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The Capital Region of Denmark - a part of Copenhagen University Hospital
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Evidence of immune elimination, immuno-editing and immune escape in patients with hematological cancer

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  1. Arginase-1-based vaccination against the tumor microenvironment: the identification of an optimal T-cell epitope

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  2. TAM-ing T cells in the tumor microenvironment: implications for TAM receptor targeting

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  3. Tumor-induced escape mechanisms and their association with resistance to checkpoint inhibitor therapy

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  4. Cancer immunotherapy in patients with brain metastases

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  5. NY-ESO-1- and survivin-specific T-cell responses in the peripheral blood from patients with glioma

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  1. Estimates of prediabetes and undiagnosed type 2 diabetes in Denmark: The end of an epidemic or a diagnostic artefact?

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  2. The Danish Rural Eye Study: prevalence of strabismus among 3785 Danish adults - a population-based cross-sectional study

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  3. Arginase-1-based vaccination against the tumor microenvironment: the identification of an optimal T-cell epitope

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  4. Terapeutisk cancervaccination mod hæmatologisk cancer

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There is mounting evidence that the immune system can spontaneously clear malignant lesions before they manifest as overt cancer, albeit this activity has been difficult to demonstrate in humans. The calreticulin (CALR) exon 9 mutations are driver mutations in patients with chronic myeloproliferative neoplasms (MPN), which are chronic blood cancers. The CALR mutations generate a neo-antigen that is recognized by patient T cells, and T cells isolated from a patient with a CALR-mutation can recognize and kill autologous CALR-mutant cells. Surprisingly, healthy individuals display frequent and strong T cell responses to the CALR neo-antigens too. Furthermore, healthy individuals display immune responses to all parts of the mutant CALR epitope, and the CALR neo-epitope specific responses are memory T cell responses. These data suggest that although healthy individuals might acquire a CALR mutation, the mutant cells can be eliminated by the immune system. Additionally, a small fraction of healthy individuals harbor a CALR exon 9 mutation. Four healthy individuals carrying CALR mutations underwent a full medical examination including a bone marrow biopsy after a median follow up of 6.2 years. None of these patients displayed any signs of CALR-mutant MPN. Additionally, all healthy individuals displayed strong CALR neo-epitope specific T cell responses suggesting that these healthy individuals retained their CALR-mutant cells in the editing stage for several years. Thus, we suggest that CALR-mutant MPN could be a disease model of cancer immuno-editing, as we have demonstrated that CALR-mutant MPN displays all three stages described in the theory of cancer immuno-editing.

Original languageEnglish
JournalCancer immunology, immunotherapy : CII
Volume69
Pages (from-to)315-24
ISSN0340-7004
DOIs
Publication statusPublished - Feb 2020

ID: 59227175