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

Oncoimmunology
Mia Aaboe JørgensenMads Hald Andersen

Abstract

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.

References

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Feb 6, 2018·Oncoimmunology·Evelina MartinenaiteMads Hald Andersen

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Citations

Nov 7, 2019·Cancer Immunology, Immunotherapy : CII·Evelina MartinenaiteMads Hald Andersen
Oct 18, 2018·Frontiers in Immunology·Uffe KlausenMads Hald Andersen
Jul 11, 2018·Seminars in Immunopathology·Morten Orebo Holmström, Hans Carl Hasselbalch
Jul 2, 2020·Cells·Lukas M Braun, Robert Zeiser
Mar 7, 2021·International Journal of Molecular Sciences·Vincenzo NasilloTommaso Trenti
Sep 15, 2021·Cancer Immunology Research·Mia Aaboe JørgensenMads Hald Andersen

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Methods Mentioned

BETA
FACS

Software Mentioned

GraphPad
ImmunoSpot
Prism
CTL

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