Research explains limits of cancer immunotherapy drugs

October 26, 2015

Immunotherapy treatments have proven wildly successful in treating some patients with cancer. But despite this success, the majority of patients do not respond to the treatments.

A new study from the University of Michigan Comprehensive Cancer Center reveals molecular changes within the tumor that are preventing the immunotherapy drugs from killing off the .

Clinical trials with PD-L1 and PD-1 blockade suggested that tumors with a high number of inflammation-causing T cells were more responsive to the immunotherapy-based PD-L1 and PD-1 inhibitors. Tumors with low inflammation, or low T cells, were less responsive. But what controls T cells in the tumor microenvironment is poorly understood.

"We defined a molecular mechanism to explain why some tumors are inflamed and others are not - and consequently why some will be responsive to therapy and others not," says senior author Weiping Zou, M.D., Ph.D.

"If we can reprogram this epigenetic mechanism, then the therapy might work for more patients," says Zou, Charles B. de Nancrede Professor of Surgery, Immunology and Biology at the University of Michigan Medical School.

Zou's group was the first to show PD-L1 expression, regulation and functional blockade in in the human cancer microenvironment.

In this study, published in Nature, researchers studied human and mouse models of . They applied epigenetic drugs and found that the numbers of T in the tumor increased. They also saw that the epigenetic drugs synergized the anti-tumor effect of PD-L1 blockade in their models.

"We hope this could be developed into a clinical trial testing a combination of PD-L1 and PD-1 blockade with epigenetic therapy. We want to see if we can make the responders more responsive and turn the non-responders into responders," Zou says.

Explore further: Identifying protein that may predict response to PD-1 immunotherapy for melanoma

More information: Nature, "Epigenetic silencing of Th1 type chemokines shapes tumor immunity and immunotherapy," published online Oct. 26, 2015. DOI: 10.1038/nature15520

Related Stories

Identifying protein that may predict response to PD-1 immunotherapy for melanoma

September 16, 2015
Mayo Clinic researchers have identified a protein marker whose frequency may predict patient response to PD-1 blockade immunotherapy for melanoma. An abstract of their findings was presented today at the American Association ...

Study finds potential predictive biomarker for response to PD-L1 checkpoint blocker

November 26, 2014
A promising experimental immunotherapy drug works best in patients whose immune defenses initially rally to attack the cancer but then are stymied by a molecular brake that shuts down the response, according to a new study ...

Biomarker identifies melanoma patients who may respond to immunotherapy MK-3475

April 7, 2014
Among melanoma patients treated with the PD-1 inhibitor MK-3475, those whose tumors had the protein PD-L1 had better immune responses and higher survival rates, according to results presented here at the AACR Annual Meeting ...

Study points to potential new lung cancer therapy

April 20, 2015
New findings about regulation of PD-L1, a protein that allows cancer to evade the immune system, has shown therapeutic promise for several cancers, including the most common form of lung cancer.

Researchers provide rationale for use of targeted immunotherapy in sarcomatoid lung carcinomas

May 28, 2013
Sarcomatoid carcinomas of the lung include rare subtypes of poorly differentiated non–small-cell lung carcinomas of high grade and aggressive behavior. The biology of these neoplasms is poorly understood and these tumors ...

FDA approves expanded use of Opdivo in advanced lung cancer

October 12, 2015
(HealthDay)—The U.S. Food and Drug Administration has approved Opdivo (nivolumab) to treat patients with advanced non-small-cell lung cancer (NSCLC) whose disease progressed despite platinum-based chemotherapy.

Recommended for you

CAR-T immunotherapy may help blood cancer patients who don't respond to standard treatments

October 20, 2017
Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis is one of the first centers nationwide to offer a new immunotherapy that targets certain blood cancers. Newly approved ...

Researchers pinpoint causes for spike in breast cancer genetic testing

October 20, 2017
A sharp rise in the number of women seeking BRCA genetic testing to evaluate their risk of developing breast cancer was driven by multiple factors, including celebrity endorsement, according to researchers at the University ...

Study shows how nerves drive prostate cancer

October 19, 2017
In a study in today's issue of Science, researchers at Albert Einstein College of Medicine, part of Montefiore Medicine, report that certain nerves sustain prostate cancer growth by triggering a switch that causes tumor vessels ...

Gene circuit switches on inside cancer cells, triggers immune attack

October 19, 2017
Researchers at MIT have developed a synthetic gene circuit that triggers the body's immune system to attack cancers when it detects signs of the disease.

One to 10 mutations are needed to drive cancer, scientists find

October 19, 2017
For the first time, scientists have provided unbiased estimates of the number of mutations needed for cancers to develop, in a study of more than 7,500 tumours across 29 cancer types. Researchers from the Wellcome Trust Sanger ...

Researchers target undruggable cancers

October 19, 2017
A new approach to targeting key cancer-linked proteins, thought to be 'undruggable," has been discovered through an alliance between industry and academia.

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

Shapoval
not rated yet Nov 10, 2015
Father of Oncology Explains Limits of Cancer Immunotherapy Drugs. Immunotherapy is the fruition of a century-old idea. But what if cancer loves iron (cancer is a disease of iron-overloaded cells); researchers love money? Direct intratumoral injections of iron-deficiency agents/substances (ceramic needles) are needed when tumors/metastases cannot be removed with surgery (ceramic blades), the Father of Oncology explains. Unfortunately, the immune system (which is made up of special cells, proteins, tissues, and organs) cannot recognize and attack cancerous cells (iron-overloaded cells). Iron overload is not a crime, iron-overloaded cells are not our enemies, the immune system thinks. Primary tumors always develop at body sites of excessive iron deposits; such deposits can be inherited or acquired, the Father of Oncology thinks. http://www.medica...s/191369 ; https://plus.goog...SqVBV9DS ; https://www.faceb...apoval.5

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.