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01-02-2020 | Chronic Myeloproliferative Neoplasms | Focussed Research Review

Evidence of immune elimination, immuno-editing and immune escape in patients with hematological cancer

Authors: Morten Orebo Holmström, Sabrina Cordua, Vibe Skov, Lasse Kjær, Niels Pallisgaard, Christina Ellervik, Hans Carl Hasselbalch, Mads Hald Andersen

Published in: Cancer Immunology, Immunotherapy | Issue 2/2020

Abstract

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.

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Title: Evidence of immune elimination, immuno-editing and immune escape in patients with hematological cancer
Authors: Morten Orebo Holmström
Sabrina Cordua
Vibe Skov
Lasse Kjær
Niels Pallisgaard
Christina Ellervik
Hans Carl Hasselbalch
Mads Hald Andersen
Publication date: 01-02-2020
Publisher: Springer Berlin Heidelberg
Keywords: Chronic Myeloproliferative Neoplasms
Primary Myelofibrosis
Primary Myelofibrosis
Published in: Cancer Immunology, Immunotherapy / Issue 2/2020
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-019-02473-y

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