Myeloid derived suppressor cells are not elevated in monoclonal gammopathies

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F65269705%3A_____%2F21%3A00074945" target="_blank" >RIV/65269705:_____/21:00074945 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S2152265021022096" target="_blank" >https://www.sciencedirect.com/science/article/pii/S2152265021022096</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/S2152-2650(21)02209-6" target="_blank" >10.1016/S2152-2650(21)02209-6</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Myeloid derived suppressor cells are not elevated in monoclonal gammopathies

Popis výsledku v původním jazyce

Background The immunologically tolerant microenvironment may support a development of malignant multiple myeloma (MM) from precancerous monoclonal gammopathy of undetermined significance (MGUS) and blocks the efficacy of immunotherapy in existing MM as well. Myeloid derived suppressor cells (MDSC) represent heterogeneous group of cells with immunosuppressive activity and capability of promotion of tumor growth in MM. Their increased number and negative effect was described in MM but usually not in other monoclonal gammopathies (MGs). Aim Identification and enumeration of MDSC subsets in different MG subjects and comparison of their number with healthy controls. Methods Whole peripheral blood of 30 newly diagnosed and untreated MGs (2 MGUS, 7 MM with AL amyloidosis and 21 MM) and 13 healthy controls was used. Incubation with combination of MoAbs CD16/CD15/HLA-DR/CD14/CD45/CD11b/CD33/CD66b was done. Samples were analysed on BD FACSCanto II (BD Biosciences) after NH4Cl lysis and reanalysed with Infinicyt SW (Cytognos). Results Whole leukocytes were distributed into subpopulations using progressive gating strategy allowing detection of MDSC derived from granulocytes (G-MDSC) and monocytes (M-MDSC) with elimination of dendritic cells (DCs) and other contaminating cells (basophils etc.). There were found no differences in M- and G-MDSC relative and absolute count when compared whole MG group and controls. Even selection of MG with GREATER-THAN OR EQUAL TO95 % clonal plasma cells (PCs) or MGs with presence of circulating PCs or MGs with &gt;30 g/l monoclonal Id protein did not show statistically different values of both MDSC subsets in comparison with control samples. The only statistically different value was decreased number of DCs in MGs. Conclusion Although elevated levels of MDSC in MM were previously published, this study did not prove it probably due to the different gating procedure. However, it was able to clearly define all leukocyte subsets in peripheral blood, thus only higher numbers of dublets may affect the final count of MDSC. Interestingly, low density neutrophils and tumor associated neutrophils should not be easily distinguish from MDSC, so their better characterization is needed in the future. The isolation and verification of MDSC immunosuppressive potential should be the next step in their analyses.

Název v anglickém jazyce

Myeloid derived suppressor cells are not elevated in monoclonal gammopathies

Popis výsledku anglicky

Background The immunologically tolerant microenvironment may support a development of malignant multiple myeloma (MM) from precancerous monoclonal gammopathy of undetermined significance (MGUS) and blocks the efficacy of immunotherapy in existing MM as well. Myeloid derived suppressor cells (MDSC) represent heterogeneous group of cells with immunosuppressive activity and capability of promotion of tumor growth in MM. Their increased number and negative effect was described in MM but usually not in other monoclonal gammopathies (MGs). Aim Identification and enumeration of MDSC subsets in different MG subjects and comparison of their number with healthy controls. Methods Whole peripheral blood of 30 newly diagnosed and untreated MGs (2 MGUS, 7 MM with AL amyloidosis and 21 MM) and 13 healthy controls was used. Incubation with combination of MoAbs CD16/CD15/HLA-DR/CD14/CD45/CD11b/CD33/CD66b was done. Samples were analysed on BD FACSCanto II (BD Biosciences) after NH4Cl lysis and reanalysed with Infinicyt SW (Cytognos). Results Whole leukocytes were distributed into subpopulations using progressive gating strategy allowing detection of MDSC derived from granulocytes (G-MDSC) and monocytes (M-MDSC) with elimination of dendritic cells (DCs) and other contaminating cells (basophils etc.). There were found no differences in M- and G-MDSC relative and absolute count when compared whole MG group and controls. Even selection of MG with GREATER-THAN OR EQUAL TO95 % clonal plasma cells (PCs) or MGs with presence of circulating PCs or MGs with &gt;30 g/l monoclonal Id protein did not show statistically different values of both MDSC subsets in comparison with control samples. The only statistically different value was decreased number of DCs in MGs. Conclusion Although elevated levels of MDSC in MM were previously published, this study did not prove it probably due to the different gating procedure. However, it was able to clearly define all leukocyte subsets in peripheral blood, thus only higher numbers of dublets may affect the final count of MDSC. Interestingly, low density neutrophils and tumor associated neutrophils should not be easily distinguish from MDSC, so their better characterization is needed in the future. The isolation and verification of MDSC immunosuppressive potential should be the next step in their analyses.

Druh

O - Ostatní výsledky

CEP obor

—

OECD FORD obor

30200 - Clinical medicine

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

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