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Updated: Aug 15, 2026
A Melanoma Patient-Derived Xenograft Model
Published on: May 20, 2019
Phenotypic and functional changes of human melanoma xenografts induced by DNA hypomethylation: immunotherapeutic
Sandra Coral1, Luca Sigalotti, Francesca Colizzi
1Department of Medical Oncology, Cancer Bioimmunotherapy Unit, Centro di Riferimento Oncologico, Istituto di Ricovero e Cura a Carattere Scientifico, Aviano, Italy.
Abstract:
Emerging in vitro evidence points to an immunomodulatory activity of DNA hypomethylating drugs in human malignancies. We investigated the potential of 5-aza-2'-deoxycytidine (5-AZA-CdR) to modulate the expression of cancer testis antigens (CTA) and of HLA class I antigens by melanoma xenografts, and the resulting modifications in immunogenicity of neoplastic cells. Three primary cultures of melanoma cells, selected for immune phenotype and growth rate, were grafted into BALB/c nu/nu mice that were injected intraperitoneally with different dose- and time-schedules of 5-AZA-CdR. Molecular analyses demonstrated a de novo long-lasting expression of the CTA MAGE-1, -2, -3, -4, -10, GAGE 1-6, NY-ESO-1, and the upregulation of MAGE-1, MAGE-3, and NY-ESO-1 levels in melanoma xenografts from 5-AZA-CdR-treated mice. Serological and biochemical analyses identified a de novo expression of NY-ESO-1 protein and a concomitant and persistent upregulation of HLA class I antigens and of HLA-A1 and -A2 alleles. Immunization of BALB/c mice with 5-AZA-CdR-treated melanoma cells generated high titer circulating anti-NY-ESO-1 antibodies. Altogether, the data obtained identify an immunomodulatory activity of 5-AZA-CdR in vivo and strongly suggest for its clinical use to design novel strategies of CTA-based chemo-immunotherapy for melanoma patients.
Insights
5-aza-2'-deoxycytidine (5-AZA-CdR) therapy in melanoma xenografts induced expression of cancer testis antigens and HLA class I antigens. This suggests 5-AZA-CdR could be a valuable tool in chemo-immunotherapy for melanoma.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- DNA hypomethylating drugs show promise for modulating immune responses in cancers.
- Cancer testis antigens (CTA) and HLA class I antigens are critical in tumor immune evasion and recognition.
Purpose of the Study:
- To investigate the in vivo immunomodulatory effects of 5-aza-2 -deoxycytidine (5-AZA-CdR) on melanoma xenografts.
- To assess the impact of 5-AZA-CdR on CTA and HLA class I antigen expression and melanoma cell immunogenicity.
Main Methods:
- Melanoma xenografts in BALB/c nu/nu mice were treated with varying doses and schedules of 5-AZA-CdR.
- Molecular analyses (gene expression), serological assays, and biochemical analyses were performed.
- Immunization studies were conducted using treated melanoma cells.
Main Results:
- 5-AZA-CdR treatment led to de novo and sustained expression of multiple CTA (MAGE, GAGE, NY-ESO-1) and upregulation of specific CTA.
- A persistent upregulation of HLA class I antigens, including HLA-A1 and -A2 alleles, was observed.
- Immunization with 5-AZA-CdR-treated cells generated high-titer anti-NY-ESO-1 antibodies.
Conclusions:
- 5-AZA-CdR demonstrates significant in vivo immunomodulatory activity in melanoma xenografts.
- The drug enhances melanoma cell immunogenicity by modulating CTA and HLA class I expression.
- These findings support the clinical application of 5-AZA-CdR in CTA-based chemo-immunotherapy for melanoma.
