Evaluation of the involvement of the innate immune response mediated by TLR2 and TLR4 in the therapeutic response to dacarbazine in melanoma murine model

• Grant number: 07/07037-6
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: May 01, 2008
• End date: June 30, 2009
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Roger Chammas
• Grantee: Cláudia Beatriz Nedel Mendes de Aguiar
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 98/14247-6 - Center for Research on Cell-Based Therapy, AP.CEPID

Abstract

Melanoma is one of the most invading and deathly forms of skin cancer. In addition, this kind of tumor presents an extraordinary chemoresistance, which could explain the discouraging results observed in the treatment of this disease. In spite of this, the drug more utilized in the treatment of melanoma is dacarbazine. Tumoral cells can develop mechanisms to escape of immunosurveillance by a process called immunoediting. In this process the tumor suffers a selective pressure which leads to the malignant progression. Thus, tumoral microenvironment modifications may stimulate the immune system, contributing in this way to the tumoral eradication. The blockade of the toll-like receptors (TLRs), combined with treatments based on chemotherapy drugs, reduces different kinds of cancer, including melanoma. In this study, wild type and knockout for TLR2 and TLR4 C57B1/6 mice will receive implants of melanoma B16-F10 cells and will be treated with dacarbazine. The responses of these receptors to dacarbazina and the repopulation rate of tumoral cells after the treatment will be evaluated. Distinguishing genes expression in these conditions and the presence of hypoxia areas in the tumor will also be studied. The development of tools that associate the use of chemotherapy drugs with elements of the immune system is crucial to the cancer treatment. Therefore, the study of the effects of immunotherapy combined with dacarbazine treatment on TLRs is of extreme relevance in the search of therapies aiming the combat of the malignant melanoma.