Electronic Resource
Apparent Lack of BRAFV600E Derived HLA Class I Presented Neoantigens Hampers Neoplastic Cell Targeting by CD8+ T Cells in Langerhans Cell Histiocytosis
| العنوان: | Apparent Lack of BRAFV600E Derived HLA Class I Presented Neoantigens Hampers Neoplastic Cell Targeting by CD8+ T Cells in Langerhans Cell Histiocytosis |
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| المؤلفون: | Kemps, Paul G., Zondag, Timo C., Steenwijk, Eline C., Andriessen, Quirine, Borst, Jelske, Vloemans, Sandra, Roelen, Dave L., Voortman, Lenard M., Verdijk, Robert M., van Noesel, Carel J.M., Cleven, Arjen H.G., Hawkins, Cynthia, Lang, Veronica, de Ru, Arnoud H., Janssen, George M.C., Haasnoot, Geert W., Franken, Kees L.M.C., van Eijk, Ronald, Solleveld-Westerink, Nienke, van Wezel, Tom, Egeler, R. Maarten, Beishuizen, Auke, van Laar, Jan A.M., Abla, Oussama, van den Bos, Cor, van Veelen, Peter A., van Halteren, Astrid G.S. |
| المصدر: | Kemps , P G , Zondag , T C , Steenwijk , E C , Andriessen , Q , Borst , J , Vloemans , S , Roelen , D L , Voortman , L M , Verdijk , R M , van Noesel , C J M , Cleven , A H G , Hawkins , C , Lang , V , de Ru , A H , Janssen , G M C , Haasnoot , G W , Franken , K L M C , van Eijk , R , Solleveld-Westerink , N , van Wezel , T , Egeler , R M , Beishuizen , A , van Laar , J A M , Abla , O , van den Bos , C , van Veelen , P A & van Halteren , A G S 2020 , ' Apparent Lack of BRAF V600E Derived HLA Class I Presented Neoantigens Hampers Neoplastic Cell Targeting by CD8 + T Cells in Langerhans Cell Histiocytosis ' , Frontiers in Immunology , vol. 10 , 3045 . |
| بيانات النشر: | 2020-01-10 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Langerhans Cell Histiocytosis (LCH) is a neoplastic disorder of hematopoietic origin characterized by inflammatory lesions containing clonal histiocytes (LCH-cells) intermixed with various immune cells, including T cells. In 50–60% of LCH-patients, the somatic BRAFV600E driver mutation, which is common in many cancers, is detected in these LCH-cells in an otherwise quiet genomic landscape. Non-synonymous mutations like BRAFV600E can be a source of neoantigens capable of eliciting effective antitumor CD8+ T cell responses. This requires neopeptides to be stably presented by Human Leukocyte Antigen (HLA) class I molecules and sufficient numbers of CD8+ T cells at tumor sites. Here, we demonstrate substantial heterogeneity in CD8+ T cell density in n = 101 LCH-lesions, with BRAFV600E mutated lesions displaying significantly lower CD8+ T cell:CD1a+ LCH-cell ratios (p = 0.01) than BRAF wildtype lesions. Because LCH-lesional CD8+ T cell density had no significant impact on event-free survival, we investigated whether the intracellularly expressed BRAFV600E protein is degraded into neopeptides that are naturally processed and presented by cell surface HLA class I molecules. Epitope prediction tools revealed a single HLA class I binding BRAFV600E derived neopeptide (KIGDFGLATEK), which indeed displayed strong to intermediate binding capacity to HLA-A*03:01 and HLA-A*11:01 in an in vitro peptide-HLA binding assay. Mass spectrometry-based targeted peptidomics was used to investigate the presence of this neopeptide in HLA class I presented peptides isolated from several BRAFV600E expressing cell lines with various HLA genotypes. While the HLA-A*02:01 binding BRAF wildtype peptide KIGDFGLATV was traced in peptides isolated from all five cell lines expressing this HLA subtype, KIGDFGLATEK was not detected in the H |
| مصطلحات الفهرس: | dk/atira/pure/keywords/researchprograms/AFL001000/EMCMM025403; name=EMC MM-02-54-03, dk/atira/pure/keywords/researchprograms/AFL001000/EMCMM027202; name=EMC MM-02-72-02, dk/atira/pure/keywords/researchprograms/AFL001000/EMCMM032401; name=EMC MM-03-24-01, dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being; name=SDG 3 - Good Health and Well-being, article |
| URL: | |
| الاتاحة: | Open access content. Open access content info:eu-repo/semantics/openAccess |
| ملاحظة: | application/pdf English |
| Other Numbers: | QGQ oai:pure.eur.nl:publications/322e2c1f-711d-42bc-bb6d-7a5f20deeec6 https://pure.eur.nl/en/publications/322e2c1f-711d-42bc-bb6d-7a5f20deeec6 https://doi.org/10.3389/fimmu.2019.03045 https://pure.eur.nl/ws/files/117200869/Apparent_Lack_of_BRAFV600E_Derived_HLA_Class_I_Presented_Neoantigens_Hampers_Neoplastic_Cell_Targeting_by_CD8_T_Cells_in_Langerhans_Cell_Histiocytosis.pdf 1313627466 |
| المصدر المساهم: | ERASMUS UNIVERSITEIT ROTTERDAM From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1313627466 |
| قاعدة البيانات: | OAIster |
| الوصف غير متاح. |