Attack or peacekeeping? Immune cells answer this
question countless times a day. If they regularly missed the mark, it would
have serious consequences for human health. The regulatory T cells discovered
by Shimon Sakaguchi help the immune system to distinguish between friend and
foe and are instrumental for achieving self-tolerance. Strengthening or
weakening this peacekeeping force gives the immune system a kick or a damper.
Both strategies can be harnessed to develop new treatments for human diseases.
am MAIN. Tomorrow, Shimon Sakaguchi, professor of
Experimental Immunology at Osaka University (Japan) will receive the 2020 Paul
Ehrlich and Ludwig Darmstaedter Prize for his pioneering discoveries of
regulatory T cells and their role in self-tolerance. These cells have the
potential to become the new heroes of medicine. They keep the immune system in
balance and ensure that it doesn´t run amok or becomes inattentive.
"Without regulatory T cells, the immune system would not be able to
correct errors in distinguishing between friend and foe with the necessary
precision," explained the Scientific Council of the Paul Ehrlich
Foundation when presenting the award. "The immune system needs such
regulatory control, because overreaction leads to autoimmune diseases such as
rheumatoid arthritis and type 1 diabetes, whereas reduced activity gives cancer
cells the opportunity to evade immune attack and eventually establish
metastases. Therefore, Sakaguchi's discovery offers great potential for the
development of new treatments."
Early on in his studies,
Sakaguchi was convinced that an immunological peacekeeping force must exist in
order to establish immune homeostasis. The difficulty he faced was that there
was no molecular marker that would allow him to identify and isolate these
cells. Therefore, Sakaguchi set out to search for such a telltale feature.
After many years of painstaking work, he demonstrated that the surface protein
CD25 is a reliable marker for these cells. "The discovery of CD25 was a
watershed in immunological research. It proved the existence of regulatory
T-cells and pointed a way forward to isolate and characterize them in greater
detail," said Professor Thomas Boehm, Director at the Max Planck Institute
of Immunobiology and Epigenetics in Freiburg, and Chairman of the Scientific
Council. "This seminal discovery has given the field of immune regulation
an enormous boost. Suddenly, many scientists became interested in the biology
and use of regulatory T cells."
Subsequently, Sakaguchi was able to show that Foxp3
is the central on/off switch of regulatory T cells, a finding that was quickly
confirmed by others. This discovery established an unexpected connection
between regulatory T cells and a rare congenital syndrome known as IPEX, which
had been shown to be due to the lack of Foxp3. IPEX patients develop severe
autoimmune diseases shortly after birth, often leading to early death. Thus,
the medical relevance of Sakaguchi´s earlier discovery of regulatory T cells
became obvious: patients with IPEX syndrome suffered from lack of an
immunological peacekeeping force.
Because of their fundamental importance for the
immune system, the manipulation of regulatory T cells offers new forms of
treatment for a wide range of conditions. In the case of autoimmune diseases
such as rheumatoid arthritis, type 1 diabetes and multiple sclerosis, their
activity must be strengthened so that they can take more decisive action
against inappropriate attacks on the body's own tissue. In cancer, the activity
of regulatory T cells needs to be attenuated. Although they no longer adhere to
their normal cellular program, cancer cells are often not considered foreign by
the immune system. Hence, the protection of tumor cells by regulatory T cells
is unfortunate, as this prevents them from being eliminated. Therefore, to
eliminate the tumor´s camouflage, regulatory T cells, which are
disproportionately abundant in tumors, must be either reduced in number or
their activity diminished to allow an efficient attack on the tumor.
Attenuation of regulatory T cell activity, however,
needs to be very precisely controlled, both in space and in time, for they are
needed elsewhere in the body to maintain immune homeostasis. "The
challenge is to manipulate regulatory T cells only at the site of the tumor,"
Thomas Boehm explains. "In one approach, Sakaguchi is attempting to
convert tumor resident regulatory T cells into conventional T-cells, which then
switch sides and participate in attack. If this strategy is successful, an
essential component of the body´s peacekeeping force will be converted into an
aggressor directed at the malignant tissue ".
