Identification of two HLA-A*0201 immunogenic epitopes of lactate dehydrogenase C (LDHC): potential novel targets for cancer immunotherapy
<p dir="ltr">Lactate dehydrogenase C (LDHC) is an archetypical cancer testis antigen with limited expression in adult tissues and re-expression in tumors. This restricted expression pattern together with the important role of LDHC in cancer metabolism renders LDHC a potential target...
محفوظ في:
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| مؤلفون آخرون: | , , , , |
| منشور في: |
2020
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| _version_ | 1864513555912458240 |
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| author | Remy Thomas (702843) |
| author2 | Hibah Shaath (5599658) Adviti Naik (673163) Salman M. Toor (8854751) Eyad Elkord (5396390) Julie Decock (44558) |
| author2_role | author author author author author |
| author_facet | Remy Thomas (702843) Hibah Shaath (5599658) Adviti Naik (673163) Salman M. Toor (8854751) Eyad Elkord (5396390) Julie Decock (44558) |
| author_role | author |
| dc.creator.none.fl_str_mv | Remy Thomas (702843) Hibah Shaath (5599658) Adviti Naik (673163) Salman M. Toor (8854751) Eyad Elkord (5396390) Julie Decock (44558) |
| dc.date.none.fl_str_mv | 2020-01-13T06:00:00Z |
| dc.identifier.none.fl_str_mv | 10.1007/s00262-020-02480-4 |
| dc.relation.none.fl_str_mv | https://figshare.com/articles/journal_contribution/Identification_of_two_HLA-A_0201_immunogenic_epitopes_of_lactate_dehydrogenase_C_LDHC_potential_novel_targets_for_cancer_immunotherapy/21596949 |
| 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 Clinical sciences Immunology Oncology and carcinogenesis LDHC Lactate dehydrogenase Cancer testis antigen Epitopes Adoptive T cell therapy Cancer immunotherapy |
| dc.title.none.fl_str_mv | Identification of two HLA-A*0201 immunogenic epitopes of lactate dehydrogenase C (LDHC): potential novel targets for cancer immunotherapy |
| dc.type.none.fl_str_mv | Text Journal contribution info:eu-repo/semantics/publishedVersion text contribution to journal |
| description | <p dir="ltr">Lactate dehydrogenase C (LDHC) is an archetypical cancer testis antigen with limited expression in adult tissues and re-expression in tumors. This restricted expression pattern together with the important role of LDHC in cancer metabolism renders LDHC a potential target for immunotherapy. This study is the first to investigate the immunogenicity of LDHC using T cells from healthy individuals. LDHC-specific T cell responses were induced by in vitro stimulation with synthetic peptides, or by priming with autologous peptide-pulsed dendritic cells. We evaluated T cell activation by IFN-γ ELISpot and determined cytolytic activity of HLA-A*0201-restricted T cells in breast cancer cell co-cultures. In vitro T cell stimulation induced IFN-γ secretion in response to numerous LDHC-derived peptides. Analysis of HLA-A*0201 responses revealed a significant T cell activation after stimulation with peptide pools 2 (PP2) and 8 (PP8). The PP2- and PP8-specific T cells displayed cytolytic activity against breast cancer cells with endogenous LDHC expression within a HLA-A*0201 context. We identified peptides LDHC<sup>41−55</sup> and LDHC<sup>288−303</sup> from PP2 and PP8 to elicit a functional cellular immune response. More specifically, we found an increase in IFN-γ secretion by CD8 + T cells and cancer-cell-killing of HLA-A*0201/LDHC positive breast cancer cells by LDHC<sup>41−55</sup>- and LDHC<sup>288−303</sup>-induced T cells, albeit with a possible antigen recognition threshold. The majority of induced T cells displayed an effector memory phenotype. To conclude, our findings support the rationale to assess LDHC as a targetable cancer testis antigen for immunotherapy, and in particular the HLA-A*0201 restricted LDHC<sup>41–5</sup>5 and LDHC288–303 peptides within LDHC.</p><h2>Other Information</h2><p dir="ltr">Published in: Cancer Immunology, Immunotherapy<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1007/s00262-020-02480-4" target="_blank">http://dx.doi.org/10.1007/s00262-020-02480-4</a></p> |
| eu_rights_str_mv | openAccess |
| id | Manara2_874a02a43cd8925f66489a393ae20a09 |
| identifier_str_mv | 10.1007/s00262-020-02480-4 |
| network_acronym_str | Manara2 |
| network_name_str | Manara2 |
| oai_identifier_str | oai:figshare.com:article/21596949 |
| publishDate | 2020 |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | CC BY 4.0 |
