Source: Columbia University Medical Center
Summary: Researchers have found that the response of an immune system to the immune therapy drugs depends on individual’s genetic makeup.
When DNA inside the cells is mutated, leads to cancer cells which are recognized by the immune system as ‘foreign’. But cancer cells have found many ways to escape detection by the immune system. Some of the new drugs (immune checkpoint inhibitors) can help the immune system to detect cancer cells and lead to striking responses in a number of cancer types. Researchers from Columbia University Medical Center and Memorial Sloan Kettering Cancer Center have found that the response of an immune system to the immune therapy drugs depends on individual’s genetic makeup. The genes which play a role belong to the human leukocyte antigen (HLA) system. The study findings were published in the journal Science.
The HLA gene complex encodes proteins which are used by the immune system to recognize which cells belong in the body and which do not. Many possible variations of HLA genes are observed which allows a person’s immune system to react to a wide range of foreign invaders. The study was conducted on 1,535 cancer patients who were treated with immune checkpoint inhibitors and found that patients who had more versions of HLA genes responded better to the therapy and patients with a combination of low HLA diversity and fewer tumor mutations did not do well with immune checkpoint inhibitors. Finally, the research team showed certain HLA patterns affected survival as well, a pattern that also has been observed in patients with autoimmune disease. The result findings may help for the design of neoantigen-based therapeutic vaccines.
Dr. Naiyer Rizvi said, “The relationship between HLA and outcomes to immune checkpoint inhibitors is important for many reasons. It is another piece of the immunotherapy puzzle-who responds and why. It also may be relevant for understanding side effects observed with immunotherapy, and this is an area we are currently exploring.”
More Information: Diego Chowell et al, “Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy”, Science (2017). DOI: 10.1126/science.aao4572