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This Week in Cancer Research: Aug 24, 2011

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In Cancer Research this week, researchers in Europe and Japan write that the inflammatory cytokine interleukin-18 induces immunosuppression in cancer. The team shows that low levels of circulating IL-18 act to suppress the NK cell function of tumor immunosurveillance. "IL-18 produced by tumor cells promotes the development of NK-controlled metastases in a PD-1-dependent manner. Accordingly, PD-1 is expressed by activated mature NK cells in lymphoid organs of tumor bearers and is upregulated by IL-18," the authors write. In addition, the team found that RNAi-mediated knockdown of IL-18 was sufficient to stimulate NK cell-dependent immunosurveillance in various tumor models. "Our findings suggest novel clinical implementations of anti-PD-1 antibodies in human malignancies that produce IL-18," the team adds.

Also in Cancer Research this week, researchers at Cardiff University in the UK explore a novel tumor antigen derived from an enhanced degradation of Bax proteins, which limit apoptosis in human cancers. The antigen the team generated was able to recognize and kill a variety of human leukocyte antigen-matched cancer cells, including primary cancer cells from chronic lymphocytic leukemia. In addition, the team found that because the antigen was generated using Bax proteins, the antigen's reactivity corresponded with the proteasomal degradation of Bax protein in cancer cells. "Taken together, our findings suggest a new concept for tumor antigens based on regulatory proteins that are ubiquitously expressed in normal cells, but that have abnormally enhanced degradation in cancer cells," the authors write. "Bax degradation products offer candidate immune antigens in cancers such as CLL in which increased Bax degradation correlates with poor clinical prognosis."

And finally in Cancer Research this week, US researchers report a novel G protein-coupled receptor, GPR56, which they say regulates VEGF production and angiogenesis during the progression of melanoma. GPR56 inhibits VEGF production from melanoma cell lines and impedes growth of the disease, the team adds. "Consistent with its suppressive roles in melanoma progression, the expression levels of GPR56 are inversely correlated with the malignancy of melanomas in human subjects," the authors add. "We propose that components of the GPR56-mediated signaling pathway may serve as new targets for antiangiogenic treatment of melanoma."

The Scan

Researchers Develop Polygenic Risk Scores for Dozens of Disease-Related Exposures

With genetic data from two large population cohorts and summary statistics from prior genome-wide association studies, researchers came up with 27 exposure polygenic risk scores in the American Journal of Human Genetics.

US Survey Data Suggests Ancestry Testing Leads Way in Awareness, Use of Genetic Testing Awareness

Although roughly three-quarters of surveyed individuals in a Genetics in Medicine study reported awareness of genetic testing, use of such tests was lower and varied with income, ancestry, and disease history.

Coral Genome Leads to Alternative Amino Acid Pathway Found in Other Non-Model Animals

An alternative cysteine biosynthesis pathway unearthed in the Acropora loripes genome subsequently turned up in sequences from non-mammalian, -nematode, or -arthropod animals, researchers report in Science Advances.

Mosquitos Genetically Modified to Prevent Malaria Spread

A gene drive approach could be used to render mosquitos unable to spread malaria, researchers report in Science Advances.