A team of researchers has discovered that chemoresistant lung cancer cells suppress immune functions and strengthen resistance to chemotherapy by producing interleukin-34 (IL-34)—a type of cytokine.
Chemotherapy is one of the most important treatments for many cancer patients. In recent years, chemotherapies that target the immune system have been developed, resulting in remarkable advances in cancer treatments. However, the ability of tumor cells to escape immune destruction and acquire resistance to chemotherapy remain major obstacles to effective cancer therapy.
Expression of IL-34 (brown) in human primary lung adenocarcinoma tissue. IL-34 expression correlated with poor prognosis in cancer patients and was found to enhance local immunosuppression by tumor-associated macrophages, and also provides cancer cells with a critical survival signal to overcome chemotherapeutic conditions. (Baghdadi M. et. al., Sep 30, 2016, Cancer Research)
It is known that immunosuppressive macrophages accumulate at tumor sites where the tumor cells have become resistant to chemotherapy. Assistant Professor Muhammad Baghdadi, Lecturer Haruka Wada and Professor Ken-ichiro Seino of the Division of Immunobiology at Hokkaido University’s Institute for Genetic Medicine, conducted research with collaborators based on a theory that chemoresistant tumor cells produce an unidentified substance that increases tumor-associated macrophages, thus enhancing their resistance to chemotherapy.
In the latest research, the team cultivated chemosensitive A549-DS, made from A549 lung cancer cells, together with the chemotherapeutic drug doxorubicin, to create doxorubicin-resistant A549-DR. The researchers examined the two cells, finding a large amount of IL-34 was produced in the A549-DR, but not in the A549-DS.
They also found that the IL-34 produced by A549-DR contributed to the production of immunosuppressive macrophages. Furthermore, their experiment showed that IL-34 enhanced the chemoresistance of A549-DR.
In experiments using mice, researchers found that A549-DR was resistant to the chemotherapeutic drug when transplanted in mice, while A549-DR with depleted IL-34 became sensitive to the same drug, suggesting that IL-34 enhanced chemoresistance in the animal body.
Furthermore, researchers discovered high levels of IL-34 in tumors removed from several lung cancer patients. They also examined the prognoses of post-operative patients—studying those with, and those without IL-34 in their tumors, finding that the former’s prognoses were poorer than the latter’s.
“Currently, there are only a few options to treat chemoresistant tumors.,” Professor Seino said. “This latest finding could make it possible to develop a new therapy, which targets IL-34, to treat chemoresistant cancer cells”.
The research was jointly conducted with Kanagawa Cancer Center, Shiga University of Medical Science, and the University of Tokyo.
Professor Ken-ichiro Seino
Division of Immunobiology, Institute for Genetic Medicine
Naoki Namba (Media Officer)
Global Relations Office
Office of International Affairs
Baghdadi M. et. al., Chemotherapy-induced IL-34 enhances immunosuppression by tumor-associated macrophages and mediates survival of chemoresistant lung cancer cells. Sep 30, 2016, Cancer Research. DOI: 10.1158/0008-5472
Hokkaido University | Research SEA
Ion treatments for cardiac arrhythmia — Non-invasive alternative to catheter-based surgery
20.01.2017 | GSI Helmholtzzentrum für Schwerionenforschung GmbH
Seeking structure with metagenome sequences
20.01.2017 | DOE/Joint Genome Institute
An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
19.01.2017 | Event News
10.01.2017 | Event News
09.01.2017 | Event News
20.01.2017 | Awards Funding
20.01.2017 | Materials Sciences
20.01.2017 | Life Sciences