Issues

A complex network of hyaluronan (HA) and proteoglycans in the tumor microenvironment with high levels of HA (HA^high) forms a physical barrier capable of inhibiting therapeutic monoclonal antibody (mAb) and immune cell access to tumor cells, resulting in a more aggressive tumor phenotype in several solid tumor types. Microscopic cell imaging shows that a physical barrier surrounding HA^high tumor cell restricts human NK cells from accessing the tumor cell. These results demonstrate that HA depletion by PEGPH20 removes this barrier and allows increased mAb and immune cell access to the tumor cell, resulting in more efficient antibody-dependent cell-mediated cytotoxicity (ADCC)-dependent tumor cell killing. For details, see the article by Singha and colleagues on page 523.