Tumor metastasis leads to the overwhelming incidences of mortality in cancer patients and poses the great challenge for cancer therapy. Such diffuse tumor cell display usual antigens that can’t be recognized by body’s immune system . Therefore, to awaken immune cells to spontaneously reject metastatic tumors, many scientists make some progress in finding key molecular brakes in immune cells. In light of recent findings and future promises, immunotherapy has been chosen as scientific breakthrough of the year 2013 by the journal Science.
Some “Brake” molecules in the innate and adaptive immune system
Researchers from the Institute of Molecular Biotechnology (IMBA) of the Austrian Academy of Sciences (OeAW), in collaboration with researchers in Australia and Germany, demonstrated that a molecule called Cbl-b acts as a molecular brake for Natural Killer Cells to reject cancer. Deletion or targeted inactivation of Cbl-b efficiently enhanced the anti-tumor function of NK cells. As a result the progression of metastases in melanoma and breast cancer was significantly inhibited.
In the adaptive immune system, CTLA-4 functions as a molecular brake by preventing T-cell activation. Yervoy (ipilimumab) was developed to specifically binds to and blocks it. When Yervoy releases the brake , T cells are free to destroy tumors. Still, the promising aspects of Yervoy prompts researchers to look at other potential target molecules. For example, PD-1 as a brake protein gradually has became a research focus, by which some cancers use to deactivate the group of T cells that surrounds the tumor.
Immunotherapy against cancer types.
So far, researchers have focused on melanoma and kidney cancer because they responded best to immunotherapies in early trials, and are thought to be particularly visible to the immune system. However, some cancers such as liver cancer may still pose a challenge to immunotherapy approaches. Additionally , breast, colorectal, pancreatic and ovarian cancers are also particularly adept at suppressing immune cells says Lisa Butterfield, a cancer researcher at the University of Pittsburgh in Pennsylvania. Combination therapies, she thinks, may be applied to overcome these limitations.
Reference :
1. The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. Nature, 2014; DOI: 10.1038/nature12998
2. Cancer treatment: The killer within. Nature. 2014 Apr 3;508(7494):24-6.