title: 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.affiliation: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata, 700026, India.
authors.forename: K K
authors.initials: KK
authors.lastname: Goswami
authors.affiliation: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata, 700026, India.
authors.forename: S
authors.initials: S
authors.lastname: Barik
authors.affiliation: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata, 700026, India.
authors.forename: M
authors.initials: M
authors.lastname: Sarkar
authors.affiliation: Department of ENT and Head-Neck Oncology, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata, 700026, India.
authors.forename: A
authors.initials: A
authors.lastname: Bhowmick
authors.affiliation: Department of Surgical Oncology and Medical Oncology, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata 700026, India.
authors.forename: J
authors.initials: J
authors.lastname: Biswas
authors.affiliation: Department of Molecular Medicine, Bose Institute, C.I.T. Scheme, Kolkata, India.
authors.forename: A
authors.initials: A
authors.lastname: Bose
authors.affiliation: Department of Immunoregulation and Immunodiagnostics, Chittaranjan National Cancer Institute (CNCI), 37, S. P. Mukherjee Road, Kolkata, 700026, India. Electronic address: rathindranath.baral@cnci.org.in.
authors.forename: R
authors.initials: R
authors.lastname: Baral
mesh_terms: D031601:Azadirachta / Q000737:chemistry*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000494:pharmacology*; D006801:Humans; D057131:Immune Evasion / Q000187:drug effects*; D007155:Immunologic Factors / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D007822:Laryngeal Neoplasms / Q000276:immunology*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry*; D034622:RNA Interference; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D006023:Glycoproteins; C508609:IL10 protein, human; D007155:Immunologic Factors; D010936:Plant Extracts; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D016753:Interleukin-10; D018664:Interleukin-12; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II
keywords: Neem leaf glycoprotein; Supraglottic laryngeal tumor cell lysate; T cells; Tumor-associated macrophages