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B-cell frequencies and immunoregulatory phenotypes in myeloproliferative neoplasms: Influence of ruxolitinib, interferon-α2, or combination treatment.

Abstract

OBJECTIVE

Given a proposed role for PD-L1+ and IL-10-producing B-cell subsets in promoting certain cancers, we sought to characterize the frequency and phenotype of B cells in patients with chronic myeloproliferative neoplasms (MPNs) and the influence of ruxolitinib and interferon-α2 therapy.

METHODS

We analyzed B-cell frequencies and phenotype in patients with MPNs (n = 107), before and during treatment with ruxolitinib (n = 29), interferon-α2 (n = 21), or the two drugs in combination (COMBI; n = 42) and healthy donors (HDs; n = 52) using flow cytometry.

RESULTS

Myelofibrosis patients had lower lymphocyte counts and proportions of B cells than patients with essential thrombocythemia or polycythemia vera and HDs. The B-cell count correlated inversely with JAK2-V617F allele burden and spleen size and increased after ruxolitinib or COMBI treatment. The proportions of PD-L1+ B cells and PD-1+ B cells were significantly higher in patients with myelofibrosis or polycythemia vera than in HDs and decreased during ruxolitinib and COMBI treatment. The proportions of TNF-α+ and IL-6+ B cells were elevated in myelofibrosis patients. The proportion of IL-6+ B cells decreased, and the proportion of IL-10+ B cells increased during ruxolitinib treatment.

CONCLUSION

B-cell frequency and phenotype were altered in MPN patients. Ruxolitinib therapy had marked effects on both frequency and phenotype.

Authors+Show Affiliations

Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. Department of Hematology, Zealand University Hospital, Roskilde, Denmark.Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. Department of Hematology, Zealand University Hospital, Roskilde, Denmark.Department of Hematology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.Department of Hematology, Zealand University Hospital, Roskilde, Denmark. Department of Hematology, Center for Cancer Immune Therapy, Copenhagen University Hospital at Herlev, Herlev, Denmark.Department of Hematology, Center for Cancer Immune Therapy, Copenhagen University Hospital at Herlev, Herlev, Denmark.Department of Hematology, Center for Cancer Immune Therapy, Copenhagen University Hospital at Herlev, Herlev, Denmark.Department of Hematology, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.Department of Hematology, Zealand University Hospital, Roskilde, Denmark.Department of Hematology, Zealand University Hospital, Roskilde, Denmark.Department of Hematology, Zealand University Hospital, Roskilde, Denmark.Institute for Inflammation Research, Center for Rheumatology and Spine Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31297883

Citation

Sørensen, Anders Lindholm, et al. "B-cell Frequencies and Immunoregulatory Phenotypes in Myeloproliferative Neoplasms: Influence of Ruxolitinib, Interferon-α2, or Combination Treatment." European Journal of Haematology, 2019.
Sørensen AL, Bjørn ME, Riley CH, et al. B-cell frequencies and immunoregulatory phenotypes in myeloproliferative neoplasms: Influence of ruxolitinib, interferon-α2, or combination treatment. Eur J Haematol. 2019.
Sørensen, A. L., Bjørn, M. E., Riley, C. H., Holmstrøm, M., Andersen, M. H., Svane, I. M., ... Nielsen, C. H. (2019). B-cell frequencies and immunoregulatory phenotypes in myeloproliferative neoplasms: Influence of ruxolitinib, interferon-α2, or combination treatment. European Journal of Haematology, doi:10.1111/ejh.13292.
Sørensen AL, et al. B-cell Frequencies and Immunoregulatory Phenotypes in Myeloproliferative Neoplasms: Influence of Ruxolitinib, Interferon-α2, or Combination Treatment. Eur J Haematol. 2019 Jul 11; PubMed PMID: 31297883.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - B-cell frequencies and immunoregulatory phenotypes in myeloproliferative neoplasms: Influence of ruxolitinib, interferon-α2, or combination treatment. AU - Sørensen,Anders Lindholm, AU - Bjørn,Mads Emil, AU - Riley,Caroline H, AU - Holmstrøm,Morten, AU - Andersen,Mads Hald, AU - Svane,Inge Marie, AU - Mikkelsen,Stine Ulrik, AU - Skov,Vibe, AU - Kjaer,Lasse, AU - Hasselbalch,Hans C, AU - Nielsen,Claus H, Y1 - 2019/07/11/ PY - 2019/04/29/received PY - 2019/07/04/revised PY - 2019/07/05/accepted PY - 2019/7/13/pubmed PY - 2019/7/13/medline PY - 2019/7/13/entrez KW - Myeloproliferative neoplasms JF - European journal of haematology JO - Eur. J. Haematol. N2 - OBJECTIVE: Given a proposed role for PD-L1+ and IL-10-producing B-cell subsets in promoting certain cancers, we sought to characterize the frequency and phenotype of B cells in patients with chronic myeloproliferative neoplasms (MPNs) and the influence of ruxolitinib and interferon-α2 therapy. METHODS: We analyzed B-cell frequencies and phenotype in patients with MPNs (n = 107), before and during treatment with ruxolitinib (n = 29), interferon-α2 (n = 21), or the two drugs in combination (COMBI; n = 42) and healthy donors (HDs; n = 52) using flow cytometry. RESULTS: Myelofibrosis patients had lower lymphocyte counts and proportions of B cells than patients with essential thrombocythemia or polycythemia vera and HDs. The B-cell count correlated inversely with JAK2-V617F allele burden and spleen size and increased after ruxolitinib or COMBI treatment. The proportions of PD-L1+ B cells and PD-1+ B cells were significantly higher in patients with myelofibrosis or polycythemia vera than in HDs and decreased during ruxolitinib and COMBI treatment. The proportions of TNF-α+ and IL-6+ B cells were elevated in myelofibrosis patients. The proportion of IL-6+ B cells decreased, and the proportion of IL-10+ B cells increased during ruxolitinib treatment. CONCLUSION: B-cell frequency and phenotype were altered in MPN patients. Ruxolitinib therapy had marked effects on both frequency and phenotype. SN - 1600-0609 UR - https://www.unboundmedicine.com/medline/citation/31297883/B-cell_frequencies_and_immunoregulatory_phenotypes_in_myeloproliferative_neoplasms:_influence_of_ruxolitinib,_interferon-α2,_or_combination_treatment L2 - https://doi.org/10.1111/ejh.13292 DB - PRIME DP - Unbound Medicine ER -