Tumor interstitial fluid formation, characterization, and clinical implications

The interstitium, situated between the blood and lymph vessels and the cells, consists of a solid or matrix phase and a fluid phase representing the tissue microenvironment. In the present review, we focus on the interstitial fluid phase of solid tumors, the tumor interstitial fluid (TIF), i.e., the fluid bathing the tumor and stroma cells, also including immune cells. This is a component of the internal milieu of a solid tumor that has attracted regained attention. Access to this space may provide important insight into tumor development and therapy response. TIF is formed by transcapillary filtration, and since this fluid is not readily available we discuss available techniques for TIF isolation, results from subsequent characterization and implications of recent findings with respect to fluid filtration and uptake of macromolecular therapeutic agents. There appear to be local gradients in signaling substances from neoplastic tissue to plasma that may provide new understanding of tumor biology. The development of sensitive proteomic technologies has made TIF a valuable source for tumor specific proteins and biomarker candidates. Potential biomarkers will appear locally in high concentrations in tumors and may eventually be found diluted in the plasma. Access to TIF that reliably reflects the local tumor microenvironment enables identification of substances that can be used in early detection and monitoring of disease.