Spontaneous T-cell responses against Arginase-1 in the chronic myeloproliferative neoplasms relative to disease stage and type of driver mutation

Compelling evidence supports the existence of a profound immune dysregulation in patients with chronic myeloproliferative neoplasms (MPN). Increased Arginase-1 expression has been described in MPN patients and in solid cancers. This increase contributes to an immunosuppressive tumor microenvironment...

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Bibliographic Details
Published in:Oncoimmunology 2018-09, Vol.7 (9), p.e1468957-e1468957
Main Authors: Jørgensen, Mia Aaboe, Holmström, Morten Orebo, Martinenaite, Evelina, Riley, Caroline Hasselbalch, Hasselbalch, Hans Carl, Andersen, Mads Hald
Format: Article
Language:English
Subjects:
Arginase-1
immune responses
MPN
Original Research
therapeutic peptide vaccine
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Summary:Compelling evidence supports the existence of a profound immune dysregulation in patients with chronic myeloproliferative neoplasms (MPN). Increased Arginase-1 expression has been described in MPN patients and in solid cancers. This increase contributes to an immunosuppressive tumor microenvironment in MPN patients because of L-arginine depletion by Arginase-1-expressing regulatory cells and cancer cells, which subsequently limits the activation of circulating effector cells. In the present study, we demonstrate that Arginase-1-derived peptides are recognized by T cells among peripheral mononuclear blood cells from MPN patients. We characterized the Arginase-1-specific T cells as being CD4 + and found that the magnitude of response to the Arginase-1 peptides depends on disease stage. Activation of Arginase-1-specific T cells by vaccination could be an attractive novel immunotherapeutic approach to targeting malignant and suppressive cells in MPN patients in combination with other immunotherapeutics.
ISSN:2162-4011
2162-402X
2162-402X
DOI:10.1080/2162402X.2018.1468957