2020 Lautenberg Center Progress Report

COMPLICATIONS ASSOCIATED
WITH CHRONIC INFLAMMATION:
THE ROLE OF MYELOID DERIVED
SUPPRESSOR CELLS (MDSCS).
MDSCs as multi-tasking sensors and
orchestrators of divers clinical outcomes
Michal Baniyash
Lay language summary
In pathologies characterized by chronic inflammation altered formation of various blood cells
originating in the bone marrow is evident, in association with the accumulation of myeloid
derived suppressor cells (MDSCs). MDSCs are heterogenous cells featured by highly immune
suppressive activities. These cells are found in sites of inflammation as in various tumors, in
inflammatory organs as the intestine, during inflammatory bowel disease (IBD) and the
stomach, during Helicobacter Pillory infection. In most cases, when the disease is severe,
inflammation is also evident in the periphery. MDSCs have the capacity to impair immune
functions of different lymphocytes required for the execution of an optimal immune response
and exacerbate the body’s inflammatory state. These ensue in a variety of complications as
tissue damage, susceptibility to infections and high risk to develop cancer. In the course of
our studies, we discovered that MDSCs are diverse and plastic; when reaching a new
environment, which exhibits a unique array of pro-inflammatory mediators/growth factors, they
can sense and adapt to the altered micro-environment by virtue of acquiring different features
that involve changing their cell fate, surface molecules, metabolism and intracellular as well
as secreted compounds. For example, we discovered that during chronic inflammation a
subpopulation of MDSCs localized in the bone marrow can differentiate to highly active
osteoclasts, which are cells that resorb the bone, and lead to inflammatory bone loss and
osteoporosis. We also discovered that MDSCs can communicate with bacteria in the damaged
intestine during IBD. This results in the enhancement of MDSC suppressive and inflammatory
functions, thus supporting the process of colon cancer development. As MDSCs have harmful
immune suppressive effects under chronic inflammatory conditions, they are the major
obstacles for the success of various anti-cancer treatments based on the immune system.
Therefore, major efforts are now gathered in using MDSCs as: 1) Biomarkers for the
evaluation of chronic inflammation-induced complications, 2) As predictors of success rates
of immune-based therapies, and 3) As targets for treatments aimed at combating them
towards achieving recuperated immune responses and thus, improving therapies in various
pathologies characterized by chronic inflammation including cancer.
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