The immune system's double agents
Discovery may help the war against cancer

Date:
October 4, 2021
Source:
Tel-Aviv University
Summary:
A new study examined the development of a glioblastoma cancerous
tumor in animal models with a normal immune system, in order to
best simulate the development of the tumor in humans.



FULL STORY ==========================================================================
A new Tel Aviv University study examined for the first time the
development of a glioblastoma cancerous tumor in animal models with
a normal immune system, in order to best simulate the development of
the tumor in humans. The findings of the study showed that there are
immune system cells that, despite the fact that their primary function
is to attack and kill the cancer cells, actually act as "double agents"
that increase and intensify the aggressiveness and threat of the tumor.


==========================================================================
The study was led by Dr. Dinorah Friedmann-Morvinski of the George
S. Wise Faculty of Life Sciences and Sagol School of Neuroscience, and
her PhD student and Prerna Magod Also participating in the study were
Dr. Liat Rousso-Noori and Ignacio Mastandrea, also from the Faculty of
Life Sciences, as well as other researchers from the Sackler Faculty of Medicine at Tel Aviv University and the Weizmann Institute of Science. The study was published in the journal Cell Reports.

Glioblastoma is the most common type of brain cancer, and one of
the most violent and deadly cancers in humans; the average life
expectancy of glioblastoma patients is 12 to 15 months from the moment
of detection. The researchers explain that usually, the scientific
monitoring of the development of the cancerous tumor in animal models
is carried out without an active immune system, in order to enable the absorption and growth of cancer cells in the body. The disadvantage of
this commonly-used model lies in the fact that the immune system either
does not exist or does not function properly, which prevents researchers
from monitoring the interaction between it and the tumor cells.

The study, which was conducted in Dr. Friedmann-Morvinski's laboratory,
used a model that examined the development of cancer cells in animal
models with functioning immune systems. This allowed the cancer to
grow gradually, to the point of the development of a massive tumor,
which enabled the close monitoring of its development, and throughout
the process, of the interaction between the cancer cells and different
immune system cells.

In the study, the researchers found that cells called neutrophils play a critical role in interacting with the cancerous growth. Neutrophils are
immune system cells that originate in the bone marrow, and whose purpose
is to "swallow" or kill bacteria and fungi and fight the infections
caused by them.

"Neutrophils are the front-line soldiers of the immune system," says Dr.

Friedmann-Morvinski. "When a tumor begins to develop, the neutrophils
are among the first to mobilize and attack it in order to eliminate it."
The researchers also found that the neutrophils remain in close proximity
to the tumor throughout its development, and are continuously and
consistently recruited from the bone marrow. The surprising thing that
was discovered during this study is that the neutrophils "change sides:" Whereas at first, with the onset of the initial tumor, the neutrophils
fight it, over time the neutrophils recruited to the cancerous area
begin to support its development.

Dr. Friedmann-Morvinski: "We learned that the neutrophils actually change
their role. They are mobilized by the tumor itself, and from being anti-cancerous, become pro-cancerous; as a result, they aggravate the
damage that the tumor itself creates." Moreover, the researchers found
that the process by which the neutrophils change their properties can
take place remotely, even before they progress towards the tumor itself.

"The study showed that the change in the properties of neutrophils
takes place in the bone marrow itself -- where there is no tumor at
all: the cancerous tumor is located only in the brain, and from there
it succeeds in changing the properties of the cells it recruits," adds
Dr. Friedmann-Morvinski. "The new findings of this study may also shed
light on immunotherapeutic therapies, which have been gaining a lot
of momentum in recent years. In one type of immunotherapy treatment,
T cells are removed from the patient's body, processed, and returned
to the body with increased healing abilities. One of the major problems
today is that even these cells that have been sent to heal are suppressed
and their actions stifled. If we know how to change the interaction
between neutrophils and T cells so that they are not suppressed, this
will have implications for the effectiveness of immunotherapy." It is
not inconceivable that these revelations are the first step towards
deciphering the mechanism of interaction between the immune system and
violent cancerous tumors that, as mentioned, claim the lives of so many.

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


========================================================================== Journal Reference:
1. Prerna Magod, Ignacio Mastandrea, Liat Rousso-Noori, Lilach
Agemy, Guy
Shapira, Noam Shomron, Dinorah Friedmann-Morvinski. Exploring the
longitudinal glioma microenvironment landscape uncovers reprogrammed
pro- tumorigenic neutrophils in the bone marrow. Cell Reports,
2021; 36 (5): 109480 DOI: 10.1016/j.celrep.2021.109480 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211004104220.htm

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