Biomaterial Database

CTLA4 promoter methylation predicts response and progression-free survival in stage IV melanoma treated with anti-CTLA-4 immunotherapy (ipilimumab). 2021

Simon Fietz, and Romina Zarbl, and Dennis Niebel, and Christian Posch, and Peter Brossart, and Gerrit H Gielen, and Sebastian Strieth, and Torsten Pietsch, and Glen Kristiansen, and Friedrich Bootz, and Jennifer Landsberg, and Dimo Dietrich

Department of Dermatology and Allergy, University Hospital Bonn, Venusberg-Campus, Bonn, 53127, Germany.

Anti-CTLA-4-antibodies can induce long-lasting tumor remissions. However, only a few patients respond, necessitating the development of predictive companion biomarkers. Increasing evidence suggests a major role of epigenetics, including DNA methylation, in immunology and resistance to immune checkpoint blockade. Here, we tested CTLA4 promoter methylation and CTLA-4 protein expression as predictive biomarkers for response to anti-CTLA-4 immunotherapy. We identified retrospectively N = 30 stage IV melanoma patients treated with single-agent anti-CTLA-4 immunotherapy (ipilimumab). We used quantitative methylation-specific PCR and immunohistochemistry to quantify CTLA4 methylation and protein expression in pre-treatment samples. CTLA4 methylation was significantly higher in progressive as compared to responding tumors and significantly associated with progression-free survival. A subset of infiltrating lymphocytes and tumor cells highly expressed CTLA-4. However, CTLA-4 protein expression did not predict response to treatment. We conclude that CTLA4 methylation is a predictive biomarker for response to anti-CTLA-4 immunotherapy.

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008545	Melanoma	A malignant neoplasm derived from cells that are capable of forming melanin, which may occur in the skin of any part of the body, in the eye, or, rarely, in the mucous membranes of the genitalia, anus, oral cavity, or other sites. It occurs mostly in adults and may originate de novo or from a pigmented nevus or malignant lentigo. Melanomas frequently metastasize widely, and the regional lymph nodes, liver, lungs, and brain are likely to be involved. The incidence of malignant skin melanomas is rising rapidly in all parts of the world. (Stedman, 25th ed; from Rook et al., Textbook of Dermatology, 4th ed, p2445)	Malignant Melanoma,Malignant Melanomas,Melanoma, Malignant,Melanomas,Melanomas, Malignant
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D011379	Prognosis	A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.	Prognostic Factor,Prognostic Factors,Factor, Prognostic,Factors, Prognostic,Prognoses
D011401	Promoter Regions, Genetic	DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.	rRNA Promoter,Early Promoters, Genetic,Late Promoters, Genetic,Middle Promoters, Genetic,Promoter Regions,Promoter, Genetic,Promotor Regions,Promotor, Genetic,Pseudopromoter, Genetic,Early Promoter, Genetic,Genetic Late Promoter,Genetic Middle Promoters,Genetic Promoter,Genetic Promoter Region,Genetic Promoter Regions,Genetic Promoters,Genetic Promotor,Genetic Promotors,Genetic Pseudopromoter,Genetic Pseudopromoters,Late Promoter, Genetic,Middle Promoter, Genetic,Promoter Region,Promoter Region, Genetic,Promoter, Genetic Early,Promoter, rRNA,Promoters, Genetic,Promoters, Genetic Middle,Promoters, rRNA,Promotor Region,Promotors, Genetic,Pseudopromoters, Genetic,Region, Genetic Promoter,Region, Promoter,Region, Promotor,Regions, Genetic Promoter,Regions, Promoter,Regions, Promotor,rRNA Promoters
D005260	Female		Females
D005500	Follow-Up Studies	Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.	Followup Studies,Follow Up Studies,Follow-Up Study,Followup Study,Studies, Follow-Up,Studies, Followup,Study, Follow-Up,Study, Followup
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000074322	Antineoplastic Agents, Immunological	Antineoplastic agents containing immunological agents (e.g. MAbs). These pharmacologic preparations inhibit or prevent the proliferation of NEOPLASMS.	Antineoplastic MAbs,Antineoplastics, Monoclonal Antibodies,Antineoplastics, Monoclonal Antibody,MAbs, Antineoplastic,Monoclonal Antibodies, Antineoplastic,Antibodies Antineoplastics, Monoclonal,Antineoplastic Monoclonal Antibodies,Immunological Antineoplastic Agents,Monoclonal Antibodies Antineoplastics,Monoclonal Antibody Antineoplastics
D000074324	Ipilimumab	An anti-CTLA-4 ANTIGEN monoclonal antibody initially indicated for the treatment of certain types of metastatic MELANOMA. Its mode of actions may include blocking of CTLA-4 mediated inhibition of CYTOTOXIC T LYMPHOCYTES, allowing for more efficient destruction of target tumor cells.	Anti-CTLA-4 MAb Ipilimumab,MDX 010,MDX-010,MDX-CTLA-4,MDX010,Yervoy,Anti CTLA 4 MAb Ipilimumab,Ipilimumab, Anti-CTLA-4 MAb,MDX CTLA 4