First extensive immune profile of sarcomas shows some likely susceptible to immunotherapy

May 2, 2017, Fred Hutchinson Cancer Research Center

Sarcomas—cancers of the connective tissues like muscles, joints, fat and bone—come in dozens of subtypes. Clinical trial results have been mixed when treating these diverse tumors with immunotherapy, a targeted therapeutic strategy that has success in other cancers.

But now a study to be published May 2 in the journal Cancer suggests how both existing and emerging immunotherapy treatments could be successful for sarcomas.

Two sarcoma subtypes—leiomyosarcoma and pleomorphic—showed biological characteristics suggesting they are susceptible to an existing immunotherapy approach known as checkpoint inhibitors. This treatment works by blocking a protein that keeps from attacking cancerous cells.

"Checkpoint inhibitors have transformed the standard of care for melanoma and lung cancer, but it's been tough to make headway in developing immunotherapy strategies for sarcomas," said Dr. Seth Pollack, a clinical researcher at Fred Hutchinson Cancer Research Center and the study's senior author. "Before this study, we had a feeling based on preliminary data that some of the sarcomas would behave very differently based on the , and these findings suggest that we're on the right track."

Sarcomas comprise more than 70 different cancers that can originate anywhere in the body and are usually named after the tissue from which they arise.

In the most extensive sarcoma immune profiling to date, Pollack and his colleagues examined tumor samples from 81 patients with types of sarcoma that comprise 75 percent of the disease: leiomyosarcoma, pleomorphic sarcoma, synovial sarcoma and liposarcoma. The samples came from patients who had agreed to allow researchers to study their tumors for developing new therapies.

The researchers aimed to identify patterns of immune response in these sarcomas to identify promising targets for therapies. They measured:

  • expression of 760 genes, mainly related to immune function;
  • levels of proteins called PD-1 and PD-L1 on T cells that tumors use as an off switch to keep the immune system from attacking cancer cells;
  • the proportion of T cells in tumors, which indicates how successful the immune system is at attacking cancer on its own; and
  • T-cell receptor clonality, which indicates the precision of the T- cell response.

Leiomyosarcoma and pleomorphic sarcomas were the two subtypes that had a greater immune response by nearly all of the measures in the study, which means that they're more visible to the immune system.

"To me, these findings say that there are certain sarcoma subtypes that really lend themselves to the development of checkpoint inhibitor-based strategies," Pollack said. Checkpoint inhibitors are immunotherapies that remove the PD-1 "off switch" and essentially allow the immune system to attack cancer more aggressively.

Meanwhile, synovial sarcoma and liposarcoma had low levels of the immune response markers, suggesting that other immunotherapeutic strategies, such as adoptive T-cell therapies or vaccines, would work better.

"It's too early to change how doctors will treat patients, but these findings are influencing the design of clinical trials in sarcoma," Pollack said.

Other studies have suggested there may be unexpected challenges treating leiomyosarcoma with these therapies and that those patients may benefit from combination approaches with other treatments.

"Our results show that even though other studies have been unclear about whether checkpoint inhibitors work for leiomyosarcoma, that there's still a way to make them work for this subtype and that we need to keep working on it," Pollack said.

Pollack is conducting ongoing clinical trials combining chemotherapies and checkpoint inhibitors:

Ultimately, he hopes to expand treatment options for patients with advanced sarcoma who have an estimated survival of 12 to 18 months.

Sarcomas comprise about 1 percent of all cancers; about 20,000 people a year are diagnosed each year in the United States with one of its many subtypes. Though sarcomas are often called "rare," Pollack said that's a misnomer.

"Indeed there are many rare subtypes of , but added together they have similar incidence compared with other cancers that get more attention such as esophageal , Hodgkin lymphoma and acute myeloid leukemia," he said.

Explore further: Deploying an ancient defense to kill cancer

More information: Seth M. Pollack et al, T-cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death-ligand 1 expression in patients with soft tissue sarcomas, Cancer (2017). DOI: 10.1002/cncr.30726

Related Stories

Deploying an ancient defense to kill cancer

April 3, 2017
A recent small trial in 15 cancer patients with advanced soft-tissue sarcomas aimed to find out whether an experimental drug based on a certain bacterial molecule could trigger an immune response to fight cancer.

PI3K/mTOR inhibitors may be effective against some uterine sarcomas

February 23, 2017
The protein P-S6S240 may serve as an indicator of poor prognosis for patients with a hard-to-treat type of uterine sarcoma called leiomyosarcoma, and preclinical data suggest that patients whose tumors have this protein may ...

Immunotherapy effective against some types of sarcoma

June 6, 2016
An existing cancer immunotherapy drug reduces tumor size in some types of rare connective tissue cancers, called sarcomas, report researchers at the University of Pittsburgh Cancer Institute (UPCI). Additional analyses of ...

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 ...

CTCA at Western launches immunotherapy clinical trial aimed at soft-tissue cancers

September 18, 2015
Cancer Treatment Centers of America (CTCA) at Western Regional Medical Center (Western) in Goodyear, Arizona, has begun Phase II of another arm of its multi-arm clinical trial that combines immunotherapy with chemotherapy.

PET radiotracer design for monitoring targeted immunotherapy

April 7, 2017
In an article published in the April issue of The Journal of Nuclear Medicine, researchers at Stanford University in California provide a template for assessing new positron emission tomography (PET) radiotracers that can ...

Recommended for you

Obesity both feeds tumors and helps immunotherapy kill cancer

November 12, 2018
A groundbreaking new study by UC Davis researchers has uncovered why obesity both fuels cancer growth and allows blockbuster new immunotherapies to work better against those same tumors.

Spread of deadly eye cancer halted in cells and animals

November 12, 2018
By comparing genetic sequences in the eye tumors of children whose cancers spread with tumors that didn't spread, Johns Hopkins Medicine researchers report new evidence that a domino effect in cells is responsible for the ...

Cancer stem cells get energy from protein, and it's proving to be their Achilles' heel

November 12, 2018
Think of energy metabolism like a party popper: Ripping something apart releases a bang. Most of your cells rip apart sugar to release the "bang" of energy. Sometimes they rip apart fats, and in a pinch, cells can even metabolize ...

Scientists shine new light on link between obesity and cancer

November 12, 2018
Scientists have made a major discovery that shines a new, explanatory light on the link between obesity and cancer. Their research confirms why the body's immune surveillance systems—led by cancer-fighting Natural Killer ...

Two-pronged device enables maverick immune cells to identify and kill cancers

November 12, 2018
Immune cells called Gamma Delta T cells can act independently to identify and kill cancer cells, defying the conventional view of the immune system, reveals new research from the Francis Crick Institute and King's College ...

Research brings personalized medicine to treat leukemia one step closer

November 12, 2018
Scientists at the University of Birmingham have revealed the roles that different types of gene mutations play in causing blood cancers in a study that was the culmination of a decade's research.

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.