Infiltration of Alternatively Activated Macrophages in Cancer Tissue Is Associated with MDSC and Th2 Polarization in Patients with Esophageal Cancer
et al. (2014) Infiltration of Alternatively Activated Macrophages in Cancer Tissue Is Associated with MDSC and
Th2 Polarization in Patients with Esophageal Cancer. PLoS ONE 9(8): e104453. doi:10.1371/journal.pone.0104453
Infiltration of Alternatively Activated Macrophages in Cancer Tissue Is Associated with MDSC and Th2 Polarization in Patients with Esophageal Cancer
Jingjing Gao 0
Yumin Wu 0
Zhaoliang Su 0
Prince Amoah Barnie 0
Zhijun Jiao 0
Qingli Bie 0
Liwei Lu 0
Shengjun Wang 0
Huaxi Xu 0
Jacques Zimmer, Centre de Recherche Public de la Sante (CRP-Sante), Luxembourg
0 1 Department of Immunology, School of Medical Science and Laboratory Medicine, Jiangsu University , Zhenjiang , P. R. China , 2 Department of Laboratory Medicine, Affiliated Hospital of Jiangsu University , Zhenjiang , P. R. China , 3 Department of Laboratory Medicine, Suzhou Hospital Affiliated to Nanjing Medical University , Suzhou , P. R. China , 4 Department of Pathology and Centre of Infection and Immunology, The University of Hong Kong , Hong Kong , P. R. China
Myeloid derived suppressor cells (MDSCs) expand in cancer bearing hosts and contribute to tumor immune evasion. M2 macrophages constitute a major cellular component of cancer-related inflammation. However, the correlation between circulating MDSCs and infiltrating M2 macrophages in tumor tissues from patients with esophageal cancer (ECA), and its potential relationship with the polarization of Th2 cells remain unclear. In the present study, we showed the level of MDSCs in PBMC and Arg1 in plasma were significantly elevated in ECA patients, and the increased ratio of MDSC in PBMC was closely related to the expression of CD163 in cancer tissues. In addition, the ECA patients exhibited remarkable increases in the mRNA levels of IL-4 and GATA3, as well as the protein levels of IL-13 and IL-6, but IFN-c and IL-12 in peripheral blood were decreased. Our data indicate that the increased Th2 cytokines are associated with MDSCs and M2 macrophages polarization, and foster the infiltration of CD163+M2 macrophages in cancer tissues, which promote the formation of immunosuppressive microenvironment in ECA patients.
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Funding: This work was supported by grants from the National Natural Science Foundation of China (31270947, 31170849 and 30972748, http://www.nsfc.gov.
cn/), Natural Science Foundation of Jiangsu Province (BK2011472) and the Postdoctoral Foundation of China (2012M511705). The funders had no role in study
design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
" These authors are co-first authors on this work.
Esophageal cancer (ECA) is one of the most common
malignancies all over the world and the fourth leading cancer
death in China [13]. There are increasing evidences of the crucial
role of the immune system in malignant tumors, but the precise
mechanisms of immune modulation in ECA patients remain
elusive. In the past decade, the role of the immunosuppressive and
cancer-promoting myelomonocytic compartment within the
tumor environment has also received a great deal of attention
[4]. Although mechanisms are incompletely understood, cancer
promotes the accumulation of a heterogeneous pool of bone
marrow-derived immature, poorly differentiated myelomonocytic
cells (monocytes, neutrophils, immature macrophages and
dendritic cells), called myeloid derived suppressor cells (MDSCs),
which are major host component contributing to the
immunosuppressive environment. In pathological conditions, a partial
block in the differentiation of immature myeloid cells into matured
myeloid cells results in an expansion of MDSCs [5]. Recently, it
has become clear that the suppressive activity of MDSCs requires
various factors which promote their expansion or induce their
activation. These factors, which include IL-4, IL-13, ligands for
Toll-like receptors (TLRs), and transforming growth factor-b
(TGF-b), activate several different signalling pathways in MDSCs
that involve STAT6 and nuclear factor-kB (NF-kB).
Similar to MDSCs, macrophages are a diverse population of
myeloid cells which undergo specific differentiation depending on
the stimulating agents, as documented extensively. Recent
immunological studies have identified two distinct states of the
polarized macrophage activation: the classically activated (or M1)
and the alternatively activated (or M2) macrophage phenotypes.
M1 macrophages are typically activated by IFN-c and LPS,
whereas M2 macrophages are activated by IL-4 and IL-13 [6]. M1
macrophages are tumoricidal and promote tumor rejection,
whereas M2 macrophages promote tumor progression [79].
Both M2 macrophages and MDSCs are a major source of
immunosuppression that allows tumor-escape from effective
anticancer responses, but no information on the relationship between
M2 macrophages and MDSCs in the development of esophageal
cancer is currently available.
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