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
<b>Background/Objectives:</b> 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 op...
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MDPI AG
2024-03-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/13/6/1554 |
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| author | Maciej Kaczorowski Jerzy Lasota Krzysztof Dudek Bartosz Małkiewicz Markku Miettinen Agnieszka Hałoń |
| author_facet | Maciej Kaczorowski Jerzy Lasota Krzysztof Dudek Bartosz Małkiewicz Markku Miettinen Agnieszka Hałoń |
| author_sort | Maciej Kaczorowski |
| collection | DOAJ |
| description | <b>Background/Objectives:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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. |
| first_indexed | 2024-04-24T18:09:40Z |
| format | Article |
| id | doaj.art-dcff5e4d69df4184b532d2baff9883c4 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-04-24T18:09:40Z |
| publishDate | 2024-03-01 |
| publisher | MDPI AG |
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| series | Journal of Clinical Medicine |
| spelling | doaj.art-dcff5e4d69df4184b532d2baff9883c42024-03-27T13:47:41ZengMDPI AGJournal of Clinical Medicine2077-03832024-03-01136155410.3390/jcm13061554Expression of Immunotherapy Target PRAME in Cancer Correlates with Histone H3 Acetylation and Is Unrelated to Expression of Methylating (DMNT3A/3B) and Demethylating (TET1) EnzymesMaciej Kaczorowski0Jerzy Lasota1Krzysztof Dudek2Bartosz Małkiewicz3Markku Miettinen4Agnieszka Hałoń5Department of Clinical and Experimental Pathology, Wroclaw Medical University, 50-556 Wrocław, PolandLaboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, USAFaculty of Mechanical Engineering, Wroclaw University of Science and Technology, 50-370 Wrocław, PolandUniversity Center of Excellence in Urology, Department of Minimally Invasive and Robotic Urology, Wroclaw Medical University, 50-556 Wrocław, PolandLaboratory of Pathology, National Cancer Institute, Bethesda, MD 20892, USADepartment of Clinical and Experimental Pathology, Wroclaw Medical University, 50-556 Wrocław, Poland<b>Background/Objectives:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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. <b>Conclusions:</b> 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.https://www.mdpi.com/2077-0383/13/6/1554PRAMETET1DNMT3ADNMT3B5hmCH3ac |
| spellingShingle | Maciej Kaczorowski Jerzy Lasota Krzysztof Dudek Bartosz Małkiewicz Markku Miettinen Agnieszka Hałoń 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 Journal of Clinical Medicine PRAME TET1 DNMT3A DNMT3B 5hmC H3ac |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | PRAME TET1 DNMT3A DNMT3B 5hmC H3ac |
| url | https://www.mdpi.com/2077-0383/13/6/1554 |
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