Establishment of an immune response against Melanoma cancer may depend on the capacity of dendritic cells to transfer tumor Antigens (Ags) into T cell-rich areas.
Most Melanoma tumors are accepted by the host’s immune system and progress even when they contain potentially antigenic proteins. Analysis of this response may help to understand how most tumors escape immune rejection. Overexpression of the anti-apoptotic protein Bcl-2 in Melanoma cells prevented the development of an antitumor immune response. This suggested that induction of a specific immune response involved the release of antigenic proteins from tumor cells undergoing apoptosis.
O6-methylguanine DNA-methyltransferase (MGMT enzyme) overexpression in melanoma cells also induces resistance to Chemotherapy. This increased DNA-repair activity in tumor cells has been associated with resistance to treatment to DNA-directed drugs, while defects in DNA repair pathways result in hypersensitivity to these agents. In the past years the unraveling of the molecular basis of these DNA pathways, with a better understanding of the DNA damage caused by different anticancer agents, has provided the rationale for the use of some DNA repair inhibitors to optimize the therapeutic use of DNA-damaging agents currently used in the treatment of tumors. In addition, the possibility to specifically target the differences in DNA repair capacity between normal and tumor cells has recently emerged as an exciting possibility.
In a model using melanoma cells in mice, phagocyting cells were observed to be attracted at the injection site and ingest tumor cell fragments. It has been recently demonstrated that dendritic cells selectively recognized and captured apoptotic cells and cell fragments liberated following apoptosis. Moreover, antigenic proteins that were contained in apoptotic bodies and engulfed by dendritic cells were shown to be 1–10,000 times more efficient in generating MHC-peptide complexes than preprocessed peptides.
So with all this in mind, we need the tumor to shed some antigenic proteins/fragments to be used by the Antigen Presenting Cells. (APCs) undergoing apoptosis.
There are three types of APCs:
1) Macrophages
2) Dendritic cells
3) B cells
This was one of last pieces of my puzzle that I will share wth you soon.
I am so excited, I hope I can get some sleep.
Jimmy B
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