activation and tumor immunity in human CD27-transgenic mice. J Immunol 2013; 191:4174–4183.
Fröhlich A, Loick S, Bawden EG, Fietz S, Dietrich J, Diekmann E, et al. Comprehensive analysis of tumor necrosis factor receptor TNFRSF9 (4-1BB) DNA methylation with regard to molecular and clinicopathological features, immune infiltrates, and response prediction to immunotherapy in melanoma. EBioMedicine 2020; 52:102647.
Johansson P, Aoude LG, Wadt K, Glasson WJ, Warrier SK, Hewitt AW, et al. Deep sequencing of uveal melanoma identifies a recurrent mutation in PLCB4. Oncotarget 2016; 7:4624–4631.
Lee N, Zakka LR, Mihm MC, Schatton T. Tumour-infiltrating lymphocytes in melanoma prognosis and cancer immunotherapy. Pathology (Phila) 2016; 48:177–187.
de la Cruz PO, Specht CS, McLean IW. Lymphocytic infiltration in uveal malignant melanoma. Cancer 1990; 65:112–115.
Maat W, Ly LV, Jordanova ES, Wolff-Rouendaal D. de, Schalij-Delfos NE, Jager MJ. Monosomy of chromosome 3 and an inflammatory phenotype occur together in uveal melanoma. Invest Ophthalmol Vis Sci 2008; 49:505–510.
García-Mulero S, Alonso MH, Del Carpio LP, Sanz-Pamplona R, Piulats JM. Additive role of immune system infiltration and angiogenesis in uveal melanoma progression. Int J Mol Sci 2021; 22:2669.
Hoefsmit EP, Rozeman EA, Van TM, Dimitriadis P, Krijgsman O, Conway JW, et al. Comprehensive analysis of cutaneous and uveal melanoma liver metastases. J ImmunoTher Cancer 2020; 8:e001501.
Taylor AW. Ocular immune privilege and transplantation. Front Immunol 2016; 7:37.
Chandran SS, Somerville RPT, Yang JC, Sherry RM, Klebanoff CA, Goff SL, et al. Treatment of metastatic uveal melanoma with adoptive transfer of tumour-infiltrating lymphocytes: a single-centre, two-stage, single-arm, phase 2 study. Lancet Oncol 2017; 18:792–802.