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Calreticulin exposure on malignant blasts correlates with improved natural killer cell-mediated cytotoxicity in acute myeloid leukemia patients
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SYSNO ASEP 0537960 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Calreticulin exposure on malignant blasts correlates with improved natural killer cell-mediated cytotoxicity in acute myeloid leukemia patients Tvůrce(i) Truxová, I. (CZ)
Kašíková, L. (CZ)
Šálek, C. (CZ)
Hensler, M. (CZ)
Lysák, D. (CZ)
Holicek, P. (CZ)
Bílková, P. (CZ)
Holubová, M. (CZ)
Chen, X. (US)
Mikyšková, Romana (UMG-J) RID
Reiniš, Milan (UMG-J) RID
Kovář, Marek (MBU-M) RID, ORCID
Tomalová, Barbora (MBU-M) ORCID
Kline, J.P. (US)
Galluzzi, L. (US)
Špíšek, R. (CZ)
Fučíková, J. (CZ)Celkový počet autorů 17 Zdroj.dok. Haematologica-The Hematology Journal. - : Fondazione Ferrata Storti - ISSN 0390-6078
Roč. 105, č. 7 (2020), s. 1868-1878Poč.str. 11 s. Forma vydání Online - E Jazyk dok. eng - angličtina Země vyd. IT - Itálie Klíč. slova nk cells ; dendritic cells ; tumor-cells ; immunity ; death ; expression ; growth ; cancer ; il-15 Vědní obor RIV EB - Genetika a molekulární biologie Obor OECD Immunology Vědní obor RIV – spolupráce Mikrobiologický ústav - Mikrobiologie, virologie Způsob publikování Open access Institucionální podpora UMG-J - RVO:68378050 ; MBU-M - RVO:61388971 UT WOS 000550445700017 DOI 10.3324/haematol.2019.223933 Anotace In some settings, cancer cells responding to treatment undergo an immunogenic form of cell death that is associated with the abundant emission of danger signals in the form of damage-associated molecular patterns. Accumulating preclinical and clinical evidence indicates that danger signals play a crucial role in the (re-)activation of antitumor immune responses in vivo, thus having a major impact on patient prognosis. We have previously demonstrated that the presence of calreticulin on the surface of malignant blasts is a positive prognostic biomarker for patients with acute myeloid leukemia (AML). Calreticulin exposure not only correlated with enhanced T-cell-dependent antitumor immunity in this setting but also affected the number of circulating natural killer (NK) cells upon restoration of normal hematopoiesis. Here, we report that calreticulin exposure on malignant blasts is associated with enhanced NK cell cytotoxic and secretory functions, both in AML patients and in vivo in mice. The ability of calreticulin to stimulate NK-cells relies on CD11c(+)CD14(high) cells that, upon exposure to CRT, express higher levels of IL-15R alpha, maturation markers (CD86 and HLA-DR) and CCR7. CRT exposure on malignant blasts also correlates with the upregulation of genes coding for type I interferon. This suggests that CD11c(+)CD14(high) cells have increased capacity to migrate to secondary lymphoid organs, where can efficiently deliver stimulatory signals (IL-15R alpha/IL15) to NK cells. These findings delineate a multipronged, clinically relevant mechanism whereby surface-exposed calreticulin favors NK-cell activation in AML patients. Pracoviště Ústav molekulární genetiky Kontakt Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Rok sběru 2021 Elektronická adresa https://haematologica.org/article/view/9938
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