Boosting T cell 'memory' may result in longer-lasting and effective responses for patients

April 16, 2018, University of Texas M. D. Anderson Cancer Center
Scanning electron micrograph of a human T lymphocyte (also called a T cell) from the immune system of a healthy donor. Credit: NIAID

Just like people, some T cells have excellent memories. These subtypes known as memory T cells may explain why some immunotherapies are more effective than others and potentially lead to researchers designing more effective studies using combination checkpoint blockade treatments, according to experts at The University of Texas MD Anderson Cancer Center.

The study demonstrated that anti-CTLA-4 and anti- PD-1 immunotherapies together appear to enhance response rates and generate formation of memory T cells in mice vaccinated with melanoma cells. The combination could explain why relapse occurs in some patients with therapies targeting CTLA-4 and PD-1 checkpoints, which evade the body's immune system.

Findings from the study conducted in the lab of checkpoint blockade pioneer, James Allison, Ph.D., chair of Immunology, were presented today at the American Association for Cancer Research Annual Meeting 2018 in Chicago.

"We are learning more about the differences between anti-CTLA-4 and anti-PD-1 therapies," said Stephen Mok, Ph.D., postdoctoral fellow of Immunology, who presented findings. "We know that while anti-PD-1 therapy has a greater response rate than anti-CTLA-4, one issue is the durability of the responses."

Patients who receive anti-PD-1 have an average response rate of 30 percent but approximately 25 percent of the patients experience tumor relapse within two years after treatment has stopped. Patients treated with anti-CTLA-4 have a response rate of 11 percent with 22 percent of patients surviving at least 10 years.

The team took a closer look at memory T cells, which in previous bacteria and virus studies have suggested anti-CTLA-4 increases memory T cell levels. Conversely, anti-PD-1 tends to reduce their formation. Memory T cells are immune cells that previously have encountered cancer and gained the ability to recognize cancer antigens and reproduce more quickly, resulting in a faster and stronger defense. The investigators vaccinated mice with irradiated and treated them with either anti-CTLA-4 or anti-PD-1 to see if there were differences in memory T cell formation.

"Although both anti-CTLA-4 and anti-PD-1 improved tumor rejection, mice treated with anti-CTLA-4 exhibited superior tumor control, suggesting the memory T-cell response by this agent is more durable," said Allison. "In order to augment the durability of anti-PD-1 treatment, it was combined with anti-CTLA-4. What we found was that the combined treatment group had a better memory anti-tumor response compared with anti-PD-1 alone."

The team reported that collectively their findings facilitate the design of combination immunotherapy treatments that enhance both rates and generation of memory T to prevent relapse.

"Understanding how checkpoint blockade therapies affect T-cell development opens up the possibilities for refining current combination immunotherapy treatments and improving patient outcomes," said Mok.

Colm Duffy, a graduate research assistant in the Graduate School of Biomedical Sciences, Immunology, also participated in the study. Mok is funded by the Cancer Research Institute Irvington Postdoctoral Fellowship (16073450).

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

Related Stories

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 ...

Concurrent treatment with OX40- and PD1-targeted cancer immunotherapies may be detrimental

August 28, 2017
Concurrent administration of the T-cell stimulating anti-OX40 antibody and the immune checkpoint inhibitor anti-PD1 antibody attenuated the effect of anti-OX40 and resulted in poor treatment outcomes in mice.

A combination of cancer immunotherapies could save more lives

March 27, 2018
The pre-clinical study, published in Clinical Cancer Research, by Dr Sarah Buchan and colleagues, combined antibodies targeting PD-1/PD-L1, a type of immunotherapy known as checkpoint blockade that overcomes the resistance ...

Drug combination overcomes barrier to effective melanoma immunotherapy

April 12, 2018
Immunotherapies are treatments that stimulate a patient's immune cells to attack tumors. They can be very effective in melanoma—a common and aggressive form of skin tumor—but nonetheless fail in the majority of patients. ...

T cell repertoire changes predictive of anti-CTLA-4 cancer immunotherapy outcome revealed

May 28, 2014
Sequenta, Inc. today announced publication of a study done in collaboration with researchers from UCSF and UCLA that used the company's proprietary LymphoSIGHT immune repertoire sequencing platform to investigate the effects ...

Scientists find the key to improved cancer immunotherapy

July 18, 2017
Researchers at the Centro Nacional de Investigaciones Cardiovasculares Carlos III (F.S.P.) have investigated how different subtypes of essential immune-response cells called CD8+ T lymphocytes cooperate to mount a stronger ...

Recommended for you

Pregnant? Eating broccoli sprouts may reduce child's chances of breast cancer later in life

August 16, 2018
Researchers at the University of Alabama at Birmingham have found that a plant-based diet is more effective in preventing breast cancer later in life for the child if the mother consumed broccoli while pregnant. The 2018 ...

Scientists discover chemical which can kill glioblastoma cells

August 15, 2018
Aggressive brain tumour cells taken from patients self-destructed after being exposed to a chemical in laboratory tests, researchers have shown.

Three scientists share $500,000 prize for work on cancer therapy

August 15, 2018
Tumors once considered untreatable have disappeared and people previously given months to live are surviving for decades thanks to new therapies emerging from the work of three scientists chosen to receive a $500,000 medical ...

PARP inhibitor improves progression-free survival in patients with advanced breast cancers

August 15, 2018
In a randomized, Phase III trial led by researchers at The University of Texas MD Anderson Cancer Center, the PARP inhibitor talazoparib extended progression-free survival (PFS) and improved quality-of-life measures over ...

New clues into how 'trash bag of the cell' traps and seals off waste

August 15, 2018
The mechanics behind how an important process within the cell traps material before recycling it has puzzled scientists for years. But Penn State researchers have gained new insight into how this process seals off waste, ...

RUNX proteins act as regulators in DNA repair, study finds

August 15, 2018
A study by researchers from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore has revealed that RUNX proteins are integral to efficient DNA repair via the Fanconi Anemia (FA) ...

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.