CXCR4 Inhibition Counteracts Immunosuppressive Properties of Metastatic NSCLC Stem Cells.
5'-Nucleotidase
/ genetics
B7-H1 Antigen
/ genetics
CD8-Positive T-Lymphocytes
/ immunology
Carcinoma, Non-Small-Cell Lung
/ immunology
Cell Movement
Gene Expression Regulation, Neoplastic
Humans
Immune Tolerance
Lung Neoplasms
/ immunology
Neoplasm Metastasis
Neoplastic Stem Cells
/ physiology
Receptors, CXCR4
/ antagonists & inhibitors
T-Lymphocytes, Regulatory
/ immunology
Tumor Cells, Cultured
Tumor Escape
Tumor Microenvironment
Tumor-Associated Macrophages
/ immunology
CD73
CXCR4
PD-L1
adenosine
immunosuppression
metastasis initiating cells
non-small cell lung cancer
tumor associated macrophage (TAM)
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2020
2020
Historique:
received:
21
03
2020
accepted:
10
08
2020
entrez:
30
10
2020
pubmed:
31
10
2020
medline:
27
5
2021
Statut:
epublish
Résumé
Cancer stem cells (CSCs) are functionally defined as the cell subset with greater potential to initiate and propagate tumors. Within the heterogeneous population of lung CSCs, we previously identified highly disseminating CD133+CXCR4+ cells able to initiate distant metastasis (metastasis initiating cells-MICs) and to resist conventional chemotherapy. The establishment of an immunosuppressive microenvironment by tumor cells is crucial to sustain and foster metastasis formation, and CSCs deeply interfere with immune responses against tumors. How lung MICs can elude and educate immune cells surveillance to efficiently complete the metastasis cascade is, however, currently unknown. We show here in primary tumors from non-small cell lung cancer (NSCLC) patients that MICs express higher levels of immunoregulatory molecules compared to tumor bulk, namely PD-L1 and CD73, an ectoenzyme that catalyzes the production of immunosuppressive adenosine, suggesting an enhanced ability of MICs to escape immune responses. To investigate
Identifiants
pubmed: 33123122
doi: 10.3389/fimmu.2020.02168
pmc: PMC7566588
doi:
Substances chimiques
B7-H1 Antigen
0
CXCR4 protein, human
0
Receptors, CXCR4
0
5'-Nucleotidase
EC 3.1.3.5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
02168Informations de copyright
Copyright © 2020 Fortunato, Belisario, Compagno, Giovinazzo, Bracci, Pastorino, Horenstein, Malavasi, Ferracini, Scala, Sozzi, Roz, Roato and Bertolini.
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