Spontaneous T-cell responses against Arginase-1 in the chronic myeloproliferative neoplasms relative to disease stage and type of driver mutation
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Spontaneous T-cell responses against Arginase-1 in the chronic myeloproliferative neoplasms relative to disease stage and type of driver mutation. / Jørgensen, Mia Aaboe; Holmström, Morten Orebo; Martinenaite, Evelina; Riley, Caroline Hasselbalch; Hasselbalch, Hans Carl; Andersen, Mads Hald.
I: OncoImmunology, Bind 7, Nr. 9, e1468957, 2018.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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
VL - 7
JO - OncoImmunology
JF - OncoImmunology
SN - 2162-4011
IS - 9
M1 - e1468957
ER -
ID: 208875526