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

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.