Previous studies have identified the Hippo pathway kinases LATS1/2 as a tumor suppressor, contrary to that researchers from University of California reveal a surprising role for these enzymes in subduing cancer immunity.
Published in the journal Cell, the findings could have a clinical role in improving efficiency of immunotherapy drugs. "Before our study, no one knew that the Hippo pathway was regulating immunogenicity," said first author Toshiro Moroishi. Adding, "LATS1/2 deletion in cancer cells improves tumor immunogenicity, leading to the destruction of cancerous cells by enhancing anti-tumor immune responses."
‘Inhibiting LATS1/2 could be an attractive approach to treat cancer. LATS is an ideal target because there are many kinase inhibitors that have been successfully developed as cancer drugs.’
Hippo pathway signaling regulates organ size by moderating cell growth, apoptosis and stem cell renewal but dysregulation contributes to cancer development. In vitro studies of Hippo pathway kinases LATS1/2 showed that the loss of these enzymes promoted cell proliferation and tumor survival. In vivo research using immune-compromised mouse models also supports a tumor suppressor function of the Hippo pathway.
However, when Moroishi and team deleted LATS1/2 from mouse cancer cells and examined tumor growth in models with healthy immune systems researchers found that immunogenicity -- the ability to stimulate an immune response -- improved, destroying cancer cells. Researchers caution that immune systems of mouse models are different from the human immune system so the response might be different and further studies are needed.
If the outcome proves to be the same, using a LATS1/2 inhibitor alone or in combination with an immune checkpoint inhibitor may stimulate the immune system of patients that previously did not respond to immunotherapy treatments. Currently, most immunotherapy research focuses on targeting the immune system, but the new findings reveal that tumor cells may also be vulnerable to inhibitors.
"Inhibiting LATS1/2 could be an attractive approach to treat cancer," said Kun-Liang Guan. Adding, "LATS is an ideal target because there are many kinase inhibitors that have been successfully developed as cancer drugs."