Does the serpin PI-9 protect tumor cells?
The report of Godal et al1 raises an important issue on the effectiveness of apoptosis inhibitors in preventing death induced by cytotoxic lymphocytes (CLs) in clinically relevant settings. A large variety of tumors express apoptosis inhibitors such as Bcl-2 and PI-9, which protect cells from granzyme B (GrB)–induced apoptosis in in vitro settings,2–4 and were thus proposed to induce immune escape of tumors. Based on in vitro assays Godal et al1 now claim that expression of these apoptotic regulators is irrelevant for CL sensitivity of lymphomas and therefore unlikely to affect immunotherapy of lymphomas. However, a major limitation of this conclusion is that it is based on in vitro analysis, and current data suggest that this doesn’t necessarily represent the in vivo situation.
