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Preparation of Myeloid Derived Suppressor Cells MDSC from Naive and Pancreatic Tumor-bearing Mice using Flow Cytometry and Automated Magnetic Activated Cell Sorting AutoMACS
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Mn complex-mediated enhancement of antitumor response through modulating myeloid-derived suppressor cells in

Satyajit Das1, Kaushik Banerjee1, Susmita Roy2

  • 1Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, Kolkata, India.

In Vivo (Athens, Greece)
|September 6, 2014
PubMed
Abstract

Insights

Mn-N-(2-hydroxyacetophenone) glycinate (MnNG) enhances anti-tumor immunity by modulating the tumor microenvironment. It reduces suppressive myeloid-derived suppressor cells and promotes T-helper 1 cell responses, improving cancer therapy efficacy.

Area of Science:

  • Immunology
  • Cancer Biology
  • Pharmacology

Background:

  • The tumor microenvironment (TME) often confers resistance to chemotherapy.
  • Developing effective immunomodulators for cancer therapy remains a challenge.

Purpose of the Study:

  • To investigate the immunomodulatory effects of Mn-N-(2-hydroxyacetophenone) glycinate (MnNG) on the tumor microenvironment.
  • To assess MnNG's potential as an anti-cancer therapeutic agent.

Main Methods:

  • Assessed myeloid-derived suppressor cells (MDSCs) and Cluster of Differentiation 4 (Cd4)(+) T-cells (secreting Interferon-γ [Ifnγ] and Interleukin-4 [Il4]) using annexin V-binding assay.
  • Evaluated T-cell proliferation via in vitro co-culture assay and flow cytometry in a drug-resistant TME.
  • Analyzed MDSC differentiation, co-stimulatory molecule expression, and T-helper cell 1 (Th1) response.

Main Results:

  • MnNG treatment increased Ifnγ-secreting Cd4(+) T-cell infiltration and decreased MDSC numbers in vivo.
  • MnNG modulated MDSC differentiation into dendritic cells, up-regulating co-stimulatory molecules and reversing MDSC suppressive functions.
  • Co-culture of Cd4(+) T-cells with MDSCs showed reduced Il4 and enhanced Ifnγ expression after MnNG treatment.

Conclusions:

  • MnNG effectively modulates MDSC differentiation towards dendritic cells within the drug-resistant TME.
  • MnNG enhances the T-helper cell 1 (Th1) immune response, demonstrating significant immunomodulatory efficacy.
Keywords:
MDRMn complexTh1 responseimmunomodulationmyeloid derived suppressor cells

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