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Expression of Immunotherapy Target PRAME in Cancer Correlates with Histone H3 Acetylation and Is Unrelated to Expression of Methylating (DMNT3A/3B) and Demethylating (TET1) Enzymes.
Kaczorowski, Maciej; Lasota, Jerzy; Dudek, Krzysztof; Malkiewicz, Bartosz; Miettinen, Markku; Halon, Agnieszka.
Afiliação
  • Kaczorowski M; Department of Clinical and Experimental Pathology, Wroclaw Medical University, 50-556 Wroclaw, Poland.
  • Lasota J; Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, USA.
  • Dudek K; Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, USA.
  • Malkiewicz B; Faculty of Mechanical Engineering, Wroclaw University of Science and Technology, 50-370 Wroclaw, Poland.
  • Miettinen M; University Center of Excellence in Urology, Department of Minimally Invasive and Robotic Urology, Wroclaw Medical University, 50-556 Wroclaw, Poland.
  • Halon A; Laboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, USA.
J Clin Med ; 13(6)2024 Mar 08.
Article em En | MEDLINE | ID: mdl-38541782
ABSTRACT
Background/

Objectives:

Preferentially expressed antigen in melanoma (PRAME), a member of the cancer testis antigen family, is a promising target for cancer immunotherapy. Understanding the epigenetic mechanisms involved in the regulation of PRAME expression might be crucial for optimizing anti-PRAME treatments.

Methods:

Three malignancies of different lineages (sinonasal melanoma, testicular seminoma, and synovial sarcoma), in which immunohistochemical (IHC) reactivity for PRAME is a common yet variable feature, were studied. The expression of PRAME, ten-eleven translocation demethylase 1 (TET1), and DNA methyltransferase (DNMT) 3A and 3B were evaluated using immunohistochemistry. Moreover, the expression of two epigenetic marks, 5-hydroxymethylcytosine (5hmC) and histone 3 acetylation (H3ac), was tested.

Results:

All PRAME-positive tumors expressed medium-to-high levels of H3ac but differed considerably with respect to other markers. In seminomas, PRAME expression correlated with TET1, but in melanomas and synovial sarcomas, it correlated with both DNMTs and DNMT3A, respectively.

Conclusions:

PRAME expression was not determined by a balance between the global expression of DNA methylating/demethylating enzymes. However, histone acetylation may be one of the epigenetic mechanisms involved in PRAME regulation. Thus, the therapeutic combination of histone deacetylase inhibitors and PRAME immunotherapy merits further investigation.
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Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article