Cancer testis antigen PRAME: An anti‐cancer target with immunomodulatory potential
<p dir="ltr">PReferentially expressed Antigen in Melanoma (PRAME) is a cancer testis antigen with restricted expression in somatic tissues and re-expression in poor prognostic solid tumours. PRAME has been extensively investigated as a target for immunotherapy, however, its role in m...
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2021
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| _version_ | 1864513539597664256 |
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| author | Adviti Naik (673163) |
| author2 | Remy Thomas (702843) Ghaneya Al‐Khadairi (14779417) Rim Bacha (14779420) Wouter Hendrickx (44559) Julie Decock (44558) |
| author2_role | author author author author author |
| author_facet | Adviti Naik (673163) Remy Thomas (702843) Ghaneya Al‐Khadairi (14779417) Rim Bacha (14779420) Wouter Hendrickx (44559) Julie Decock (44558) |
| author_role | author |
| dc.creator.none.fl_str_mv | Adviti Naik (673163) Remy Thomas (702843) Ghaneya Al‐Khadairi (14779417) Rim Bacha (14779420) Wouter Hendrickx (44559) Julie Decock (44558) |
| dc.date.none.fl_str_mv | 2021-10-06T21:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1111/jcmm.16967 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Cancer_testis_antigen_PRAME_An_anti_cancer_target_with_immunomodulatory_potential/22258555 |
| dc.rights.none.fl_str_mv | CC BY 4.0 info:eu-repo/semantics/openAccess |
| dc.subject.none.fl_str_mv | Biomedical and clinical sciences Oncology and carcinogenesis Cell Biology Molecular Medicine |
| dc.title.none.fl_str_mv | Cancer testis antigen PRAME: An anti‐cancer target with immunomodulatory potential |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">PReferentially expressed Antigen in Melanoma (PRAME) is a cancer testis antigen with restricted expression in somatic tissues and re-expression in poor prognostic solid tumours. PRAME has been extensively investigated as a target for immunotherapy, however, its role in modulating the anti-tumour immune response remains largely unknown. Here, we show that PRAME tumour expression is associated with worse survival in the TCGA breast cancer cohort, particularly in immune-unfavourable tumours. Using direct and indirect co-culture models, we found that PRAME overexpressing MDA-MB-468 breast cancer cells inhibit T cell activation and cytolytic potential, which could be partly restored by silencing of <i>PRAME</i>. Furthermore, silencing of <i>PRAME</i> reduced expression of several immune checkpoints and their ligands, including PD-1, LAG3, PD-L1, CD86, Gal-9 and VISTA. Interestingly, silencing of <i>PRAME</i> induced cancer cell killing to levels similar to anti-PD-L1 atezolizumab treatment. Comprehensive analysis of soluble inflammatory mediators and cancer cell expression of immune-related genes showed that PRAME tumour expression can suppress the expression and secretion of multiple pro-inflammatory cytokines, and mediators of T cell activation, differentiation and cytolysis. Together, our data indicate that targeting of PRAME offers a potential, novel dual therapeutic approach to specifically target tumour cells and regulate immune activation in the tumour microenvironment.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Cellular and Molecular Medicine<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1111/jcmm.16967" target="_blank">http://dx.doi.org/10.1111/jcmm.16967</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_b3f8e2c6348f15c733c9dcf5f2515c7f |
| identifier_str_mv | 10.1111/jcmm.16967 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/22258555 |
| publishDate | 2021 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Cancer testis antigen PRAME: An anti‐cancer target with immunomodulatory potentialAdviti Naik (673163)Remy Thomas (702843)Ghaneya Al‐Khadairi (14779417)Rim Bacha (14779420)Wouter Hendrickx (44559)Julie Decock (44558)Biomedical and clinical sciencesOncology and carcinogenesisCell BiologyMolecular Medicine<p dir="ltr">PReferentially expressed Antigen in Melanoma (PRAME) is a cancer testis antigen with restricted expression in somatic tissues and re-expression in poor prognostic solid tumours. PRAME has been extensively investigated as a target for immunotherapy, however, its role in modulating the anti-tumour immune response remains largely unknown. Here, we show that PRAME tumour expression is associated with worse survival in the TCGA breast cancer cohort, particularly in immune-unfavourable tumours. Using direct and indirect co-culture models, we found that PRAME overexpressing MDA-MB-468 breast cancer cells inhibit T cell activation and cytolytic potential, which could be partly restored by silencing of <i>PRAME</i>. Furthermore, silencing of <i>PRAME</i> reduced expression of several immune checkpoints and their ligands, including PD-1, LAG3, PD-L1, CD86, Gal-9 and VISTA. Interestingly, silencing of <i>PRAME</i> induced cancer cell killing to levels similar to anti-PD-L1 atezolizumab treatment. Comprehensive analysis of soluble inflammatory mediators and cancer cell expression of immune-related genes showed that PRAME tumour expression can suppress the expression and secretion of multiple pro-inflammatory cytokines, and mediators of T cell activation, differentiation and cytolysis. Together, our data indicate that targeting of PRAME offers a potential, novel dual therapeutic approach to specifically target tumour cells and regulate immune activation in the tumour microenvironment.</p><h2>Other Information</h2><p dir="ltr">Published in: Journal of Cellular and Molecular Medicine<br>License: <a href="http://creativecommons.org/licenses/by/4.0/" target="_blank">http://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1111/jcmm.16967" target="_blank">http://dx.doi.org/10.1111/jcmm.16967</a></p>2021-10-06T21:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1111/jcmm.16967https://figshare.com/articles/journal_contribution/Cancer_testis_antigen_PRAME_An_anti_cancer_target_with_immunomodulatory_potential/22258555CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/222585552021-10-06T21:00:00Z |
| spellingShingle | Cancer testis antigen PRAME: An anti‐cancer target with immunomodulatory potential Adviti Naik (673163) Biomedical and clinical sciences Oncology and carcinogenesis Cell Biology Molecular Medicine |
| status_str | publishedVersion |
| title | Cancer testis antigen PRAME: An anti‐cancer target with immunomodulatory potential |
| title_full | Cancer testis antigen PRAME: An anti‐cancer target with immunomodulatory potential |
| title_fullStr | Cancer testis antigen PRAME: An anti‐cancer target with immunomodulatory potential |
| title_full_unstemmed | Cancer testis antigen PRAME: An anti‐cancer target with immunomodulatory potential |
| title_short | Cancer testis antigen PRAME: An anti‐cancer target with immunomodulatory potential |
| title_sort | Cancer testis antigen PRAME: An anti‐cancer target with immunomodulatory potential |
| topic | Biomedical and clinical sciences Oncology and carcinogenesis Cell Biology Molecular Medicine |