TY - JOUR

T1 - Patients With Myeloproliferative Neoplasms Harbor High Frequencies of CD8 T Cell-Platelet Aggregates Associated With T Cell Suppression

AU - Carnaz Simões, Ana Micaela

AU - Holmström, Morten Orebo

AU - Aehnlich, Pia

AU - Rahbech, Anne

AU - Radziwon-Balicka, Aneta

AU - Zamora, Carlos

AU - Wirenfeldt Klausen, Tobias

AU - Skov, Vibe

AU - Kjær, Lasse

AU - Ellervik, Christina

AU - Fassi, Daniel El

AU - Vidal, Silvia

AU - Hasselbalch, Hans Carl

AU - Andersen, Mads Hald

AU - thor Straten, Per

N1 - Publisher Copyright: Copyright © 2022 Carnaz Simões, Holmström, Aehnlich, Rahbech, Radziwon-Balicka, Zamora, Wirenfeldt Klausen, Skov, Kjær, Ellervik, Fassi, Vidal, Hasselbalch, Andersen and thor Straten.

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

KW - CALR mutation

KW - JAK2 mutation

KW - Myeloproliferative Neoplasms (MPN)

KW - platelet-bound T cells

KW - platelet-T cell aggregates

KW - platelets

UR - https://www.frontiersin.org/articles/10.3389/fimmu.2022.970322/full

U2 - 10.3389/fimmu.2022.866610

DO - 10.3389/fimmu.2022.866610

M3 - Journal article

C2 - 35603202

AN - SCOPUS:85130739125

VL - 13

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 866610

ER -