Patients With Myeloproliferative Neoplasms Harbor High Frequencies of CD8 T Cell-Platelet Aggregates Associated With T Cell Suppression
Por:
Simoes, AM, Holmstrom, MO, Aehnlich, P, Rahbech, A, Radziwon-Balicka, A, Zamora, C, Klausen, TW, Skov, V, Kjaer, L, Ellervik, C, El Fassi, D, Vidal, S, Hasselbalch, HC, Andersen, MH, Straten, PT
Publicada:
6 may 2022
Resumen:
Myeloproliferative neoplasms (MPN) are chronic cancers of the hematopoietic stem cells in the bone marrow, and patients often harbor elevated numbers of circulating platelets (PLT). We investigated the frequencies of circulating PLT-lymphocyte aggregates in MPN patients and the effect of PLT-binding on CD8 T cell function. The phenotype of these aggregates was evaluated in 50 MPN patients and 24 controls, using flow cytometry. In vitro studies compared the proliferation, cytokine release, and cytoxicity of PLT-bound and PLT-free CD8 T cells. Frequencies of PLT-CD8 T cell aggregates, were significantly elevated in MPN patients. Advanced disease stage and CALR mutation associated with the highest aggregate frequencies with a predominance of PLT-binding to antigen-experienced CD8 T cells. PLT-bound CD8 T cells showed reduction in proliferation and cytotoxic capacity. Our data suggest that CD8 T cell responses are jeopardized in MPN patients. JAK2 and CALR exon 9 mutations - the two predominant driver mutations in MPN - are targets for natural T cell responses in MPN patients. Moreover, MPN patients have more infections compared to background. Thus, PLT binding to antigen experienced CD8 T cells could play a role in the inadequacy of the immune system to control MPN disease progression and prevent recurrent infections.
Filiaciones:
Simoes, AM:
Herlev Univ Hosp, Natl Ctr Canc Immune Therapy CCIT DK, Dept Oncol, Herlev, Denmark
Holmstrom, MO:
Herlev Univ Hosp, Natl Ctr Canc Immune Therapy CCIT DK, Dept Oncol, Herlev, Denmark
Aehnlich, P:
Herlev Univ Hosp, Natl Ctr Canc Immune Therapy CCIT DK, Dept Oncol, Herlev, Denmark
Rahbech, A:
Herlev Univ Hosp, Natl Ctr Canc Immune Therapy CCIT DK, Dept Oncol, Herlev, Denmark
Radziwon-Balicka, A:
Herlev Univ Hosp, Natl Ctr Canc Immune Therapy CCIT DK, Dept Oncol, Herlev, Denmark
Zamora, C:
Hosp Sant Creu & St Pau, IIB Sant Pau Inst Rec, Barcelona, Spain
Klausen, TW:
Herlev Univ Hosp, Natl Ctr Canc Immune Therapy CCIT DK, Dept Oncol, Herlev, Denmark
Skov, V:
Zealand Univ Hosp, Dept Hematol, Roskilde, Denmark
Kjaer, L:
Zealand Univ Hosp, Dept Hematol, Roskilde, Denmark
Ellervik, C:
Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark
Boston Childrens Hosp, Harvard Med Sch, Dept Lab Med, Boston, MA USA
Dept Data & Innovat Support, Soro, Region Zealand, Denmark
El Fassi, D:
Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark
Univ Hosp, Dept Hematol, Rigshosp, Copenhagen, Denmark
Vidal, S:
Hosp Sant Creu & St Pau, IIB Sant Pau Inst Rec, Barcelona, Spain
Hasselbalch, HC:
Zealand Univ Hosp, Dept Hematol, Roskilde, Denmark
Andersen, MH:
Herlev Univ Hosp, Natl Ctr Canc Immune Therapy CCIT DK, Dept Oncol, Herlev, Denmark
Univ Copenhagen, Fac Hlth & Med Sci, Dept Immunol & Microbiol, Copenhagen, Denmark
Straten, PT:
Herlev Univ Hosp, Natl Ctr Canc Immune Therapy CCIT DK, Dept Oncol, Herlev, Denmark
Univ Copenhagen, Fac Hlth & Med Sci, Dept Immunol & Microbiol, Copenhagen, Denmark
Green Published, gold, All Open Access, Gold, Green
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