Targeting STAT3 phosphorylation by neem leaf glycoprotein prevents immune evasion exerted by supraglottic laryngeal tumor induced M2 macrophages.

Abstract

Tumor-associated macrophages (TAMs) are preferentially M2 skewed and promote tumor growth, angiogenesis, invasion, and/or metastasis. In this study, we have analyzed the in vitro immunomodulatory potential of a non-toxic neem leaf glycoprotein (NLGP) in reprogramming Stage III supraglottic laryngeal tumor cell lysate (SLTCL) induced M2 TAMs to their classical anti-tumor shape (M1). Data generated from this study support that NLGP is effective in preventing the SLTCL induced generation (CD68(+)CD206(+)IL-10(high) to CD68(+)CD206(-)IL-10(low) TAMs) and functions (NO(low) to NO(high), MHC-I(low) to MHC-I(high), CD80(low) to CD80(high)) of pro-tumorous M2 macrophages, which in turn associated with sustained anti-tumor effector functions by promoting cytotoxic T cell activities and suppressing regulatory T cells. Furthermore, our data also suggest that NLGP prevents M2 skewness of TAMs by downregulating phosphorylation of targeted STAT3.

• Authors: K K Goswami, S Barik, M Sarkar, A Bhowmick, J Biswas, A Bose, R Baral
• Journal: Molecular immunology (Mol Immunol) Vol. 59 Issue 2 Pg. 119-27 (Jun 2014) ISSN: 1872-9142 [Electronic] England
• PMID: 24607970 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Ltd. All rights reserved.

Chemical References

• Glycoproteins
• IL10 protein, human
• Immunologic Factors
• Plant Extracts
• RNA, Small Interfering
• STAT3 Transcription Factor
• STAT3 protein, human
• Interleukin-10
• Interleukin-12
• Nitric Oxide
• NOS2 protein, human
• Nitric Oxide Synthase Type II

Topics

• Azadirachta (chemistry)
• Cell Line, Tumor
• Down-Regulation (drug effects)
• Glycoproteins (pharmacology)
• Humans
• Immune Evasion (drug effects)
• Immunologic Factors (pharmacology)
• Interleukin-10 (biosynthesis)
• Interleukin-12 (biosynthesis)
• Laryngeal Neoplasms (immunology)
• Macrophages (drug effects, immunology)
• Nitric Oxide (biosynthesis)
• Nitric Oxide Synthase Type II (biosynthesis)
• Phosphorylation
• Plant Extracts (pharmacology)
• Plant Leaves (chemistry)
• RNA Interference
• RNA, Small Interfering
• STAT3 Transcription Factor (genetics, metabolism)
• T-Lymphocytes, Cytotoxic (immunology)
• T-Lymphocytes, Regulatory (immunology)