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Open AccessArticle

Immunomodulatory Molecules On Lung Cancer Stem Cells From Lymph Nodes Aspirates

1
Department of Pathology, Medical University of Warsaw, Pawinskiego 7 Street, 02-106 Warsaw, Poland
2
Department of Internal Medicine and Hematology Laboratory of Flow Cytometry, Military Medical Institute, Warsaw, ul. Szaserow 128, 04-141 Warsaw, Poland
3
Department of Internal Medicine, Pulmonology and Allergology, Military Medical Institute, Warsaw, ul. Szaserow 128, 04-141 Warsaw, Poland
4
Department of Internal Medicine, Pulmonary Diseases and Allergy, Medical University of Warsaw, Banacha 1a Street, 02-097 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(4), 838; https://doi.org/10.3390/cancers12040838
Received: 16 March 2020 / Revised: 26 March 2020 / Accepted: 30 March 2020 / Published: 31 March 2020
Over the past decade, immune checkpoint inhibitors have revolutionized the treatment of non-small cell lung cancer (NSCLC). Unfortunately, not all patients benefit from PD-(L)1 blockade, yet, the PD-L1 tumor cell expression is the only approved biomarker, and other biomarkers have been investigated. In the present study, we analyzed the presence of immunomodulatory molecules: PD-L1, CD47, CD73, Fas, and FasL on mature tumor cells (MTCs) and cancer stem cells (CSCs) in lymph nodes (LNs) aspirates and refer it to the lymphocyte subpopulation in peripheral blood (PB). PB samples and LNs aspirates obtained during the endobronchial ultrasound-guided transbronchial needle aspiration (EBUS/TBNA) procedure of 20 patients at different stages of NSCLC. The cells were analyzed by multiparameter flow cytometry. We reported the higher frequency of MTCs and CSCs expressing the investigated immunomodulating molecules in metastatic LNs than in nonmetastatic. The expression of CD47 and PD-L1 was significantly higher on CSCs than on MTCs. Among the lymphocyte subpopulation in PB, we observed a higher frequency of PD-1+ CD8 T cells and Fas+ CD8 T cells in patients with confirmed metastases than in nonmetastatic. Next, we found that the percentage of FasL+ MTCs correlated with the frequency of Fas+ CD3 T cells in LNs aspirates and Fas+ CD8 T cells in PB. Finally, we found that patients with metastatic disease had a significantly higher FasL+/Fas+ MTCs ratio than patients with nonmetastatic disease. Both MTCs and CSCs express different immunomodulatory molecules on their surface. The frequency of FasL+ MTCs associates with altered distribution of Fas+ lymphocyte subpopulations in LNs and PB. View Full-Text
Keywords: lung cancer; cancer stem cells; immune checkpoint inhibitors; EBUS/TBNA lung cancer; cancer stem cells; immune checkpoint inhibitors; EBUS/TBNA
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Raniszewska, A.; Kwiecień, I.; Sokołowski, R.; Rutkowska, E.; Domagała-Kulawik, J. Immunomodulatory Molecules On Lung Cancer Stem Cells From Lymph Nodes Aspirates. Cancers 2020, 12, 838.

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