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Concept
Tumor microenvironment
Summary
The tumor microenvironment (TME) is the environment around a tumor, including the surrounding blood vessels, immune cells, fibroblasts, signaling molecules and the extracellular matrix (ECM). The tumor and the surrounding microenvironment are closely related and interact constantly. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells.
The importance of a stromal microenvironment, especially "wound" or regenerating tissue, has been recognized since the late 1800s. The interplay between the tumor and its microenvironment was part of Stephen Paget's 1889 "seed and soil" theory, in which he postulated that metastases of a particular type of cancer ("the seed") often metastasizes to certain sites ("the soil") based on the similarity of the original and secondary tumor sites.
Its role in blunting an immune attack awaited the discovery of adaptive cellular immunity. In 1960, Klein and colleagues found that in mice, primary methylcholanthrene-induced sarcomas exhibited an antitumor immune response mediated by lymph node cells to cancer cells derived from the primary tumor. This immune response did not however affect the primary tumor. The primary tumor instead established a microenvironment that is functionally analogous to that of certain normal tissues, such as the eye.
Later, mice experiments by Halachmi and Witz showed that for the same cancer cell line, greater tumorigenicity was evident in vivo than the same strain inoculated in vitro.
Unambiguous evidence for the inability in humans of a systemic immune response to eliminate immunogenic cancer cells was provided by Boon's 1991 studies of antigens that elicit specific CD8+ T cell responses in melanoma patients. One such antigen was MAGE-A1. The coexistence of a progressing melanoma with melanoma-specific T cells implicitly does not involve immunoediting, but does not exclude the possibility of TME immune suppression.
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