At present, various strategies
for the treatment of autoimmune diseases and cancer based on the manipulation
of regulatory T cells are being evaluated, although these approaches are still
in an early phase of clinical development. As with many groundbreaking ideas,
therapeutic application requires a long period of painstaking work before they
can be offered to patients.
biography of Professor Shimon Sakaguchi
Professor Shimon Sakaguchi, M.D.
(69) is a medical doctor. He studied medicine at Kyoto University in Japan,
then moved to Johns Hopkins University in Baltimore as a post-doctoral fellow
and then to Stanford University in California. In 1989 he became an
"Assistant Professor" at the Scripps Research Institute in La Jolla.
In 1991, Sakaguchi returned to Japan and worked at the Tokyo Metropolitan
Institute of Gerontology and later at the Institute for Frontier Medical
Sciences at Kyoto University, where he was temporarily director. Since 2011, he
has been working at Osaka University. In 2012 he became a Foreign Member of the
American National Academy of Sciences and in 2017 the Japanese government
appointed him "Person of Cultural Merit". Sakaguchi has received many
awards, including the William B. Coley Award from the Cancer Research
Institute, the Keio Medical Science Prize, the Canada Gairdner International
Award and the Crafoord Prize. Last year he was awarded the "German
Immunology Prize 2019".
The Paul Ehrlich and Ludwig
The Paul Ehrlich and Ludwig Darmstaedter Prize
is traditionally awarded on Paul Ehrlich's birthday, March 14, in the
Paulskirche, Frankfurt. It honors scientists who have made significant
contributions in Paul Ehrlich's field of research, in particular immunology,
cancer research, microbiology, and chemotherapy. The Prize, which has been
awarded since 1952, is financed by the German Federal Ministry of Health, the
German association of research-based pharmaceutical company vfa e.V. and
specially earmarked donations from the following companies, foundations and
organizations: Christa Verhein Stiftung, Else Kröner-Fresenius-Stiftung,
Sanofi-Aventis Deutschland GmbH, C.H. Boehringer Sohn AG & Co. KG, Biotest AG, Hans und Wolfgang
Schleussner-Stiftung, Fresenius SE & Co. KGaA, F. Hoffmann-LaRoche Ltd.,
Grünenthal Group, Janssen-Cilag GmbH, Merck KGaA, Bayer AG, Holtzbrinck
Publishing Group, AbbVie Deutschland GmbH & Co. KG, die
Baden-Württembergische Bank, B. Metzler seel. Sohn & Co. and Goethe-Universität. The prizewinner is selected by the Scientific Council
of the Paul Ehrlich Foundation.
Paul Ehrlich Foundation
Paul Ehrlich Foundation is a legally dependent foundation which is managed in a
fiduciary capacity by the Association of Friends and Sponsors of the Goethe
University, Frankfurt. The Honorary Chairman of the Foundation, which was
established by Hedwig Ehrlich in 1929, is Professor Dr. Katja Becker, president
of the German Research Foundation, who also appoints the elected members of the
Scientific Council and the Board of Trustees. The Chairman of the Scientific
Council is Professor Thomas Boehm, Managing Director at the Max Planck
Institute of Immunobiology and Epigenetics in Freiburg, the Chair of the Board
of Trustees is Professor Dr. Jochen Maas, Head of Research and Development and
Member of the Management Board, Sanofi-Aventis Deutschland GmbH. Professor
Wilhelm Bender, in his function as Chair of the Association of Friends and Sponsors of the
Goethe University, is Member of the Scientific Council. The President of the Goethe University is at the same time a member of
the Board of Trustees.
You can obtain selected publications, the list of publications and a
photograph of the laureate from Dr. Hildegard Kaulen, phone: +49 (0)6122/52718,
email: email@example.com and at www.paul-ehrlich-stiftung.de