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

TY - JOUR

T1 - Spontaneous T-cell responses against Arginase-1 in the chronic myeloproliferative neoplasms relative to disease stage and type of driver mutation

AU - Jørgensen, Mia Aaboe

AU - Holmström, Morten Orebo

AU - Martinenaite, Evelina

AU - Riley, Caroline Hasselbalch

AU - Hasselbalch, Hans Carl

AU - Andersen, Mads Hald

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Arginase-1

KW - immune responses

KW - MPN

KW - therapeutic peptide vaccine

U2 - 10.1080/2162402x.2018.1468957

DO - 10.1080/2162402x.2018.1468957

M3 - Journal article

C2 - 30228936

AN - SCOPUS:85050563653

SN - 2162-4011

VL - 7

JO - OncoImmunology

JF - OncoImmunology

IS - 9

M1 - e1468957

ER -