How tumor cells evade the immune defense
Study led by the University of Bonn might help to improve modern
therapeutic approaches

Date:
August 5, 2020
Source:
University of Bonn
Summary:
Scientists are increasingly trying to use the body's own immune
system to fight cancer. A new study now shows the strategies tumor
cells use to evade this attack. The method developed for this
work contributes to a better understanding of the ''arms race''
between immune defense and disease. The results could help to
improve modern therapeutic approaches.



FULL STORY ========================================================================== Scientists are increasingly trying to use the body's own immune system
to fight cancer. A new study by the University of Bonn and research institutions in Australia and Switzerland now shows the strategies
tumor cells use to evade this attack. The method developed for this
work contributes to a better understanding of the "arms race" between
immune defense and disease. The results could help to improve modern therapeutic approaches. They have been published in the journal Immunity.


========================================================================== Cancer cells differ from healthy body cells -- in their appearance,
their behavior and the genes that are active in them. Often this does
not go unnoticed: The immune system registers that something is wrong and dispatches its troops to fight the tumor. However, this response is often
too weak to keep the cancer in check in the long term or even destroy it.

Researchers have therefore been trying for many years to strengthen the
immune system's defensive reaction. They do this in a similar way to
a policeman who puts his dog on the trail of an escaped criminal. In
this case, the role of the sniffer dog is taken over by the cytotoxic
T cells: They can detect and kill sick or defective cells. Each T cell
is directed against a specific characteristic, also called antigen. For
cancer therapy, the researchers are therefore looking for T cells in
patients that detect tumor antigens. They can then for instance multiply
these and inject them back into the patient. In this way they strengthen
the patient's immune response against the cancer.

However, many tumors have unfortunately developed strategies that enable
them to evade the immune system. "In our study, we investigated what
these strategies look like and what this depends on," explains Dr. Maike
Effern from the Institute of Experimental Oncology at the University
Hospital Bonn. "We focused on skin cancer, namely melanoma cells."
Melanomas differ from healthy cells in several ways. For example, a
whole range of different genes are active in them. Each of these is a
potential antigen for T cells. But which is particularly suitable for triggering a strong and lasting immune response? To answer this question,
the researchers invented a clever method in their experimental model:
They attached a kind of label to various genes that are active in the development of melanoma cells and used them to produce antigens. They then released a group of T cells against the tumor cells, which recognized
exactly this molecular label as a disease marker. The researchers then
used this strategy to investigate how the cancer cells react to being
pursued by the immune system. Depending on the gene tagged with such a
label, they found significant differences.

Cancer cells hide from the immune system "When the T cells were directed against genes responsible for melanoma-typical characteristics, we
observed that the cancer cells changed their appearance and suppressed
these genes over time," explains Effern's colleague Dr. Nicole Glodde. "So
this is how they hide from the immune system." In contrast, another gene investigated in the study is essential for the tumor's survival. This
makes it not so easy to downregulate and thus hide. "In our view, this
gene therefore has the potential to induce a very effective T cell
response," Effern emphasizes. "Our work potentially clears the way to
more effective immune therapies," hopes Prof. Dr. Michael Ho"lzel, head
of the Institute of Experimental Oncology at the University Hospital Bonn
and member of the Cluster of Excellence ImmunoSensation at the University
of Bonn. "The method we have developed also makes it possible to better understand the processes by which cancer cells slip under the radar of
the immune system."

========================================================================== Story Source: Materials provided by University_of_Bonn. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Maike Effern, Nicole Glodde, Matthias Braun, Jana Liebing, Helena N.

Boll, Michelle Yong, Emma Bawden, Daniel Hinze, Debby van den
Boorn- Konijnenberg, Mila Daoud, Pia Aymans, Jennifer Landsberg,
Mark J. Smyth, Lukas Flatz, Thomas Tu"ting, Tobias Bald, Thomas
Gebhardt, Michael Ho"lzel. Adoptive T Cell Therapy Targeting
Different Gene Products Reveals Diverse and Context-Dependent
Immune Evasion in Melanoma.

Immunity, 2020; DOI: 10.1016/j.immuni.2020.07.007 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200805102038.htm

--- up 3 weeks, 1 hour, 55 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1337:3/111)