Study reveals new role for Hippo pathway in suppressing cancer immunity

December 1, 2016, University of California - San Diego
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

Researchers discover novel mechanism linking changes in mitochondria to cancer cell death

February 20, 2018
To stop the spread of cancer, cancer cells must die. Unfortunately, many types of cancer cells seem to use innate mechanisms that block cancer cell death, therefore allowing the cancer to metastasize. While seeking to further ...

Stem cell vaccine immunizes lab mice against multiple cancers

February 15, 2018
Stanford University researchers report that injecting mice with inactivated induced pluripotent stem cells (iPSCs) launched a strong immune response against breast, lung, and skin cancers. The vaccine also prevented relapses ...

Induced pluripotent stem cells could serve as cancer vaccine, researchers say

February 15, 2018
Induced pluripotent stem cells, or iPS cells, are a keystone of regenerative medicine. Outside the body, they can be coaxed to become many different types of cells and tissues that can help repair damage due to trauma or ...

Team paves the way to the use of immunotherapy to treat aggressive colon tumors

February 15, 2018
In a short space of time, immunotherapy against cancer cells has become a powerful approach to treat cancers such as melanoma and lung cancer. However, to date, most colon tumours appeared to be unresponsive to this kind ...

Can our genes help predict how women respond to ovarian cancer treatment?

February 15, 2018
Research has identified gene variants that play a significant role in how women with ovarian cancer process chemotherapy.

First comparison of common breast cancer tests finds varied accuracy of predictions

February 15, 2018
Commercially-available prognostic breast cancer tests show significant variation in their abilities to predict disease recurrence, according to a study led by Queen Mary University of London of nearly 800 postmenopausal women.

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.