Given how effectively the immune system can eliminate foreign threats such bacteria and viruses, hopes are high for the development of strategies that might turn these same defense mechanisms against cancerous targets.
However, attempts to train the immune system to recognize malignancies via the intravenous injection of vaccines that present tumor-derived antigens have fallen short.
According to Kenichi Asano, a researcher with Masato Tanaka’s group at the RIKEN Center for Allergy and Immunology in Yokohama, this is the result of ‘tolerance’ mechanisms that protect against autoimmune disease. “Billions of cells die every day, and cell corpses must be removed swiftly from our body in order not to induce detrimental effects,” he says. In this scenario, macrophage cells in the spleen clean house by devouring such debris in a process known as phagocytosis, thereby preventing dead cells from triggering an inflammatory response.
Tumor cells delivered into the lymphatic system via subcutaneous injection, however, can successfully elicit a strong immune response, and new research from Asano and colleagues explains why this is the case. In order to rouse an effective reaction, phagocytic cells must present recognizable chunks of those dead cells to tumor-killing cytotoxic T lymphocytes (CTLs). The researchers identified a very specific subset of macrophages within the lymph nodes that perform this task.
Intriguingly, these cells, which are distinguishable by their expression of the cell-surface protein CD169, are non-migratory and reside stably within the sinuses of the lymph node, awaiting their prey like spiders in a web. Dead cancer cells delivered to these sinuses via the lymphatic system are rapidly digested by the macrophages (Fig. 1), which in turn cross-present the resulting antigens to CTLs. By selectively killing off these macrophages with diphtheria toxin, the researchers were able to essentially disable the immune response. “Without CD169 macrophages, tumor-directed T cells were no longer activated—that means these cells dominate anti-tumor immunity after tumor cell death,” says Asano.
These findings help explain why the dead cells that slough off of tumors into the lymphatic system during radiation or chemotherapy are sometimes sufficient to provoke an immune response, and could provide the foundation for far more effective cancer immunotherapy strategies. “I believe it is very promising to mount anti-tumor immunity in patients with solid tumors by delivering tumor antigens specifically to CD169 macrophages,” says Asano. “It's my dream to invent artificial materials that possess the characteristics of dead cells and are safe for administration to patients.”
The corresponding author for this highlight is based at the Laboratory for Innate Cellular Immunity, RIKEN Research Center for Allergy and Immunology
 Asano, K., Nabeyama, A., Miyake, Y., Qiu, C.-H., Kurita, A., Tomura, M., Kanagawa, O., Fujii, S.-I. & Tanaka, M. CD169-positive macrophages dominate antitumor immunity by crosspresenting dead cell-associated antigens. Immunity 34, 85–95 (2011).
gro-pr | Research asia research news
Bare bones: Making bones transparent
27.04.2017 | California Institute of Technology
Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel
More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.
Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...
Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.
"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...
The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.
Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...
The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...
Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.
Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...
20.04.2017 | Event News
18.04.2017 | Event News
03.04.2017 | Event News
27.04.2017 | Life Sciences
27.04.2017 | Physics and Astronomy
27.04.2017 | Earth Sciences