Tumors are often encapsulated by extracellular matrix (ECM), which can act as a barrier to entry by immune cells. In The Journal of Clinical Investigation, Smyth and colleagues investigate the role of heparanase—an enzyme involved in degrading the ECM—in controlling the entry of natural killer (NK) cells into the tumor mass. Resting NK cells express only low levels of heparanase, but amounts of the active version of the enzyme increase dramatically after cell stimulation. Conditional knockout of heparanase in NK cells has no effect on their development, function, proliferation or distribution. However, in several different models, mice with heparanase-deficient NK cells have an impaired ability to control tumors but show increased frequency of exclusion from the tumor mass. The expression of heparanase by NK cells is therefore important for their invasion of tumors, probably owing to degradation of the ECM capsule.

J. Clin. Invest. (21 June 2017) http://dx.doi.org/10.1172/JCI92958