The role of the hypoxia-Nrp-1 axis in the activation of M2-like tumor-associated macrophages in the tumor microenvironment of cervical cancer

2018 ◽  
Vol 58 (3) ◽  
pp. 388-397 ◽  
Author(s):  
Xiao-Jing Chen ◽  
Sha Wu ◽  
Rui-Ming Yan ◽  
Liang-Sheng Fan ◽  
Lan Yu ◽  
...  
2018 ◽  
Vol 45 (1) ◽  
pp. 356-365 ◽  
Author(s):  
Xiaoming Zhong ◽  
Bin Chen ◽  
Zhiwen Yang

Tumor-associated macrophages (TAMs) are one of the most abundant immune cells in the tumor microenvironment, and they play a pivotal role in prompting the various tumor growth. However, the role of TAMs in colorectal carcinoma (CRC) is controversial, because a few papers report that TAMs is beneficial to CRC patients. In this review, we discuss the good or bad roles of TAMs in CRC progression. Interestingly, recent studies provide strong evidence that TAMs facilitate CRC growth, but do not exert tumor suppressive activities. TAMs can stimulate CRC growth by altering extracellular matrix remodeling, tumor metabolism, angiogenesis, as well as the tumor microenvironment. Therefore, TAMs could serve as a target for CRC therapeutic treatment.


2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Daria Capece ◽  
Mariafausta Fischietti ◽  
Daniela Verzella ◽  
Agata Gaggiano ◽  
Germana Cicciarelli ◽  
...  

Hepatocellular carcinoma (HCC) is one of the most common and aggressive human cancers worldwide. HCC is an example of inflammation-related cancer and represents a paradigm of the relation occurring between tumor microenvironment and tumor development. Tumor-associated macrophages (TAMs) are a major component of leukocyte infiltrate of tumors and play a pivotal role in tumor progression of inflammation-related cancer, including HCC. Several studies indicate that, in the tumor microenvironment, TAMs acquire an M2-polarized phenotype and promote angiogenesis, metastasis, and suppression of adaptive immunity through the expression of cytokines, chemokines, growth factors, and matrix metalloproteases. Indeed, an established M2 macrophage population has been associated with poor prognosis in HCC. The molecular links that connect cancer cells and TAMs are not completely known, but recent studies have demonstrated that NF-κB, STAT-3, and HIF-1 signaling pathways play key roles in this crosstalk. In this paper, we discuss the current knowledge about the role of TAMs in HCC development, highlighting the role of TAM-derived cytokines, chemokines, and growth factors in the initiation and progression of liver cancer and outlining the signaling pathways involved in the interplay between cancer cells and TAMs.


2021 ◽  
Author(s):  
Nai-Wei Yao ◽  
Hsiu-Ting Lin ◽  
Ya-Lin Lin ◽  
Khamushavalli Geeviman ◽  
Fang Liao ◽  
...  

Abstract Background: Glioblastoma is the most aggressive subtype of brain tumors. The major component of tumor microenvironment in glioblastoma is tumor-associated macrophages (TAMs), which are associated with enhanced malignancy of glioblastoma. The polarization of macrophages to the pro-inflammatory M1 or anti-inflammatory M2 subtypes governed by the context of tumor microenvironment may dictate the aggressiveness and outcome of glioblastoma. Given that the immune responses to tumors vary distinctively among individuals due to intrinsic, environmental and genetic factors and that TAMs display a high level of diversity and plasticity, we aimed to examine the effects of differential polarization of TAMs on the glioblastoma development by implanting C6 glioma into brains of Sprague–Dawley (SD) and Wistar rats; these two rats have different genetic background and host microenvironment during tumor development. Methods: Sprague–Dawley (SD) and Wistar rats were implanted with C6 glioma in the brain. The measurement of tumor volumes, tumor morphology and tumor growth in C6 glioma implanted brains were measured by multi-parametric magnetic resonance imaging (MRI). Immunofluorescence staining was performed to analyze tumor angiogenesis and M1 and M2 TAMs in C6 gliomas. Results: By multi-parametric MRI measurement, C6 gliomas developed in the SD rats were characterized with enlarged tumors, accompanied with shorter animal survival. In comparison to the gliomas in Wistar rats, the accelerated tumor growth in SD rats was associated with greater extent of angiogenesis accompanied with higher levels of VEGF/VEGFR2. In support, C6 gliomas in SD rats were filtrated with TAMs characterized with a higher M2/M1 ratio, in contrast to the TAMs of a high M1/M2 ratio in Wistar rats. Attempts were made to shift the M2/M1 balance. Administration of the cytokine IFN-γ that induces M1 TAMs to SD rats greatly suppressed glioma formation, accompanied with a remarkable increase of M1 TAMs. Administration of the cytokines IL-4 plus IL-10 that induces M2 TAMs significantly promoted glioma growth in the Wistar rats, associated with an increase in the M2 TAMs. Conclusions: These results demonstrate an important role of TAMs in glioma pathogenesis and the crucial role of microenvironment in dictating the polarization of TAMs, suggesting that targeting or repolarization of TAMs may serve as an effective intervention for gliomas.


