Drug combination may improve impact of immunotherapy in head and neck cancer

September 21, 2017, University of California - San Diego
The combination therapy with TLR agonist and anti-PD-1 agent activates CD8+ T cells (red) in the tumors. Credit: UC San Diego Health

Checkpoint inhibitor-based immunotherapy has been shown to be very effective in recurrent and metastatic head and neck cancer but only in a minority of patients. University of California San Diego School of Medicine researchers may have found a way to double down on immunotherapy's effectiveness.

In a paper published in the journal JCI Insights on September 21, researchers report that a combination of toll-like receptors (TLR) agonists—specialized proteins that initiate immune to foreign pathogens or, in this case, cancer —and other immunotherapies injected directly into a suppresses tumor growth throughout the whole body.

"The mechanism reverses the phenotype of a tumor by changing its inherit properties to make the tumor more immunogenic," said Ezra E.W. Cohen, MD, professor of medicine at UC San Diego School of Medicine and associate director for translational science at UC San Diego Moores Cancer Center and senior author on the paper. "In this study, the combination of immunotherapy drugs resulted in the complete elimination of cancer cells and even when re-challenged the tumors did not recur."

Macrophages are specialized that destroy targeted cells. They are supposed to present antigens to the immune system to get it started, but in cancer they stop doing that so the immune system is unable to recognize the cancer. The combination of drugs restored the ability of macrophages to initiate a tumor response and allow the immune system to eliminate the cancer.

To improve the efficiency of checkpoint inhibitor immunotherapy on human papillomavirus-negative and HPV-positive head and neck cancers, the team of researchers combined synthetic TLR7 and TLR9 that were developed by Dennis Carson, MD, Professor Emeritus at UC San Diego School of Medicine, with an inhibitor of the protein called programmed death-1 receptor (PD-1) which is responsible for turning off T cells.

TLR agonists cause an innate immune response—that is, the rapid response to a foreign substance in the body. This immediate protection comes at a cost since the nonspecific immune response may harm healthy cells if activation of the immune systems persists. PD-1 inhibitors stimulate an adaptive response calling on B cells and T cells to respond to a specific target, but this process takes longer to go into effect.

In mouse models, the combined TLR agonists and PD-1 inhibitors injected directly into a tumor incited a tumor-specific response by T cells which prevented metastasis or the spread of the cancer. When cancer had already spread, the TLR and anti-PD-1 combo eliminated the primary tumor as well as distant tumors. The combination therapy was more effective than either agent alone.

The next step should be to study these drugs in a clinical setting for head and using FDA-approved immunotherapy. In addition, Cohen suggests studying these agents with other combinations such as chemotherapy and radiation therapy.

"As we make the tumor more immunogenic we should be making other therapies more effective and eliminate the completely," said Cohen.

Explore further: Study sheds light on why some breast cancers have limited response to immunotherapy

More information: JCI Insights, DOI: 10.1172/jci.insight93397

Related Stories

Study sheds light on why some breast cancers have limited response to immunotherapy

August 21, 2017
UNC Lineberger Comprehensive Cancer Center researchers have identified a possible reason why some aggressive breast cancers are unresponsive to certain immunotherapy treatments, as well as a potential solution.

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 ...

Checkpoint inhibitors fire up different types of T cells to attack tumors

August 10, 2017
Cancer immunotherapies that block two different checkpoints on T cells launch immune attacks on cancer by expanding distinct types of T cell that infiltrate tumors, researchers from The University of Texas MD Anderson Cancer ...

Identifying a novel target for cancer immunotherapy

April 12, 2017
Targeting a molecule called B7-H4—which blocks T-cells from destroying tumor cells—could lead to the development of new therapies that boost the immune system's ability to fight cancer, according to a review published ...

Study reveals new role for Hippo pathway in suppressing cancer immunity

December 1, 2016
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 ...

Shedding light on cause of resistance to tumor immunotherapy

July 25, 2017
In tumor immunotherapy, the body's own defense system is activated against the tumor cells. However, for the majority of patients, the tumor cells become resistant to the treatments used. Researchers at the University of ...

Recommended for you

Research shows possible new target for immunotherapy for solid tumors

April 24, 2018
Research from the University of Cincinnati (UC) reveals a potential new target to help T cells (white blood cells) infiltrate certain solid tumors.

Changes in breast tissue increase cancer risk for older women

April 24, 2018
Researchers in Norway, Switzerland, and the United States have identified age-related differences in breast tissue that contribute to older women's increased risk of developing breast cancer. The findings, published April ...

Targeting molecules called miR-200s and ADAR2 could prevent tumor metastasis in patients with colorectal cancer

April 24, 2018
Colorectal cancer is the third most common cancer worldwide and the third-leading cause of cancer-related deaths. The main cause of death in patients with colorectal cancer is liver metastasis, with nearly 70% of patients ...

Experimental arthritis drug prevents stem cell transplant complication

April 24, 2018
An investigational drug in clinical trials for rheumatoid arthritis prevents a common, life-threatening side effect of stem cell transplants, new research from Washington University School of Medicine in St. Louis shows. ...

Scientists develop a new model for glioblastoma using gene-edited organoids

April 24, 2018
Glioblastoma multiforme (GBM) is an incredibly deadly brain cancer and presents a serious black box challenge. It's virtually impossible to observe how these tumors operate in their natural environment and animal models don't ...

Removing the enablers: Reducing number of tumor-supporting cells to fight neuroblastoma

April 24, 2018
Investigators at the Children's Center for Cancer and Blood Diseases at Children's Hospital Los Angeles provide preclinical evidence that the presence of tumor-associated macrophages—a type of immune cell—can negatively ...

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.