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

Cancer cells put the brakes on immune system

No. 41 | 28/07/2017 | by Koh

In order for cancer cells to successfully spread and multiply, they must find a way to avoid the body's own immune system. Scientists at the German Cancer Research Center (DKFZ) have published an explanation for how this occurs with chronic lymphatic leukemia (CLL). The degenerated cells cause an inflammatory reaction and influence other blood cells with it so much, that the immune system is suppressed. They send out messages via exosomes, little bubbles, which the cells transmit to their surroundings. The discovery by the DKFZ scientists paves the way for new therapy approaches.

Macrophage after treatment with green colored exosomes (blue nucleus, red: cytoskeleton)

Tumor cells influence their environment in order to avoid an immune response and to facilitate favorable conditions for growth. It has been known for a long time that solid tumors, those which grow as solid tissue inside an organ, manipulate macrophages, the 'big eater' cells of the immune system, for their own purposes. "Recently, we have seen more and more evidence that something similar must be happening in leukemia", says Martina Seiffert of the German Cancer Research Center in Heidelberg. So leukemia cells, acquired by the patient through CLL, could only survive in a culture cell if it also contains macrophages or monocytes, the precursors of the 'big eaters'. They serve as a form of nourishment for cancer cells.

Seiffert's team has now discovered how the interplay between leukemia cells and monocytes becomes a catalyst for cancer development. "We know that the so-called PD-L1 receptor occurs more frequently on the surface of these nourishing cells, and suppresses the immune response", says Seiffert. "What we have here is a so-called immune checkpoint, which prevents excessive immune responses." In this case, however, the immune response is suppressed so much that the cancer cells can multiply unopposed. In addition, the monocytes send out semiochemicals, which belong to the inflammation response of the immune system and support the growth and multiplication of the cancer cells.

The decisive question has been, how the leukemia cells can manipulate the monocytes in their environment. The scientists initially presumed that exosomes might play a role – little bubbles which are transmitted from cells to their surrounding environment. They help cells communicate with each other and influence each other's behavior. The blood plasma of CLL patients does in fact exhibit a larger number of exosomes, which are sent out by leukemia cells. The analysis of these exosomes has shown that among other things they contain Y RNA. This is a class of short RNA molecules about whose function not much is known.

In order to evaluate the effect of the Y RNA, the scientists treated monocytes and macrophages of humans and mice with suspect exosomes, as well as purified Y RNA from those exosomes, in a culture dish. In both cases the cells changed similarly to how they would in CLL patients. "They carry more PD-L1 receptors to their surface and emit semiochemicals which accelerate the immune response and create favorable growth conditions for leukemia cells", explained Franziska Haderk, principal author of the publication.

Another discovery: The Y RNA message of the so-called Toll-Like receptors 7 and 8 (TLR7/8) is found in the monocytes. These serve to register foreign RNA, such as from pathogens, and to activate the immune response. At the same time, the activation of the Toll-Like receptors also strengthens the immune inhibitor PD-L1. "This creates an environment which supports the survival of the cancer cells and recruits cells of the immune system, but at the same time stops an effective response of the immune cells via the PD-L1", says Haderk.

With this, the DKFZ researchers have at identified multiple new therapy approaches. In addition to a suppression of the PD-L1 receptor, it is conceivable to inhibit the recognition of the Y RNA message. "This could perhaps succeed by adding TLR inhibitors such as Chloroquin, a medication which is used for Malaria and rheumatic inflammation", explained Seiffert. In experiments with mice given CLL cells, the agent was able to markedly suppress the reproduction of cancer cells. "That makes Chloroquin an interesting candidate for a combination therapy along with other agents", said Seiffert.

Franziska Haderk, Ralph Schulz, Murat Iskar, Laura Llaó Cid, Thomas Worst, Karolin V.Willmund, Angela Schulz, Uwe Warnken, Jana Seiler, Axel Benner, Michelle Nessling,Thorsten Zenz, Maria Göbel, Jan Dürig, Sven Diederichs, Jérôme Paggetti, EtienneMoussay, Stephan Stilgenbauer, Marc Zapatka, Peter Lichter und Martina Seiffert: Tumor-derived exosomes modulate PD-L1 expression in monocytes. Science Immunology 2017, DOI: 10.1126/sciimmunol.aah5509

An image for press releases is available at:

BU: Macrophage after treatment with green colored exosomes (blue nucleus, red: cytoskeleton)

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