Calreticulin exposure on malignant blasts correlates with improved natural killer cell-mediated cytotoxicity in acute myeloid leukemia patients

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388971%3A_____%2F20%3A00537960" target="_blank" >RIV/61388971:_____/20:00537960 - isvavai.cz</a>

Alternative codes found

RIV/68378050:_____/20:00537960 RIV/00216208:11110/20:10402482 RIV/00216208:11130/20:10402482 RIV/00216208:11140/20:10402482 and 3 more

Result on the web

<a href="https://haematologica.org/article/view/9938" target="_blank" >https://haematologica.org/article/view/9938</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3324/haematol.2019.223933" target="_blank" >10.3324/haematol.2019.223933</a>

Result language

angličtina

Original language name

Calreticulin exposure on malignant blasts correlates with improved natural killer cell-mediated cytotoxicity in acute myeloid leukemia patients

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10606 - Microbiology

Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Haematologica-The Hematology Journal

ISSN

0390-6078

e-ISSN

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Volume of the periodical

105

Issue of the periodical within the volume

7

Country of publishing house

IT - ITALY

Number of pages

11

Pages from-to

1868-1878

UT code for WoS article

000550445700017

EID of the result in the Scopus database

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