High frequencies of circulating memory T cells specific for calreticulin exon 9 mutations in healthy individuals
| العنوان: | High frequencies of circulating memory T cells specific for calreticulin exon 9 mutations in healthy individuals |
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| المؤلفون: | Niels Pallisgaard, Caroline Hasselbalch Riley, Hans Carl Hasselbalch, Evelina Martinenaite, Lasse Kjær, Inge Marie Svane, Christina Ellervik, Mads Hald Andersen, Shamaila Munir Ahmad, Uffe Klausen, Simone Kloch Bendtsen, Vibe Skov, Morten Orebo Holmström |
| المصدر: | Blood Cancer Journal, Vol 9, Iss 2, Pp 1-14 (2019) Holmström, M O, Ahmad, S M, Klausen, U, Bendtsen, S K, Martinenaite, E, Riley, C H, Svane, I M, Kjær, L, Skov, V, Ellervik, C, Pallisgaard, N, Hasselbalch, H C & Andersen, M H 2019, ' High frequencies of circulating memory T cells specific for calreticulin exon 9 mutations in healthy individuals ', Blood Cancer Journal, vol. 9, no. 2, 8 . https://doi.org/10.1038/s41408-018-0166-4 |
| بيانات النشر: | Nature Publishing Group, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Adult, Adolescent, T-Lymphocytes, Mutant, Epitopes, T-Lymphocyte, T-Cell Antigen Receptor Specificity, medicine.disease_cause, lcsh:RC254-282, Epitope, Young Adult, 03 medical and health sciences, Exon, 0302 clinical medicine, Immune system, Immunity, medicine, Humans, Lymphocyte Count, Mutation, biology, Age Factors, Exons, Hematology, Janus Kinase 2, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Healthy Volunteers, Oncology, 030220 oncology & carcinogenesis, Immunology, biology.protein, CALR Exon 9 Mutation, Calreticulin, Immunologic Memory, 030215 immunology |
| الوصف: | Mutations in exon 9 of the calreticulin gene (CALR) frequently occur in patients with chronic myeloproliferative neoplasms (MPN). Patients exhibit spontaneous cellular immune responses to epitopes derived from the mutant CALR C-terminus, and CALR-mutant-specific T cells recognize autologous CALR-mutant malignant cells. This study investigated whether CALR-mutant-specific T cells occur naturally in CALRwt MPN-patients and in healthy individuals. Specific immune responses against epitopes in the mutant CALR peptide sequence were detected in both CALRwt MPN-patients and in healthy individuals. Healthy donors displayed more frequent and stronger CALR-mutant specific T-cell responses compared to the responses identified in CALR-mutant MPN-patients. Several T-cell responses were identified in healthy donors directly ex vivo. Importantly, by running functional analyses on live-sorted immune cells from healthy donors, we showed that circulating CALR-mutant-specific immune cells are T-memory cells. These findings suggest, that healthy individuals acquire a CALR exon 9 mutation, but the immune system reacts and clears the mutant cells, and during this reaction generates CALR-mutant specific T-memory cells. We believe that these findings provide the evidence for tumor immune surveillance in MPN. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2044-5385 |
| DOI: | 10.1038/s41408-018-0166-4 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::be317249e0c326b9d5d46c9c2ed10b85 http://link.springer.com/article/10.1038/s41408-018-0166-4 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....be317249e0c326b9d5d46c9c2ed10b85 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20445385 |
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| DOI: | 10.1038/s41408-018-0166-4 |