JUN 27, 2017 07:37 PM PDT

Relieving "Exhausted" Immune Cells To Kill Cancer

WRITTEN BY: Kara Marker

How do T cells become so “exhausted” that they can no longer effectively fight cancer, viruses, bacteria, and other invaders as they are created to do? Scientists from St. Jude Children’s Research Hospital have an answer as well as a way to overcome this exhaustion.

Corresponding author Benjamin Youngblood, PhD with first author Hazem Ghoneim. Credit: Seth Dixon / St. Jude Children's Research Hospital

T cells are key players of the immune system that protect the body from an array of attacks, but when they can’t recognize foreign cells, they can’t direct the immune system to attack. With St. Jude scientists already in the process of designing techniques to rejuvenate T cells, they over the possibility of improving existing immunotherapies to reduce tumor growth, an anti-cancer strategy that relies on boosting the power of the immune system to defend itself.

When immunotherapy doesn’t reach its full potential due to T cell exhaustion, cancer often fails to respond to the treatment, or a patient quickly experiences a relapse of the disease. Researchers believe this failure is due to dysfunction of a process called the “immune checkpoint blockade.”

"The clinical significance of T cell exhaustion is huge, because when a person comes into the clinic with a tumor, it is likely they have had it for many months," explained lead researcher Ben Youngblood, PhD.. "And their T cells, which would be responding to that tumor, have been exposed to the tumor antigen for a long time. This may likely be why immunotherapy fails in many patients, because their T cells are already exhausted or stably repressed."

Youngblood’s proposed solution is based off of preclinical studies of viral infections and growing tumors, indicating a chemotherapy drug called decitabine as capable of bringing exhausted T cells back to life. Plus, the drug is claimed to have the potential to be useful against multiple types of afflictions: HIV in addition to cancer and other pathogens.

"We know the T cells in patients with HIV become exhausted," Youngblood said. "Although there are very effective drugs that reduce the viral load to undetectable levels, that therapy is costly and is not a cure. I'm optimistic that the immune system holds the ultimate promise of a cure for HIV infection, and basic findings such as ours represent one step toward that cure."

But what causes the immune checkpoint to fail leading to T cell exhaustion in the first place? Researchers found that it is an “epigenetic program” that prevented T cells from recognizing tumor cells as abnormal and requiring destruction. The epigenetic program persisted by being passed on through T cell generations. The chemotherapy drug decitabine blocks the epigenetic program preventing T cells from protecting the body from cancer.

"Now that we have shown this is an intrinsic property of T cells, it means you can pull out the T cells, treat them, and reintroduce them to attack the cancer," Youngblood explained. "With such approaches, you limit toxicity to the patient."

The present study was published in the journal Cell.

Source: St. Jude Children’s Research Hospital

About the Author
  • I am a scientific journalist and enthusiast, especially in the realm of biomedicine. I am passionate about conveying the truth in scientific phenomena and subsequently improving health and public awareness. Sometimes scientific research needs a translator to effectively communicate the scientific jargon present in significant findings. I plan to be that translating communicator, and I hope to decrease the spread of misrepresented scientific phenomena! Check out my science blog: ScienceKara.com.
You May Also Like
NOV 13, 2019
Health & Medicine
NOV 13, 2019
European Respiratory Society Task Force Sarcoidosis Patient Survey
Sarcoidosis is a rare, granulomatous disease that is found in the lungs of 90% of people diagnosed, but it can affect any organ in the body. More than 2/3 ...
NOV 13, 2019
Drug Discovery & Development
NOV 13, 2019
Aspirin Combats Tuberculosis
Tuberculosis is a global infection far from being eradicated. It currently infects more than 1,400 people per year in Australia. The deadliest form and exp...
NOV 13, 2019
Immunology
NOV 13, 2019
The C-word. Michael Kinch's new book and the future of Cancer Treatment
The C-word. Dare we say it? Is a cure for cancer within reach?   Professor Michael Kinch https://publichealth.wustl.edu/scholars/michael-s-kinch/ of W...
NOV 13, 2019
Drug Discovery & Development
NOV 13, 2019
The Three Drugs that Reverse Biological Aging
In the last 100 years, life expectancy in the US has risen from 55 years until 79 (Roser: 2019). And with the continuous development of medicine and scie...
NOV 13, 2019
Immunology
NOV 13, 2019
Your Immune Response Varies from AM to PM
“My biological clock is ticking.” We’ve heard people say this phrase - maybe even said it ourselves - but what do we mean exactly? Often...
NOV 13, 2019
Immunology
NOV 13, 2019
Treating Alzheimer's? Target Microglia
The body’s own immune cells may be the common denominator in Alzheimer’s disease. In a new study of the relationship between microglia, tau pro...
Loading Comments...