Cookie Settings

We use cookies to optimize our website. These include cookies that are necessary for the operation of the site, as well as those that are only used for anonymous statistic. You can decide for yourself which categories you want to allow. Further information can be found in our data privacy protection .


These cookies are necessary to run the core functionalities of this website and cannot be disabled.

Name Webedition CMS
Purpose This cookie is required by the CMS (Content Management System) Webedition for the system to function correctly. Typically, this cookie is deleted when the browser is closed.
Name econda
Purpose Session cookie emos_jcsid for the web analysis software econda. This runs in the “anonymized measurement” mode. There is no personal reference. As soon as the user leaves the site, tracking is ended and all data in the browser are automatically deleted.

These cookies help us understand how visitors interact with our website by collecting and analyzing information anonymously. Depending on the tool, one or more cookies are set by the provider.

Name econda
Purpose Statistics
External media

Content from external media platforms is blocked by default. If cookies from external media are accepted, access to this content no longer requires manual consent.

Name YouTube
Purpose Show YouTube content
Name Twitter
Purpose activate Twitter Feeds

DKTK Berlin and Heidelberg: New Biomarker for cancer immunotherapy?

No. 27 | 01/08/2016 | by AM

The Ligand PD-L1 is one of the most important targets for cancer immunotherapy with checkpoint inhibitors. But not all tumors have sufficient quantities of PD-L1 ligands on their surface. Scientists from the German Cancer Consortium (DKTK) have now shown that different types of cancer possess different quantities of PD-L1-Gen copies. Genetic analysis of the PD-L1 gene may in the future help to predict which patients will benefit from checkpoint inhibitors. In the German Cancer Consortium (DKTK), the German Cancer Research Center (DKFZ) is serving as a core center that joins up with university institutes and hospitals all over Germany that are specialized in research and treatment with a focus on oncological diseases.

Different number of PD-L1 gen copies (green) in the chromosoms (blue) from bladder tumor cells (Fluorescence in-situ hybridisation).
© J. Budczies, Charité/ A. Stenzinger, Uniklinikum Heidelberg

A hundred years ago, scientists had already put forward the hypothesis that the immune system recognizes cancer cells and eliminates them. But it was only recently that a major breakthrough was achieved with so-called checkpoint inhibitors. They act on the immune system's checkpoints. In a healthy person, these checkpoints prevent an exaggerated immune response. Tumors take advantage of the fact that these checkpoints suppress the immune response against them. And this is where the checkpoint inhibitors come in: They block the signaling pathway, effectively releasing the breaks of the immune system and thus giving the body's defenses the opportunity to attack the tumor.

PD-L1 can be used in diagnostic testing

The promising target structure to treat tumors with checkpoint inhibitors is the receptor for programmed cell death 1 (PD-1) which occurs on t-cells, and its ligand PD-L1, which occurs in most tumor cells. First, drugs canceling out the tumor-related break function in the immune defense via this checkpoint are already available on the market. "PD-L1 is also an interesting biomarker for diagnostic testing to predict the patients' response to the immunotherapy", explains Jan Budczies, bioinformatician at the DKTK partner institution Charité Berlin. "Current studies however show that the interrelationships are quite complex." Therefore, not all patients with PD-L1 in the tumor tissue responded to a therapy with PD-L1 blockers. On the other hand, treatment has been shown to be successful in patients where hardly any PD-L1 protein was detected in the tumors.

Tumors of different cancer types differ in the number of PD-L1 gene copies

In collaboration with scientists at DKTK sites in Berlin, München and Heidelberg, the team around bioinformatician Jan Budczies and pathologist Albrecht Stenzinger showed that tumors from many cancer types differ in the number of PD-L1 gene copies. In the tumor genomes of 9771 patients with 22 different cancer forms, including the most common such as lung, colon and breast cancer, the scientists found that quantities of copies of the PD-L1 gene and other neighboring genes were altered. The study showed that whenever gene copies were deleted or gained, the gene activity and the amount of PD-L1 protein in the tumor were frequently effected.

This study should help to optimize diagnostic tests for the deployment of checkpoint inhibitors, and to better understand tumor biology with regard to immunotherapy and other therapeutic methods. "We were able to show that the number of PD-L1 gene copies may be altered in different types of cancer", explains Albrecht Stenzinger from the Institute of Pathology of the University Hospital Heidelberg and the National Center for Tumor Diseases (NCT). "This affects not only PD-L1 itself, but also numerous neighboring genes, some of which are already known as driver genes for tumor diseases. Most tumors with increased quantities of PD-L1 gene copies also possess more copies of the gene for the JAK2 kinase, which plays a role in blood disorders and was recently identified as a target structure in a breast cancer subtype associated with a dismal prognosis."

PD-L1 gene copy number is a potential biomarker

Gene analyses can contribute to the identification of further target structures neighboring PD-L1. "Studies of this kind are extremely complex and can only be performed by an interdisciplinary team of medical experts and basic researchers. By combining the expertise of oncologists, bioinformaticians and pathologists, the DKTK offers ideal conditions", Albrecht Stenzinger enthuses. Jan Budczies, who is responsible for the bioinformatic part of the study points out that "big data analyses are an important tool of modern medicine. But for us to translate the results quickly into benefits for patients, scientists must collaborate on an interdisciplinary basis."

The analysis of PD-L1 Gen copy and PD-L1 Gen receptors may help to identify patients that will especially benefit from an immunotherapy with checkpoint inhibitors. Two recently published studies on the Hodgkin lymphoma have shown that PD-L1 Gen copy analysis is indeed relevant for clinical practice. Both, the progression of the disease and the success of the treatment with PD-1 signaling pathway inhibitors could be predicted on the basis of copy numbers of the PD-L1 gene. Budczies and Stenzinger's work suggests that this could also be the case for various other cancer types.

Budczies, J. et. al.: Pan-Cancer Analysis of Copy Number Changes in Programmed Death-Ligand 1 (PD-L1, CD274) – Associations with Gene Expression, Mutational Load, and Survival. In: Genes, Chromosomes & Cancer (22. April 2016) DOI: 10.1002/gcc.22365

A picture for this press release is available at:

Legend: Different number of PD-L1 gen copies (green) in the chromosoms (blue) from bladder tumor cells (Fluorescence in-situ hybridisation). (©J. Budczies, Charité/ A. Stenzinger, Uniklinikum Heidelberg)

With more than 3,000 employees, the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) is Germany’s largest biomedical research institute. DKFZ scientists identify cancer risk factors, investigate how cancer progresses and develop new cancer prevention strategies. They are also developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to questions relating to cancer.

To transfer promising approaches from cancer research to the clinic and thus improve the prognosis of cancer patients, the DKFZ cooperates with excellent research institutions and university hospitals throughout Germany:

  • National Center for Tumor Diseases (NCT, 6 sites)
  • German Cancer Consortium (DKTK, 8 sites)
  • Hopp Children's Cancer Center (KiTZ) Heidelberg
  • Helmholtz Institute for Translational Oncology (HI-TRON Mainz) - A Helmholtz Institute of the DKFZ
  • DKFZ-Hector Cancer Institute at the University Medical Center Mannheim
  • National Cancer Prevention Center (jointly with German Cancer Aid)
The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.


Subscribe to our RSS-Feed.

to top
powered by webEdition CMS