Citation: Chagas JR, Visniauskas B, Gomes GN and Bueno V. Evaluation of Myeloid-derived Suppressor Cells
and Components of Renin Angiotensin System in Urethane-induced Lung Cancer. J Immun Res. 2015;2(2): 1018.
J Immun Res - Volume 2 Issue 2 - 2015
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Bueno et al. © All rights are reserved
Journal of Immune Research
Open Access
Abstract
Urethane-induced lung cancer has been associated with an imbalance in the
effector/suppression immune response since interferon-gamma production is
increased along with elevated percentages of myeloid-derived suppressor cells.
The goal in cancer therapy is to prevent the immunosuppressive effects caused
by tumor and thus lead to the development of effective immune response. The
depletion of myeloid-derived suppressor cells in experimental models causes
less tumor burden and improves the immune response but doesn´t provide cure.
As cancer is a complex and multifactorial disease the treatment also should be
based on multiple targets.
A recently described target is the renin angiotensin system and its
components (i.e. bradikynin receptors, angiotensin-converting enzyme) as they
may play a role in cancer development. Therefore, our aim was to investigate
the percentage of myeloid-derived suppressor cells at the tumor site and the
possible correlation with bradikynin receptors and angiotensin-converting
enzyme expressions in mice submitted to Urethane-induced lung cancer.
BALB/c mice were either injected with myeloid-derived suppressor cells,
Urethane or only followed for 120 days (control). Lung, spleen, and blood were
phenotyped for myeloid-derived suppressor cells and lung tissue was evaluated
for the expression of renin angiotensin system components.
In tumor-bearing mice it was observed a signiicant increase at the percentage
of myeloid-derived suppressor cells in the spleen along with angiotensin-
converting enzyme increased gene and decreased protein expressions in lung.
Urethane administration was crucial to lung tumor development, to the
increase of peripheral myeloid-derived suppressor cells and to the changes
observed in angiotensin-converting enzyme (ACE).
In conclusion, tumor microenvironment seems to modulate myeloid-derived
suppressor cells expansion and ACE gene and protein expressions. Myeloid-
derived suppressor cells and renin angiotensin system components could be
potential targets for cancer diagnostics and therapy.
Keywords: Lung cancer; Urethane; Myeloid-derived suppressor cells;
Angiotensin-converting enzyme; Bradykinin
It has been shown that one of the mechanisms responsible for
tumor growth is the increased generation of MDSC in bone marrow
followed by their migration to blood and tumor site [3]. hese cells
act suppressing the immune system through the secretion of factors
such as arginase-1 and TGF-β [reviewed in [4, 5]. Another possible
role played by tumor cells and/or MDSC is the interference with
hematopoiesis [3]. he increase of myelopoiesis can lead to the
inhibition in the complete maturation of myeloid cells and thus
to the decrease in the number of inlammatory macrophages and
elevation in the number of suppressive immature myeloid cells [6].
In agreement, we found an increased percentage of MDSC in bone
marrow of mice induced to lung cancer by Urethane administration
[2].
Although MDSCs depletion causes less tumor burden and
Introduction
Our group has shown previously that Urethane-induced lung
cancer leads to an increase in the percentage of myeloid-derived
suppressor cells (MDSC) in spleen and lung along with transforming
growth factor-beta (TGF-β) expression by tumor cells. In addition,
Foxp3
+
cells were elevated in lung tissue of Urethane-injected mice
[1, 2]. hese indings suggest a suppressive status ater lung cancer
induced by Urethane. On the other hand, there was an increase of
toll like receptor 4 (TLR4) expressions in lung tissue and interferon-
gamma (IFN-γ) production ex-vivo by splenocytes suggesting
immune response against tumor [1, 2]. We hypothesized that there
is an imbalance of efector immune response versus suppression/
tolerance culminating with cancer development.
Special Article-Cancer Immunology
Evaluation of Myeloid-derived Suppressor Cells and
Components of Renin Angiotensin System in Urethane-
induced Lung Cancer
Jair Ribeiro Chagas
1,2
, Bruna Visniauskas
1
,
Guiomar Nascimento Gomes
3
and Valquiria
Bueno
4
*
1
Department of Psychobiology, UNIFESP Federal
University of São Paulo, Brazil
2
Department of Biosciences, UNIFESP Federal University
of São Paulo, Brazil
3
Department of Physiology, UNIFESP Federal University
of São Paulo, Brazil
4
Department of Microbiology, Immunology and
Parasitology, UNIFESP Federal University of São Paulo,
Brazil
*Corresponding author: Valquiria Bueno, Department
of Microbiology Immunology and Parasitology, UNIFESP
Federal University of São Paulo, Brazil, Tel: 55 11
989622943; Email: valquiriabueno@hotmail.com
Received: February 19, 2015; Accepted: March 06,
2015; Published: March 09, 2015