2020 ◽  
Vol 10 (4) ◽  
pp. 556-565
Author(s):  
Somaiyeh Malekghasemi ◽  
Jafar Majidi ◽  
Amir Baghbanzadeh ◽  
Jalal Abdolalizadeh ◽  
Behzad Baradaran ◽  
...  

Tumor microenvironment consists of malignant and non-malignant cells. The interaction of these dynamic and different cells is responsible for tumor progression at different levels. The non-malignant cells in TME contain cells such as tumor-associated macrophages (TAMs), cancer associated fibroblasts, pericytes, adipocytes, T cells, B cells, myeloid-derived suppressor cells (MDSCs), tumor-associated neutrophils (TANs), dendritic cells (DCs) and Vascular endothelial cells. TAMs are abundant in most human and murine cancers and their presence are associated with poor prognosis. The major event in tumor microenvironment is macrophage polarization into tumor-suppressive M1 or tumor-promoting M2 types. Although much evidence suggests that TAMS are primarily M2-like macrophages, the mechanism responsible for polarization into M1 and M2 macrophages remain unclear. TAM contributes cancer cell motility, invasion, metastases and angiogenesis. The relationship between TAM and tumor cells lead to used them as a diagnostic marker, therapeutic target and prognosis of cancer. This review presents the origin, polarization, role of TAMs in inflammation, metastasis, immune evasion and angiogenesis as well as they can be used as therapeutic target in variety of cancer cells. It is obvious that additional substantial and preclinical research is needed to support the effectiveness and applicability of this new and promising strategy for cancer treatment.


2016 ◽  
Vol 16 (9) ◽  
pp. 1133-1141 ◽  
Author(s):  
Jie Zhu ◽  
Qiaoming Zhi ◽  
Binhua P. Zhou ◽  
Min Tao ◽  
Jingyi Liu ◽  
...  

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1086
Author(s):  
Tomohiro Fujiwara ◽  
John Healey ◽  
Koichi Ogura ◽  
Aki Yoshida ◽  
Hiroya Kondo ◽  
...  

Sarcomas are complex tissues in which sarcoma cells maintain intricate interactions with their tumor microenvironment. Tumor-associated macrophages (TAMs) are a major component of tumor-infiltrating immune cells in the tumor microenvironment and have a dominant role as orchestrators of tumor-related inflammation. TAMs promote tumor growth and metastasis, stimulate angiogenesis, mediate immune suppression, and limit the antitumor activity of conventional chemotherapy and radiotherapy. Evidence suggests that the increased infiltration of TAMs and elevated expression of macrophage-related genes are associated with poor prognoses in most solid tumors, whereas evidence of this in sarcomas is limited. Based on these findings, TAM-targeted therapeutic strategies, such as inhibition of CSF-1/CSF-1R, CCL2/CCR2, and CD47/SIRPα, have been developed and are currently being evaluated in clinical trials. While most of the therapeutic challenges that target sarcoma cells have been unsuccessful and the prognosis of sarcomas has plateaued since the 1990s, several clinical trials of these strategies have yielded promising results and warrant further investigation to determine their translational benefit in sarcoma patients. This review summarizes the roles of TAMs in sarcomas and provides a rationale and update of TAM-targeted therapy as a novel treatment approach for sarcomas.


2019 ◽  
Vol 8 (10) ◽  
pp. 4709-4721 ◽  
Author(s):  
Jing Wang ◽  
Danyang Li ◽  
Huaixing Cang ◽  
Bo Guo

2021 ◽  
Author(s):  
Fan Guo ◽  
Wei na Kong ◽  
Gang Zhao ◽  
Zhen zhen Cheng ◽  
Le Ai ◽  
...  

Tumor microenvironment (TME) plays a particularly important role in the progression, invasion and metastasis of cervical carcinoma (CC). Tumor-associated macrophages (TAMs) are significant components of the tumor microenvironment in CC. However, the results of studies on the correlation between TAMs and progression in CC are still controversial. This research aimed to investigate the relationship between TAMs infiltration and progression in CC. A total of 100 patients with CC were included in the study. The correlation between TAMs and clinicopathologic features was studied. Besides, a systematic literature search was conducted from legitimate electronic databases to specifically evaluate the role of TAMs in TME of cervical carcinoma. In the meta-analysis, high stromal CD68+ TAMs density was relevant to lymph node metastasis (WMD = 11.89, 95% CI 5.30 to 18.47). At the same time, CD163+ M2 TAM density was associated with lymph node metastasis (OR = 2.42, 95% CI 1.09 to 5.37; WMD = 39.37, 95% CI 28.25 to 50.49) and FIGO stage (WMD = -33.60, 95% CI -45.04 to -22.16). This was further confirmed in the experimental study of 100 tissues of cervical cancer. It supported a critical role of TAMs as a prospective predictor of cervical cancer. In conclusion, CD68+ TAM and CD163+ M2 TAM infiltration in CC were associated with tumor progression. And CD163+ M2 TAM infiltration was associated with more advanced FIGO stage and lymph node metastasis in CC.


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