The effects of mesenchymal stem cells on the IDO, HLA-G and PD-L1 expression of breast tumor cells MDA-MB-231 and MCF-7

Yıl 2019, Cilt: 4 Sayı: 3, 132 - 137, 01.12.2019

Rabia Bilge Özgül Özdemir Alper Tunga Özdemir , Cengiz Kırmaz , Mehmet İbrahim Tuğlu , Özgür Şenol , Cenk Serhan Özverel , Afig Berdeli

https://doi.org/10.25000/acem.601633

Cited By: 2

Öz

Aim:
Mesenchymal stem cells (MSCs) are strong immunomodulatory cells and a component
of the tumor microenvironment. In this study, we aimed to investigate the
effects of MSCs derived from adipose tissue on the expressions of immune
evasive molecules indoleamine 2,3-dioxygenase (IDO), human leukocyte antigen G
(HLA-G) and programmed death-ligand 1 (PD-L1) of breast tumor cell lines
MDA-MB-231 and MCF-7. 

Methods:
For this purpose, MSCs, MDA-MB-231 and MCF-7 cells were cultured with increased
doses of interferon gamma (IFN-g). In another plate, tumor cells were cultured
in transwell inserts using the same IFN-g stimulation to evaluate the effect of
MSCs. At the end of the culture period, the HLA-G and PD-L1 expression was
detected by flow cytometry, and IDO expression by the Luminex method.

Results:
We found that in low-dose IFN-g stimulation (10 ng/mL), MSCs led to a
significant increase in the HLA-G and PD-L1 expression of MCF-7 cells. On the
contrary, at a high dose of IFN-g (50 ng/mL), their expression significantly
decreased in both tumor cells. In addition, we observed that the IDO expression
of MDA-MB-231 cells was significantly increased in the presence of MSCs, but
MCF-7 cells were not affected.

Conclusion:
In conclusion, for MDA-MB-231 cells, MSCs may play a protective role because they
reduce the expression of HLA-G and PD-L1 that are involved in the suppression
of cytotoxic cells and exhaustion of T cells. On the other hand, MSCs may be an
important source of high IDO levels, and therefore may negatively affect the
antitumor immune response. However, our data should be supported by further
studies.

Anahtar Kelimeler

Mesenchymal stem cells, immune evasion, HLA-G, PD-L1, IDO

Destekleyen Kurum

Manisa Celal Bayar University, Scientific Research Projects Coordination Unit

Proje Numarası

2017-224

Teşekkür

We would like to thank the Dr. Ayşe Nalbantsoy for the help of the flow cytometry analyzes.

Mezenkimal kök hücrelerin, meme tümörü hücreleri MDA-MB-231 ve MCF-7’nin IDO, HLA-G ve PD-L1 ifadeleri üzerine etkileri

Öz

Amaç: Mezenkimal kök hücreler (MKH) güçlü
immünomodülatör hücreleridir ve ayrıca tümör mikroçevresinin bir bileşenidir.
Bu çalışmada meme tümör hücre hatları MDA-MB-231 ve MCF-7’nin immün evazif
moleküller olan Indoleamine 2,3-dioxygenase (IDO), Human Leukocyte Antigen G
(HLA-G) and Programmed Death-Ligand 1 (PD-L1) ifadelerine yağ dokusu kökenli
mezenkimal kök hücrelerin etkilerini araştırmayı amaçladık.

Yöntemler: Bu amaçla MKH, MDA-MB-231 ve MCF-7
hücrelerini artan dozlarda interferon gama (IFN-g) ile kültüre edildi. Başka
bir kültür kabında MKH’ler ile tümör hücreleri trans-well insertler ve aynı
IFN-g uyarımı ile kültür edildi. Kültür süresinin bitiminde HLA-G ve PD-L1
ifadeleri flow-sitmotetri yöntemi ile IDO ifadeleri Luminex yöntemi ile analiz
edildi.

Bulgular: Düşük dozlu IFN-g uyarımında (10 ng/mL),
MSC'lerin MCF-7 hücrelerinin HLA-G ve PD-L1 ekspresyonunda önemli bir artışa
yol açtığını bulduk. Aksine, yüksek doz IFN-g ile (50 ng/mL) bu ifadelerin her
iki tümör hücresinde de önemli ölçüde azaldığını gördük. Ek olarak, MDA-MB-231
hücrelerinin IDO ekspresyonunun MSC'lerin varlığında anlamlı şekilde arttığını,
ancak MCF-7 hücrelerinin etkilenmediği gördük.

Sonuç: Sonuç olarak, MDA-MB-231 hücreleri için
MSC'ler, sitotoksik hücrelerin baskılanmasında ve T hücrelerinin tükenmesinde
önemli bir rol oynayan HLA-G ve PD-L1 ekspresyonunu azalttığı için koruyucu bir
rol oynayabilir. Öte yandan, MSC'ler yüksek IDO seviyeleri için önemli bir
kaynak olabilir ve bu nedenle anti-tümör immün yanıtı olumsuz yönde etkileyebilir.
Bununla birlikte, verilerimiz diğer çalışmalarla desteklenmelidir.

Anahtar Kelimeler

Mezenkimal kök hücreler, immün kaçınma, HLA-G, PD-L1, IDO

Proje Numarası

2017-224

Kaynakça

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