Neem leaf glycoprotein salvages T cell functions from Myeloid-derived suppressor cells-suppression by altering IL-10/STAT3 axis in melanoma tumor microenvironment

被引：4

作者：

Sarkar, Madhurima ^{[1
]}

Bhuniya, Avishek ^{[1
]}

Ghosh, Sarbari ^{[1
]}

Sarkar, Anirban ^{[1
]}

Saha, Akata ^{[1
]}

Dasgupta, Shayani ^{[1
]}

Bera, Saurav ^{[1
]}

Chakravarti, Mohona ^{[1
]}

Dhar, Sukanya ^{[1
]}

Guha, Ipsita ^{[1
]}

Ganguly, Nilanjan ^{[1
]}

Das, Tapasi ^{[1
]}

Banerjee, Saptak ^{[1
]}

Pal, Smarajit ^{[2
]}

Ghosh, Swapan Kr ^{[3
]}

Bose, Anamika ^{[1
]}

Baral, Rathindranath ^{[1
]}

机构：

[1] Chittaranjan Natl Canc Inst, Dept Immunoregulat & Immunodiagnost, Kolkata, India

[2] Chittaranjan Natl Canc Inst, Dept Clin Biochem, Kolkata, India

[3] Ramakrishna Mission Vivekananda Centenary Coll, Dept Bot, Kolkata, India

来源：

MELANOMA RESEARCH | 2021年 / 31卷 / 02期

关键词：

interleukin-10; melanoma; myeloid derived suppressor cells; neem leaf glycoprotein; STAT3;

D O I：

10.1097/CMR.0000000000000721

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：130 / 139

页数：10

共 23 条

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