Study reveals new role for Hippo pathway in suppressing cancer immunity

December 1, 2016
The image 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. Credit: UC San Diego Health

Previous studies identified the Hippo pathway kinases LATS1/2 as a tumor suppressor, but new research led by University of California San Diego School of Medicine scientists reveals a surprising role for these enzymes in subduing cancer immunity. The findings, published in Cell on December 1, 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, MD, PhD, postdoctoral researcher at UC San Diego Moores Cancer Center. "LATS1/2 deletion in improves tumor immunogenicity, leading to the destruction of cancerous cells by enhancing anti-tumor immune responses."

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 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 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 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, PhD, Distinguished Professor of Pharmacology at Moores Cancer Center and senior author of the study. "LATS is an ideal target because there are many kinase inhibitors that have been successfully developed as cancer drugs."

Explore further: Researchers show how a targeted drug overcomes suppressive immune cells

More information: Cell, DOI: 10.1016/j.cell.2016.11.005

Related Stories

Researchers show how a targeted drug overcomes suppressive immune cells

November 9, 2016
A Ludwig Cancer Research study shows that an experimental drug currently in clinical trials can reverse the effects of troublesome cells that prevent the body's immune system from attacking tumors. The researchers also establish ...

Study suggests that autophagy inhibitors could improve efficacy of chemotherapies

October 24, 2016
Chemotherapies treat cancer by killing tumor cells, but certain types of chemotherapy can also drive an immune system response to target and destroy the remaining tumor cells.

Immune suppressor cells identified for advanced prostate cancer

December 21, 2015
Immune suppressor cells called MDSCs (myeloid-derived suppressor cells) may be important in developing treatments for advanced prostate cancer, according to a study at The University of Texas MD Anderson Cancer Center.

Mechanism of an effective MEK inhibitor identified

November 1, 2016
Understanding the effects of certain targeted therapies on antitumor immunity is necessary to design combined interventions for more effective cancer treatment. In the past, data have shown that trametinib, an FDA-approved ...

Histone deacetylase inhibitors enhance immunotherapy in lung cancer models, researchers say

March 31, 2016
Several new immunotherapeutic antibodies that inhibit checkpoint receptors on T cells to restimulate the immune system to target tumors have been approved to treat advanced stage lung cancer and melanoma; however, only 20 ...

Killer T cells recognize cancer in pre-clinical tumors, but are silenced as tumor develops

August 9, 2016
One of the challenges for developing truly successful immunotherapies is that cancer is a wily foe for the immune system. Tumors have multiple lines of defense against our immune cells' attempts to attack them. Although our ...

Recommended for you

Scientists develop blood test that spots tumor-derived DNA in people with early-stage cancers

August 16, 2017
In a bid to detect cancers early and in a noninvasive way, scientists at the Johns Hopkins Kimmel Cancer Center report they have developed a test that spots tiny amounts of cancer-specific DNA in blood and have used it to ...

Toxic formaldehyde is produced inside our own cells, scientists discover

August 16, 2017
New research has revealed that some of the toxin formaldehyde in our bodies does not come from our environment - it is a by-product of an essential reaction inside our own cells. This could provide new targets for developing ...

Cell cycle-blocking drugs can shrink tumors by enlisting immune system in attack on cancer

August 16, 2017
In the brief time that drugs known as CDK4/6 inhibitors have been approved for the treatment of metastatic breast cancer, doctors have made a startling observation: in certain patients, the drugs—designed to halt cancer ...

Popular immunotherapy target turns out to have a surprising buddy

August 16, 2017
The majority of current cancer immunotherapies focus on PD-L1. This well studied protein turns out to be controlled by a partner, CMTM6, a previously unexplored molecule that is now suddenly also a potential therapeutic target. ...

Researchers find 'switch' that turns on immune cells' tumor-killing ability

August 16, 2017
Molecular biologists led by Leonid Pobezinsky and his wife and research collaborator Elena Pobezinskaya at the University of Massachusetts Amherst have published results that for the first time show how a microRNA molecule ...

A metabolic treatment for pancreatic cancer?

August 15, 2017
Pancreatic cancer is now the third leading cause of cancer mortality. Its incidence is increasing in parallel with the population increase in obesity, and its five-year survival rate still hovers at just 8 to 9 percent. Research ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.