Nav: Home

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer

April 04, 2019

TAMPA, Fla. - The immune system is an important defender against cancer. Immune cells continuously search the body for disease and use their anti-tumor cell properties to target and destroy defective cells. However, most cancer patients have an impaired immune system that allows cancer cells to go undetected. Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

"The impaired T cell function present in most cancer patients is a primary reason cancer cells can evade protective antitumor immunity, and it represents a major limitation in the development of new immunotherapies," said Paulo Rodriguez, Ph.D., associate member of the Department of Immunology at Moffitt.

In a new study, published in Nature Communications, Moffitt scientists investigated how the immune system becomes dysfunctional, with the hope that a better understanding of these mechanisms may lead to improved treatment strategies.

Previous studies have shown that the protein Chop is involved in cellular stress responses and myeloid immune cell responses. The Moffitt team wanted to determine if Chop also plays a role in T cell immunity. They discovered that Chop expression is higher in T cells from ovarian cancer patients than in healthy ovarian tissue. They also found that high nuclear levels of Chop in CD8+ tumor infiltrating T cells in ovarian cancer patients were associated with poor clinical responses. This suggests that Chop may be involved in altered immune responses to cancer.

In order to determine the function of Chop in T cells, the researchers conducted an extensive set of laboratory experiments with mice and primary murine and human T cells. They found that Chop plays an important role in negatively regulating T cell responses, and that Chop levels increase when T cells become activated. This increase is dependent on the protein Perk that is involved in stress responses. When the researchers deleted the Chop gene in T cells, anti-tumor CD8+ T cell immunity was improved and T cell-based immunotherapy treatments were more effective in immunologically relevant mouse models.

These observations suggest that under normal circumstances, Chop plays an important role in helping to balance anti-tumor T cell responses. However, tumors have learned to hijack the normal function of Chop to decrease T cell immunity. A less active immune system permits cancer cells to bypass the anti-tumor immunity function of T cells, resulting in continued cancer cell growth and development.

"Our results demonstrate the primary role of Chop in the impaired activity of CD8+ T cells in tumors and suggest it is possible to overcome tumor-induced CD8+ T cell suppression and increase the efficacy of T cell-based immunotherapy by blocking Chop or ER stress," said Jose Conejo-Garcia, M.D., Ph.D., chair of Moffitt's Department of Immunology.
-end-
The study was supported by grants from the National Institutes of Health, including a National Cancer Institute Cancer Center Support Grant, and the Department of Defense.

About Moffitt Cancer Center

Moffitt is dedicated to one lifesaving mission: to contribute to the prevention and cure of cancer. The Tampa-based facility is one of only 50 National Cancer Institute-designated Comprehensive Cancer Centers, a distinction that recognizes Moffitt's scientific excellence, multidisciplinary research, and robust training and education. Moffitt is a Top 10 cancer hospital and has been nationally ranked by U.S. News & World Report since 1999. Moffitt devotes more than 2 million square feet to research and patient care. Moffitt's expert nursing staff is recognized by the American Nurses Credentialing Center with Magnet® status, its highest distinction. With more than 6,000 team members, Moffitt has an economic impact in the state of $2.5 billion. For more information, call 1-888-MOFFITT (1-888-663-3488), visit MOFFITT.org, and follow the momentum on Facebook, Twitter and YouTube.

H. Lee Moffitt Cancer Center & Research Institute

Related Cancer Articles:

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
Radiotherapy for invasive breast cancer increases the risk of second primary lung cancer
East Asian female breast cancer patients receiving radiotherapy have a higher risk of developing second primary lung cancer.
More Cancer News and Cancer Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#541 Wayfinding
These days when we want to know where we are or how to get where we want to go, most of us will pull out a smart phone with a built-in GPS and map app. Some of us old timers might still use an old school paper map from time to time. But we didn't always used to lean so heavily on maps and technology, and in some remote places of the world some people still navigate and wayfind their way without the aid of these tools... and in some cases do better without them. This week, host Rachelle Saunders...
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.