| spelling | Identification of two HLA-A*0201 immunogenic epitopes of lactate dehydrogenase C (LDHC): potential novel targets for cancer immunotherapyRemy Thomas (702843)Hibah Shaath (5599658)Adviti Naik (673163)Salman M. Toor (8854751)Eyad Elkord (5396390)Julie Decock (44558)Biomedical and clinical sciencesClinical sciencesImmunologyOncology and carcinogenesisLDHCLactate dehydrogenaseCancer testis antigenEpitopesAdoptive T cell therapyCancer immunotherapy<p dir="ltr">Lactate dehydrogenase C (LDHC) is an archetypical cancer testis antigen with limited expression in adult tissues and re-expression in tumors. This restricted expression pattern together with the important role of LDHC in cancer metabolism renders LDHC a potential target for immunotherapy. This study is the first to investigate the immunogenicity of LDHC using T cells from healthy individuals. LDHC-specific T cell responses were induced by in vitro stimulation with synthetic peptides, or by priming with autologous peptide-pulsed dendritic cells. We evaluated T cell activation by IFN-γ ELISpot and determined cytolytic activity of HLA-A*0201-restricted T cells in breast cancer cell co-cultures. In vitro T cell stimulation induced IFN-γ secretion in response to numerous LDHC-derived peptides. Analysis of HLA-A*0201 responses revealed a significant T cell activation after stimulation with peptide pools 2 (PP2) and 8 (PP8). The PP2- and PP8-specific T cells displayed cytolytic activity against breast cancer cells with endogenous LDHC expression within a HLA-A*0201 context. We identified peptides LDHC<sup>41−55</sup> and LDHC<sup>288−303</sup> from PP2 and PP8 to elicit a functional cellular immune response. More specifically, we found an increase in IFN-γ secretion by CD8 + T cells and cancer-cell-killing of HLA-A*0201/LDHC positive breast cancer cells by LDHC<sup>41−55</sup>- and LDHC<sup>288−303</sup>-induced T cells, albeit with a possible antigen recognition threshold. The majority of induced T cells displayed an effector memory phenotype. To conclude, our findings support the rationale to assess LDHC as a targetable cancer testis antigen for immunotherapy, and in particular the HLA-A*0201 restricted LDHC<sup>41–5</sup>5 and LDHC288–303 peptides within LDHC.</p><h2>Other Information</h2><p dir="ltr">Published in: Cancer Immunology, Immunotherapy<br>License: <a href="https://creativecommons.org/licenses/by/4.0" target="_blank">https://creativecommons.org/licenses/by/4.0</a><br>See article on publisher's website: <a href="http://dx.doi.org/10.1007/s00262-020-02480-4" target="_blank">http://dx.doi.org/10.1007/s00262-020-02480-4</a></p>2020-01-13T06:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.1007/s00262-020-02480-4https://figshare.com/articles/journal_contribution/Identification_of_two_HLA-A_0201_immunogenic_epitopes_of_lactate_dehydrogenase_C_LDHC_potential_novel_targets_for_cancer_immunotherapy/21596949CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/215969492020-01-13T06:00:00Z |
| spellingShingle | Identification of two HLA-A*0201 immunogenic epitopes of lactate dehydrogenase C (LDHC): potential novel targets for cancer immunotherapy Remy Thomas (702843) Biomedical and clinical sciences Clinical sciences Immunology Oncology and carcinogenesis LDHC Lactate dehydrogenase Cancer testis antigen Epitopes Adoptive T cell therapy Cancer immunotherapy |
| status_str | publishedVersion |
| title | Identification of two HLA-A*0201 immunogenic epitopes of lactate dehydrogenase C (LDHC): potential novel targets for cancer immunotherapy |
| title_full | Identification of two HLA-A*0201 immunogenic epitopes of lactate dehydrogenase C (LDHC): potential novel targets for cancer immunotherapy |
| title_fullStr | Identification of two HLA-A*0201 immunogenic epitopes of lactate dehydrogenase C (LDHC): potential novel targets for cancer immunotherapy |
| title_full_unstemmed | Identification of two HLA-A*0201 immunogenic epitopes of lactate dehydrogenase C (LDHC): potential novel targets for cancer immunotherapy |
| title_short | Identification of two HLA-A*0201 immunogenic epitopes of lactate dehydrogenase C (LDHC): potential novel targets for cancer immunotherapy |
| title_sort | Identification of two HLA-A*0201 immunogenic epitopes of lactate dehydrogenase C (LDHC): potential novel targets for cancer immunotherapy |
| topic | Biomedical and clinical sciences Clinical sciences Immunology Oncology and carcinogenesis LDHC Lactate dehydrogenase Cancer testis antigen Epitopes Adoptive T cell therapy Cancer immunotherapy |