Tumor microenvironment and the immune system pathway

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Cancer research has been focused on neoplastic cells for many decades, while its influence on surrounding cells and tissues they interact with (the "tumor microenvironment") has not had the same level of attention. Interactions between cancer cells and their stroma is vital for survival and progression of tumors, while also disrupting the surveillance of the immune system for developing tumors. Within a tumor, the stroma can consist of endothelial cells, fibroblasts, adipocytes, and immune cells, which are in close proximity to cancer cells.

The interaction between the host and the cancer cell was first proposed by a 19th century English Surgeon, Stephen Paget, with his “seed and soil” hypothesis. He argued that cancer cells (“the seeds”) selectively metastasize to neoplastic-promoting niches (“soil”).

After "seeding", cancer cells actively corrupt their microenvironment. This is achieved by cancer cells releasing a number of paracrine growth factors, cytokines and metabolites. These factors influence; the generation of de novo vasculature for oxygen supply to the tumor; pertubation of signaling and metabolism in the of surrounding stroma; as well as masking of cancer cells from the immune system to prevent their destruction.These changes to the microenvironment create a niche for the cancer cell that is permissive for their survival as well as growth. The tumor microenvironment is also clinically relevant as it can effect a cancer patient's prognosis and potentially confer drug-resistance, resulting in potential relapse and metastasis.

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