The Tricky Way Gastric Cancer Evades The Immune System

Gastric cancer cells have an altered pattern of gene expression which helps them hide from the immune system.

AsianScientist (May 2, 2017) – A team of scientists from Singapore has identified over 2,000 locations were gastric cancer cells have mutations that can alter the expression of genes. These findings, published in Cancer Discovery, shed light on how cancers evade the immune system and could prove applicable to other cancers.

“Epigenetics is a process by which a cell’s DNA is chemically modified by the environment, to change gene expression. By comparing the epigenetic profiles of gastric tumors to normal tissues from the same patient, we were able to identify those promoters specifically altered in gastric cancer tissues,” explained team leader Professor Patrick Tan, Deputy Executive Director of the Biomedical Research Council at the Agency for Science, Technology and Research (A*STAR).

Promoters are regions in the genome that regulate the expression of genes, similar to the switch of a light bulb. Just like how a light can be controlled by multiple switches to influence its intensity and colour, the team identified hundreds of genes controlled by multiple promoters, causing alternate versions of that gene to be produced.

Strikingly, the team also found that many of these alternate gene variants produced in gastric tumors were also less likely to stimulate the immune system compared with their normal counterparts. They used Nano-ChIPseq, a platform developed in Singapore that enables the comprehensive identification of promoter elements using small amounts of tissue.

“Our data, combining computational, experimental assays, and analyses of human gastric cancers, indicates that the use of these less immunogenic variants may enhance the ability of a tumor to bypass the host’s immune system. This process is referred to as tumor immunoediting,” added Ms. Aditi Qamra, graduate student at the Genome Institute of Singapore and first author of this study.

The team’s results suggest that studying the promoter profiles of tumors may possibly identify those patients who would be responsive to immunotherapy. Moreover, the team also identified cellular pathways required by the tumor cell to maintain expression of the less immunogenic gene variants.

The team is now exploring if targeting these pathways, combined with immunotherapy, can increase the proportion of patients that might respond to such drugs. The team is also working with ETPL, the commercialization arm of A*STAR, to develop the Nano-ChIPseq platform into a start-up, so that the platform is made available to more academic and industry customers.


The article can be found at: Qamra et al. (2017) Epigenomic Promoter Alterations Amplify Gene Isoform and Immunogenic Diversity in Gastric Adenocarcinoma.

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Source: A*STAR; Photo: Shutterstock.
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