Increase in circulating CD4CD25Foxp3 T cells in patients with Philadelphia-negative chronic myeloproliferative neoplasms during treatment with IFN-α

TY - JOUR

T1 - Increase in circulating CD4CD25Foxp3 T cells in patients with Philadelphia-negative chronic myeloproliferative neoplasms during treatment with IFN-α

AU - Riley, C.H.

AU - Morten Krogh, Jensen

AU - Brimnes, M.K.

AU - Straten, P.T.

AU - Svane, I.M.

AU - Hasselbalch, H.C.

AU - Bjerrum, O.W.

PY - 2011/8/25

Y1 - 2011/8/25

N2 - Recent reports have described complete or major molecular remission in patients with polycythemia vera after long-term treatment with the immunomodulatory agent IFN-α2. Accordingly, there are reasons to believe that the immune system is a key player in eradicating the JAK2 mutated clone in these patients. Foxp3+ regulatory T cells play a pivotal role in maintaining immune homeostasis and, importantly, preventing immune reactivity to self-antigens; however, their suppressive activity can compromise an effective antitumor immune response, and high frequencies of regulatory T cells in peripheral blood have been reported in both hematologic and solid cancers. We have analyzed the number, phenotype, and function of circulating CD4 +CD25+Foxp3+ T cells in patients with chronic myeloproliferative neoplasms. Surprisingly, we found a marked expansion of this subset of lymphocytes in patients treated with IFN-α2 (13.0%; 95% confidence interval [CI] 10.8% to 15.2%) compared with healthy donors (6.1%; 95% CI 4.9% to 7.2%), patients with untreated chronic myeloproliferative neoplasms (6.9%; 95% CI 5.8% to 7.4%), or patients treated with hydroxyurea (5.8%; 95% CI 4.3% to 7.4%; P < .0001).

AB - Recent reports have described complete or major molecular remission in patients with polycythemia vera after long-term treatment with the immunomodulatory agent IFN-α2. Accordingly, there are reasons to believe that the immune system is a key player in eradicating the JAK2 mutated clone in these patients. Foxp3+ regulatory T cells play a pivotal role in maintaining immune homeostasis and, importantly, preventing immune reactivity to self-antigens; however, their suppressive activity can compromise an effective antitumor immune response, and high frequencies of regulatory T cells in peripheral blood have been reported in both hematologic and solid cancers. We have analyzed the number, phenotype, and function of circulating CD4 +CD25+Foxp3+ T cells in patients with chronic myeloproliferative neoplasms. Surprisingly, we found a marked expansion of this subset of lymphocytes in patients treated with IFN-α2 (13.0%; 95% confidence interval [CI] 10.8% to 15.2%) compared with healthy donors (6.1%; 95% CI 4.9% to 7.2%), patients with untreated chronic myeloproliferative neoplasms (6.9%; 95% CI 5.8% to 7.4%), or patients treated with hydroxyurea (5.8%; 95% CI 4.3% to 7.4%; P < .0001).

UR - http://www.scopus.com/inward/record.url?scp=80052143261&partnerID=8YFLogxK

U2 - 10.1182/blood-2011-03-340992

DO - 10.1182/blood-2011-03-340992

M3 - Journal article

C2 - 21708889

AN - SCOPUS:80052143261

SN - 0006-4971

VL - 118

SP - 2170

EP - 2173

JO - Blood

JF - Blood

IS - 8

ER -