Dialing back treg cell function boosts the body's cancer-fighting immune activity

August 18, 2013

By carefully adjusting the function of crucial immune cells, scientists may have developed a completely new type of cancer immunotherapy—harnessing the body's immune system to attack tumors. To accomplish this, they had to thread a needle in immune function, shrinking tumors without triggering unwanted autoimmune responses.

The new research, performed in animals, is not ready for clinical use in humans. However, the approach, making use of a key protein to control immune function, lends itself to further study using candidate drugs that employ the same mechanisms.

"This preclinical study demonstrates proof of principle that using a drug to regulate the function of a special, immunosuppressive subset of so-called T-regulatory (Treg) cells safely controls tumor growth," said study leader Wayne W. Hancock, M.D., Ph.D., of the Division of Transplant Immunology at The Children's Hospital of Philadelphia (CHOP). "It really moves the field along towards a potentially major, new ."

Hancock and colleagues published the study today in Nature Medicine.

"There's a basic paradox in immunology: why doesn't the immune system prevent cancer in the first place?" said Hancock. The answer is complicated, he adds, but much of it involves a delicate among elements of the immune system: while immunity protects us against disease, an overly aggressive may trigger dangerous, even life-threatening, autoimmune reactions in which the body attacks itself.

In the current study, Hancock focused on a subtype of called Foxp3+ Tregs, for short. Tregs were already known to limit autoimmunity, but often at the cost of curtailing immune responses against tumors. "We needed to find a way to reduce Treg function in a way that permits antitumor activity without allowing autoimmune reactions," he said.

Hancock's group showed that inhibiting the enzyme p300 can affect the functions of another protein, Foxp3, which plays a key role in controlling the biology of Tregs. By deleting the gene that expresses p300, the researchers safely reduced Treg function and limited in mice. Notably, they also achieved the same effects on p300 and Tregs in mice by using a drug that inhibits p300 in normal mice.

Hancock will pursue further investigations into targeting p300 in immunotherapy. The preclinical findings offer encouraging potential for being translated into the clinic, said Hancock, who added that pharmaceutical companies have expressed interest in researching this approach as a possible cancer therapy.

The antitumor study, down-regulating Treg function, is the flip side of another part of Hancock's Treg research. In a 2007 animal study, also in Nature Medicine, he increased Treg function with the goal of suppressing the immune response to allow the body to better tolerate organ transplants. In the current study, decreasing Treg activity permitted the to attack an unwelcome visitor—a tumor. In both cases, he relied on epigenetic processes—using groups of chemicals called acetyl groups to modify key proteins—but in opposite directions. "This is the yin and yang of ," he added.

Explore further: New insight into immune tolerance furthers understanding of autoimmune disease

More information: Yujie Liu et al., "Inhibition of p300 impairs Foxp3+ T regulatory cell function and promotes antitumor immunity," Nature Medicine, published online Aug. 18, 2013. doi.org/10.1038/nm.3286

Related Stories

New insight into immune tolerance furthers understanding of autoimmune disease

September 15, 2011
It is no easy task to preserve the delicate balance that allows us to maintain a strong immune system that can defend us from harmful pathogens, but that is sensitive enough to correctly identify and spare our own cells. ...

In clinical trial, scientists hope to train immune system to attack cancer

June 10, 2013
(Medical Xpress)—Training our immune systems to fight cancer is an appealing prospect. Why wouldn't we want to launch our own internal army against one of our most-hated foes? But the process is a bit like learning to spot ...

Traffic cops of the immune system: Molecule called IKBNS in charge of regulatory immune cell maturation

November 29, 2012
A certain type of immune cell—the regulatory T cell, or Treg for short—is in charge of putting on the brakes on the immune response. In a way, this cell type might be considered the immune system's traffic cops.

Protein complex linked to cancer growth may also help fight tumors, researchers say

July 22, 2013
Researchers at Moffitt Cancer Center and Tianjin Medical University Cancer Institute and Hospital in China have discovered a gene expression signature that may lead to new immune therapies for lung cancer patients. They found ...

Self-regulation of the immune system suppresses defense against cancer

December 21, 2011
Regulatory T cells, which are part of the body's immune system, downregulate the activity of other immune cells, thus preventing the development of autoimmune diseases or allergies. Scientists at the German Cancer Research ...

Mechanism offers promising new approach for harnessing the immune system to fight cancer

August 4, 2013
St. Jude Children's Research Hospital scientists have discovered a way to target the immune system to shrink or eliminate tumors in mice without causing autoimmune problems. Researchers also found evidence that the same mechanism ...

Recommended for you

Does your child really have a food allergy?

July 24, 2017
(HealthDay)—Many people misunderstand what food allergies are, and even doctors can be confused about how to best diagnose them, suggests a new report from the American Academy of Pediatrics.

Genetic immune deficiency could hold key to severe childhood infections

July 18, 2017
A gene mutation making young children extremely vulnerable to common viruses may represent a new type of immunodeficiency, according to a University of Queensland researcher.

What are the best ways to diagnose and manage asthma?

July 18, 2017
What are the best ways to diagnose and manage asthma in adults? This can be tricky because asthma can stem from several causes and treatment often depends on what is triggering the asthma.

Large multi-ethnic study identifies many new genetic markers for lupus

July 17, 2017
Scientists from an international consortium have identified a large number of new genetic markers that predispose individuals to lupus.

Study finds molecular explanation for struggles of obese asthmatics

July 17, 2017
A large, bouquet-shaped molecule called surfactant protein A, or SP-A, may explain why obese asthma patients have harder-to-treat symptoms than their lean and overweight counterparts, according to a new study led by scientists ...

Team identifies potential cause for lupus

July 14, 2017
Leading rheumatologist and Feinstein Institute for Medical Research Professor Betty Diamond, MD, may have identified a protein as a cause for the adverse reaction of the immune system in patients suffering from lupus. A better ...

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.