Deciphering the Key Features of Malignant Tumor Microenvironment for Anti-cancer Therapy

Shang, Bingxue; Zhang, Gaochuan; Pan, Yanyan; Zhou, Quansheng

doi:10.1007/s12307-012-0108-9

Cited by 10 publications

(6 citation statements)

References 100 publications

(186 reference statements)

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“…A growing body of evidence suggests that several oncogenes may directly influence the tumor microenvironment through regulating the expression of soluble ligands and cytokines (27). Secretion of these factors may act in paracrine to stimulate and transform neighboring cells, while recruiting myeloid derived suppressor cells (MDSC) and Tregs, which are associated with a poor prognosis, in contrast to the tumor infiltrating cytotoxic lymphocytes, which are associated with a better prognosis (28).…”

Section: Discussionmentioning

confidence: 99%

Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors

et al. 2013

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The success in lung cancer therapy with Programmed Death (PD)-1 blockade suggests that immune escape mechanisms contribute to lung tumor pathogenesis. We identified a correlation between Epidermal Growth Factor Receptor (EGFR) pathway activation and a signature of immunosuppression manifested by upregulation of PD-1, PD-L1, cytotoxic T lymphocyte antigen-4 (CTLA-4), and multiple tumor-promoting inflammatory cytokines. We observed decreased cytotoxic T cells and increased markers of T cell exhaustion in mouse models of EGFR-driven lung cancer. PD-1 antibody blockade improved the survival of mice with EGFR-driven adenocarcinomas by enhancing effector T cell function and lowering the levels of tumor-promoting cytokines. Expression of mutant EGFR in bronchial epithelial cells induced PD-L1, and PD-L1 expression was reduced by EGFR inhibitors in non-small cell lung cancer cell lines with activated EGFR. These data suggest that oncogenic EGFR signaling remodels the tumor microenvironment to trigger immune escape, and mechanistically link treatment response to PD-1 inhibition.

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Section: Discussionmentioning

confidence: 99%

Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors

et al. 2013

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“…It is not only that 'normal cells' could turn into 'conscripted or subverted cells' to establish a cancer but some other normal cells would be triggered by the mutant cancer cells to help them proliferate and survive. These include normal host cells such as endothelial cells, fibroblasts, monocytes/macrophages, mesenchymal cells and cells of hematopoietic origin, at sites distant from and local to the site at which malignant transformation occurs (154). In addition, host and cancer cell interactions are occurring within a network that governs and influences both cancer and host cell properties.…”

Section: Discussionmentioning

confidence: 99%

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: focus on the cancer hallmark of tumor angiogenesis

Hu¹,

Brooks

Dormoy

et al. 2015

CARCIN

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One of the important 'hallmarks' of cancer is angiogenesis, which is the process of formation of new blood vessels that are necessary for tumor expansion, invasion and metastasis. Under normal physiological conditions, angiogenesis is well balanced and controlled by endogenous proangiogenic factors and antiangiogenic factors. However, factors produced by cancer cells, cancer stem cells and other cell types in the tumor stroma can disrupt the balance so that the tumor microenvironment favors tumor angiogenesis. These factors include vascular endothelial growth factor, endothelial tissue factor and other membrane bound receptors that mediate multiple intracellular signaling pathways that contribute to tumor angiogenesis. Though environmental exposures to certain chemicals have been found to initiate and promote tumor development, the role of these exposures (particularly to low doses of multiple substances), is largely unknown in relation to tumor angiogenesis. This review summarizes the evidence of the role of environmental chemical bioactivity and exposure in tumor angiogenesis and carcinogenesis. We identify a number of ubiquitous (prototypical) chemicals with disruptive potential that may warrant further investigation given their selectivity for high-throughput screening assay targets associated with proangiogenic pathways. We also consider the cross-hallmark relationships of a number of important angiogenic pathway targets with other cancer hallmarks and we make recommendations for future research. Understanding of the role of low-dose exposure of chemicals with disruptive potential could help us refine our approach to cancer risk assessment, and may ultimately aid in preventing cancer by reducing or eliminating exposures to synergistic mixtures of chemicals with carcinogenic potential.

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“…Chronic inflammation is important in the development of cancer and inflammatory cells are fundamental in the genesis of tumor microenvironment. Cancer is generally defined as an imbalance between the TME‐stimulating and promoting forces and the TME‐inhibiting forces (Shang et al, ). In cancer, promoting forces are predominant on inhibiting forces.…”

Section: Future Directionmentioning

confidence: 99%

Tumor Microenvironment Versus Cancer Stem Cells in Cholangiocarcinoma: Synergistic Effects?

Romano

Francesco

Gringeri

et al. 2015

Journal Cellular Physiology

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Cholangiocarcinoma (CCAs) may be defined as tumors that derived from the biliary tree with the differentiation in the biliary epithelial cells. This tumor is malignant, extremely aggressive with a poor prognosis. It can be treated surgically and its pathogenesis is poorly understood. The tumor microenvironment (TME) is a very important factor in the regulation of tumor angiogenesis, invasion, and metastasis. Besides cancer stem cells (CSCs) can modulate tumor growth, stroma formation, and migratory capability. The initial stage of tumorigenesis is characterized by genetic mutations and epigenetic alterations due to intrinsic factors which lead to the generation of oncogenes thus inducing tumorigenesis. CSCs may result from precancerous stem cells, cell de-differentiation, normal stem cells, or an epithelial-mesenchymal transition (EMT). CSCs have been found in the cancer niche, and EMT may occur early within the tumor microenvironment. Previous studies have demonstrated evidence of cholangiocarcinoma stem cells (CD133, CD24, EpCAM, CD44, and others) and the presence of these markers has been associated with malignant potential. The interaction between TME and cholangiocarcinoma stem cells via signaling mediators may create an environment that accommodates tumor growth, yielding resistance to cytotoxic insults (chemotherarapeutic). While progress has been made in the understanding of the mechanisms, the interactions in the tumorigenic process still remain a major challenge. Our review, addresses recent concepts of TME-CSCs interaction and will emphasize the importance of early detection with the use of novel diagnostic mechanisms such as CCA-CSC biomarkers and the importance of tumor stroma to define new treatments. J. Cell. Physiol. 231: 768-776, 2016. © 2015 Wiley Periodicals, Inc.

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Deciphering the Key Features of Malignant Tumor Microenvironment for Anti-cancer Therapy

Cited by 10 publications

References 100 publications

Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors

Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors

Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment: focus on the cancer hallmark of tumor angiogenesis

Tumor Microenvironment Versus Cancer Stem Cells in Cholangiocarcinoma: Synergistic Effects?

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