New Mechanism Explains How Tumor Cells Escape Immune System Attack

By LabMedica International staff writers
Posted on 15 Dec 2016

Despite the commonly accepted role of the Hippo pathway kinase enzymes LATS1/2 (large tumor suppressor 1 and 2) as tumor suppressors, a recent study found evidence that they actually helped cancer cells to avoid being targeted by the body's immune system.

Poorly immunogenic tumor cells evade host immunity and grow even in the presence of an intact immune system, but the complex mechanisms regulating tumor immunogenicity have not been elucidated. In an endeavor to explain how tumor cells escape attack by the immune system, investigators at the University of California, San Diego (USA) worked with three different mouse tumor models.

Image: The micrograph on the left is of melanoma cells growing in a mouse model. On the right, arrows point to immune cells infiltrating a tumor with LATS1/2 deleted (Photo courtesy of the University of California, San Diego).

They reported in the December 1, 2016, issue of the journal Cell that loss of the Hippo pathway kinases LATS1/2 in tumor cells inhibited tumor growth. Tumor regression by LATS1/2 deletion required adaptive immune responses, and LATS1/2 deficiency enhanced tumor vaccine efficacy. Mechanistically, LATS1/2-null tumor cells secreted nucleic-acid-rich extracellular vesicles, which induced a type I interferon response.

The investigators noted that immune systems of mouse models differ from the human immune system so the results obtained in this study might be different and further work is needed.

"Inhibiting LATS1/2 could be an attractive approach to treat cancer," said senior author Dr. Kun-Liang professor of pharmacology at the University of California, San Diego. "LATS is an ideal target because there are many kinase inhibitors that have been successfully developed as cancer drugs."

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University of California, San Diego