Immunomodulation of anti-tumor immune response by dendritic cells stimulated with chemical and biological substances

Author: kakha mchedlishvili
Keywords: prostate, cancer, carcinoma, dendritic cell, DC, Treg, MHC II class, CD80, CD86, CD40, CD11c, CD205, MHC I, CD4, CD25, 5-azacytidine, lenalidomide, RM1, immunotherapy, immunomodulation, C57BL/6, cell culture
Annotation:

Though the benefits of therapy have been shown in clinical trials, the underlying immune mechanisms responsible for the outcomes have not been completely elucidated. With clinical research confirming the benefits of combination therapy over monotherapy, it has become more important than ever to define the effects each drug has upon the immune system and the target malignancy so that new regimens might be created to maximize efficacy and minimize side effects. To research the role of dendritic cells in cancer imunopathogenesis and enhancement of anti-tumor immune response by stimulation is one of the actual direction in cancer research scientific groups. Immunomodulatory drugs are being used with increasing frequency to treat various cancers. And although some of the greatest advancements have been achieved in the treatment of hematologic malignancies, a growing body of evidence exists to suggest a benefit in the treatment of solid organ tumors, including prostate cancer. As our understanding of tumor immunology has evolved, the role for immunotherapy in the treatment of malignancy has evolved as well. Today we already have data how to treat hematologic malignisation, myeloma and other types of cancer with immunomodulatory drugs. Researches show effects of 5-azacitidin and Lenalidomid on T lymphocytes and natural killers, but there is no data about effects on dendritic cells. Also, they has not been used together in prostate cancer treatment yet. Aim of our project was to determine anti-tumoral effects of dendritic cells stimulated with imunomodulatory drugs, such as 5-azacitidine and Lenalidomide. Results of this research suggest enhancement of antigen presentation by dendritic cells. Expression rate of the molecules (MHC II, CD40, CD80, CD86, CD205, MHC I)which play main role in this process was raced by 10%. Treg cells where detected to decrease in number by 34%. Referring this results we can suppose that immunotherapy with 5-azacytidine and Lenalidomide can be used to enhance anti-tumor immune response.

Lecture files:

ანტისიმსივნური იმუნური პასუხის იმუნომოდულაცია დენდრიტული უჯრედების ქიმიური და ბიოლოგიური პრეპარატებით სტიმულაციით [ka]