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

Mia Aaboe Jørgensen, Morten Orebo Holmström, Evelina Martinenaite, Caroline Hasselbalch Riley, Hans Carl Hasselbalch, Mads Hald Andersen

Publikation: Bidrag til tidsskriftArtikelForskningpeer review

Abstrakt

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.

OriginalsprogEngelsk
Artikelnummere1468957
TidsskriftOncoImmunology
Vol/bind7
Udgave nummer9
DOI
StatusUdgivet - 2 sep. 2018

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