Neem leaf glycoprotein salvages T cell functions from Myeloid-derived suppressor cells-suppression by altering IL-10/STAT3 axis in melanoma tumor microenvironment.
Melanoma Res
; 31(2): 130-139, 2021 04 01.
Article
em En
| MEDLINE
| ID: mdl-33625102
ABSTRACT
Myeloid-derived suppressor cells (MDSCs) suppress antitumor immune functions. We have observed that an immunomodulator, neem leaf glycoprotein (NLGP), inhibits tumor-resident MDSCs and enhances antitumor CD8+ T cell immunity. NLGP inhibits the number as well as functions of tumor-resident MDSCs (Gr1±CD11b±) and enhances antitumor CD8± T cell immunity by downregulating arginase 1 and inducible nitric oxide synthase production in MDSCs. Accordingly, decreased T cell anergy and helper to regulatory T cell conversion have been observed in the presence of NLGP, which ultimately augments T cell functions. Mechanistically, NLGP-mediated rectification of T cell suppressive functions of MDSCs was primarily associated with downregulation of the interleukin (IL)-10/signal transducer and activator of transcription 3 (STAT3) signaling axis within the tumor microenvironment, as confirmed by knockdown of STAT3 (by STAT3-siRNA) and using IL-10-/- mice. Thus, NLGP-mediated suppression of MDSC functions in tumor hosts is appeared to be another associated effective mechanism for the eradication of murine melanoma by NLGP.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas
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Linfócitos T
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Interleucina-10
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Folhas de Planta
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Azadirachta
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Fator de Transcrição STAT3
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Microambiente Tumoral
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Melanoma Res
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2021
Tipo de documento:
Article