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. * Dr. Anamika Bose and Dr. Rathindranath Baral contributed equally to the writing of this article. Received 7 November 2020 Accepted 12 January 2021 Correspondence to Rathindranath Baral, PhD, Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37 S.P. Mukherjee Road, Kolkata 700026, India, Tel: +91 033 2476 5101 ext. 334; fax: +91 033 2475 7606; e-mail: baralrathin@hotmail.com; rathindranath.baral@cnci.org.in Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.
No comments:
Post a Comment