The evolving tumor microenvironment From cancer initiation to metastatic outgrowth

Cancers represent complex ecosystems comprising tumor cells and a multitude of non-cancerous cells, embedded in an altered extracellular matrix. The tumor microenvironment (TME) includes diverse immune cell types, cancer-associated fibroblasts, endothelial cells, pericytes, and various additional tissue-resident cell types. These host cells were once considered bystanders of tumorigenesis but are now known to play critical roles in the pathogenesis of cancer. The cellular composition and functional state of the TME can differ extensively depending on the organ in which the tumor arises, the intrinsic features of cancer cells, the tumor stage, and patient characteristics. Here, we review the importance of the TME in each stage of cancer pro-gression, from tumor initiation, progression, invasion, and intravasation to metastatic dissemination and outgrowth. Understanding the complex interplay between tumor cell-intrinsic, cell-extrinsic, and systemic mediators of disease progression is critical for the rational development of effective anti-cancer treatments.

Automated summary

Cancers consist of tumor cells and various non-cancerous cells in an altered extracellular matrix, forming complex ecosystems. The tumor microenvironment (TME) includes different immune cell types, cancer-associated fibroblasts, endothelial cells, pericytes, and other tissue-resident cells, all of which play critical roles in cancer pathogenesis. The composition and function of the TME can vary depending on the organ, cancer cell features, tumor stage, and patient characteristics. Understanding the interplay between tumor cell-intrinsic, cell-extrinsic, and systemic factors is crucial for developing effective anti-cancer treatments.