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Angiotensin II contributes to intratumoral immunosuppressionvia induction of PD-L1 expression in non-small cell lung carcinoma.
- Source :
-
International immunopharmacology [Int Immunopharmacol] 2020 Jul; Vol. 84, pp. 106507. Date of Electronic Publication: 2020 Apr 24. - Publication Year :
- 2020
-
Abstract
- The formation of an immunosuppressive microenvironment and up-regulation of PD-L1 protein are the main causes of tumor immune escape. Previous reports suggest that Angiotensin II (Ang II) can modulate the immune status of tumor microenvironment in non-small cell lung cancer (NSCLC), but the underlying mechanism remains not fully understood. Here we demonstrated that AngII treatment causes the reduction of intratumoral infiltrating CD4 T lymphocytes in tumor-bearing mice, increases the accumulation of immunosuppressive granulocytes and TAMs in tumor tissue, and upregulates the expression levels of immunosuppressive marker genes. In addition, AngII/AGTR1 axis triggers cell PD-L1 expression through a mechanism involving increases in PD-L1 mRNA stability by human antigen R (HuR), an AU-rich element (ARE)-binding protein. Collectively, AngII/AGTR1 signaling promotes the tumor immunosuppressive microenvironment by upregulating PD-L1 in NSCLC, the mechanism of which is largely accounted by HuR-mediated PD-L1 mRNA stabilization.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
B7-H1 Antigen genetics
Cell Line
Humans
Lymphocytes, Tumor-Infiltrating immunology
Male
Mice, Inbred C57BL
RNA, Messenger
Tumor Microenvironment immunology
Angiotensin II immunology
B7-H1 Antigen immunology
Carcinoma, Non-Small-Cell Lung immunology
Immune Tolerance
Lung Neoplasms immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1878-1705
- Volume :
- 84
- Database :
- MEDLINE
- Journal :
- International immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 32339920
- Full Text :
- https://doi.org/10.1016/j.intimp.2020.106507