What You Really Need to Know about Cancer

Monday, November 17, 2014

How cancer cells escape from our natural immune system?

How cancer cells escape from our natural immune system?
Our natural immune system plays an essential role in targeting cancer cells for destruction and elimination. Even though, tumor cells are smarter than our immune system and
have developed ways to avoid immune detection.

Immune selection 

At the very beginning of a tumor development, the amount of antigen may be too few to stimulate the immune system and due to the speedy proliferation of malignant cells, the immune system is quickly overwhelmed.

Antigen modulation

Tumors can initially express antigens to which the immune system responds but lose them by antibody-induced internalization or antigenic variation.

Low immunogenicity

Lack of Neo-antigens

Some tumors are lack of having peptides of novel proteins that can be presented by MHC molecules, and therefore they appear normal to the immune system.

Lack of co-stimulatory Molecules

Most of the tumors do not express co-stimulatory proteins, which are essential to activate naive T cells.

Lack of class I MHC

Some tumors have lost one or more MHC molecules, which are obligatory to activate naive T cells. Faults in mechanisms of MHCI production can render the cancer cells “unseen” to CD8 cells.

Tumors shed their neo-antigens

Some types of tumors may shed their unique antigens which block antibodies and T cells from reacting with malignant cells.

Immune suppression by tumor cells or T regulatory cells 

Some tumors may evade the immune system by secreting immunosuppressive molecules (such as TGF-ß,IL-10)  and others by inducing suppressor cells.

Recent developments

Lung cancer tumors suppress Natural Killer cells functions

Recently, a team of researchers led by Julie Y. Djeu, Ph.D., associate center director of education and training at Moffitt, found that TGF-β synthesized by tumor cells causes NK cells to make high levels of a molecule called microRNA-183 (miR-183). MicroRNAs are important regulators of gene expression. They bind to genetic components called RNA and target them for destruction.

Researchers found that miR-183 binds to the RNA for a protein called DAP12, resulting in significantly lower levels of DAP12 in NK cells. DAP12 plays a critical role in activating the NK cells' cytotoxic pathways; therefore, lower levels of DAP12 in NK cells results in a reduced ability to target tumor cells.

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