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Dendritic cell vaccination augments the profile of tumor infiltrating Natural Killer cells in tumor bearing mice
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  • Marcia Michelin,
  • Eduardo Arthur Rodovalho Alves,
  • Polyana Silva,
  • Eddie Murta
Marcia Michelin
Universidade Federal do Triangulo Mineiro

Corresponding Author:[email protected]

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Eduardo Arthur Rodovalho Alves
Universidade Federal do Triângulo Mineiro
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Polyana Silva
Universidade Federal do Triangulo Mineiro
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Eddie Murta
Federal University of Triangulo Mineiro
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Abstract

Assessing the Natural Killer (NK) cells in Dendritic Cell (DC) vaccine immunotherapy of 4T1 cell-induced breast cancer in Balb/C mice, we watch the expression of killer activation receptors NKp46, NKG2D, and inhibitory killer cell immunoglobulin-like receptor (KIR) Ly49G2, NKG2A/C/E and the interleukins (IL) 2, 10, 12, 17, tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ). 30 Balb/C mice divided into untreated, or control experimental group (GI), untreated induced tumor group (GII), and the DC treated vaccine-induced tumor group (GIII). Bone marrow from donor mice was collected to produce the vaccine. The 25-day experiment comprised tumor volume measurements and at the end of the treatment protocol mice were euthanized for removal of the spleen and evaluation of tumor infiltration by flow cytometry of the receptors NKp46, NKG2D, Ly49G2 and NKG2A/C/E and the cytokines. Our results showed that mice treated with the DC vaccine reduced the expression of inhibition receptors Ly49G2D/NKG2A/C/E in the spleen and tumor infiltrate (p=0.0001), with increased fluorescence intensity of splenic IL-10, IL-2, IL-12, IL-17, TNF-α and IFN-γ-producing NKp46/NKG2D cells (p=0.0001), intratumoral TNF-α and IFN-γ-producing by NKp46/NKG2D cells (p=0.0001). We demonstrated that immunotherapy with DC can alter the profile of NK cells by directly influencing them into an antitumor response due to reduced expression of inhibition receptors and increased production of cytokines such as IL-2, IL-12, TNF-α and IFN-γ by cells. Also, the activation of receptors confers NK cells the ability to reverse tumor-induced immunosuppression, stimulating the immune system to eliminate tumor cells.