title: Mn complex-mediated enhancement of antitumor response through modulating myeloid-derived suppressor cells in drug-resistant tumor.
abstract: BACKGROUND
  The tumor microenvironment (TME) renders tumor cells more resistant to chemotherapy. However, effective immunomodulators for cancer therapy are still elusive. We hypothesized that Mn-N-(2-hydroxyacetophenone) glycinate (MnNG), reported to be an antitumor agent, can modulate the TME.
  
  
  METHODS
  Immunomodulatory effects of MnNG were performed through assessing Myeloid Derived Suppressor Cells (MDSCs), Interferon-γ (Ifnγ)- and Interleukin-4 (Il4)-secreting Cluster of Differentiation 4 (Cd4)(+) T-cells by annexin V-binding assay in drug-resistant TME and T-cell proliferation following in vitro co-culture assay by flow cytometry.
  
  
  RESULTS
  MnNG induced infiltration of Ifnγ-secreting Cd4(+) T-cells and reduces MDSC numbers in vivo. Furthermore, it modulated differentiation of MDSCs towards dendritic cells with up-regulation of co-stimulatory molecules and reversed the suppressive function of MDSC's that enhances T-helper cell 1 (Th1) response. MnNG treatment resulted in reduced expression of IL4, but enhanced expression of Ifnγ when Cd4(+) T-cells were co-cultured with MDSCs.
  
  
  CONCLUSIONS
  MnNG modulates MDSCs differentiaton towards dendritic cells and enhances Th1 response in drug-resistant TME, leading to immunomodulatory efficacy.
authors.affiliation: Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, Kolkata, India.
authors.forename: Satyajit
authors.initials: S
authors.lastname: Das
authors.affiliation: Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, Kolkata, India.
authors.forename: Kaushik
authors.initials: K
authors.lastname: Banerjee
authors.affiliation: Department of Pharmacology, Institute of Postgraduate Medical Education and Research, Kolkata, India.
authors.forename: Susmita
authors.initials: S
authors.lastname: Roy
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, India.
authors.forename: Saikat
authors.initials: S
authors.lastname: Majumder
authors.affiliation: Department of Pharmacology, Institute of Postgraduate Medical Education and Research, Kolkata, India.
authors.forename: Mitali
authors.initials: M
authors.lastname: Chatterjee
authors.affiliation: Division of Molecular Medicine, Bose Institute, Kolkata, India.
authors.forename: Subrata
authors.initials: S
authors.lastname: Majumdar
authors.affiliation: Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, Kolkata, India soumitra01@yahoo.com.
authors.forename: Soumitra Kumar
authors.initials: SK
authors.lastname: Choudhuri
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm; D005260:Female; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology*; D056747:Immunomodulation / Q000187:drug effects*; D016130:Immunophenotyping; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D022423:Myeloid Cells / Q000187:drug effects* / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D007155:Immunologic Factors; D008345:Manganese
keywords: MDR; Mn complex; Th1 response; immunomodulation; myeloid derived suppressor cells