The tumor microenvironment in esophageal cancer

• Published in: Oncogene Vol. 35; no. 41; pp. 5337 - 5349
• Main Authors: Lin, E W, Karakasheva, T A, Hicks, P D, Bass, A J, Rustgi, A K
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 13.10.2016
• Subjects: Angiogenesis; Apoptosis; Apoptosis - genetics; Apoptosis - immunology; Cancer; Care and treatment; Cell Cycle Checkpoints - genetics; Cell Cycle Checkpoints - immunology; Cell death; Development and progression; Esophageal cancer; Esophageal Neoplasms - genetics; Esophageal Neoplasms - pathology; Esophagus; Extracellular matrix; Genetic aspects; Growth factors; Humans; Immune checkpoint; Immunoregulation; Inflammation; Inflammation - genetics; Inflammation - immunology; Inflammation - pathology; Innovations; Leukocyte migration; Lymphocytes T; Macrophages; Medical prognosis; Metastases; Microbiology; Molecular modelling; Molecular targeted therapy; Neoplasm Invasiveness - immunology; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - pathology; Suppressor cells; T-Lymphocytes, Regulatory - immunology; Tumor cells; Tumor microenvironment; Tumor Microenvironment - genetics; Tumorigenesis; Tumors
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/onc.2016.34

Esophageal cancer is a deadly disease, ranking sixth among all cancers in mortality. Despite incremental advances in diagnostics and therapeutics, esophageal cancer still carries a poor prognosis, and thus, there remains a need to elucidate the molecular mechanisms underlying this disease. There is accumulating evidence that a comprehensive understanding of the molecular composition of esophageal cancer requires attention to not only tumor cells but also the tumor microenvironment (TME), which contains diverse cell populations, signaling factors and structural molecules that interact with tumor cells and support all stages of tumorigenesis. In esophageal cancer, environmental exposures can trigger chronic inflammation, which leads to constitutive activation of pro-inflammatory signaling pathways that promote survival and proliferation. Antitumor immunity is attenuated by cell populations such as myeloid-derived suppressor cells and regulatory T cells, as well as immune checkpoints like programmed death-1. Other immune cells such as tumor-associated macrophages can have other pro-tumorigenic functions, including the induction of angiogenesis and tumor cell invasion. Cancer-associated fibroblasts secrete growth factors and alter the extracellular matrix to create a tumor niche and enhance tumor cell migration and metastasis. Further study of how these TME components relate to the different stages of tumor progression in each esophageal cancer subtype will lead to development of novel and specific TME-targeting therapeutic strategies, which offer considerable potential especially in the setting of combination therapy.