Tumor interstitial fluid analysis enables the study of microenvironment-cell interactions in cancers

Abstract

The tumor microenvironment (TME) plays a crucial role in regulating the state and function of all cell types residing in the tumor and thus impacts many aspects of tumor biology. The importance of the TME has led to an interest in characterizing the composition of the TME and how TME components regulate cancer and stromal cell biology. Tumor interstitial fluid (TIF) is the local perfusate of the TME that carries metabolites, electrolytes, and soluble macromolecules to tumor-resident cells. Recently, techniques to isolate TIF have been coupled with analytical techniques to interrogate the composition of TIF, providing new insight into TME composition. In this review, we will discuss what TIF studies indicate about TME composition and new avenues TIF analysis provides to delineate how the TME regulates tumor biology.

Figure 1.. Interstitial fluid is the liquid phase of the tumor microenvironment.

The tumor microenvironment is comprised of cellular, extracellular matrix, and interstitial fluid components. The interstitial fluid is the perfusate of solid tumors and directly contacts cells residing in the tumor parenchyma carrying metabolites, ions, and soluble macromolecules to these cells. Recently, simple and robust techniques have been developed to isolate interstitial fluid from resected tumors by centrifugation, providing ready access to the interstitial compartment of the TME. Coupled with advances in bioanalytical chemistry enabling high-throughput molecular characterization of small-volume biofluid samples, these advances in tumor interstitial fluid isolation have led to an increasing understanding of the metabolic, proteomic, and ionic composition of the tumor microenvironment.