Abstract
Abstract Cancer immunoediting is the process wherein the immune system not only protects against tumor development but also promotes outgrowth of tumors with reduced immunogenicity. Although we and others identified several key immune components that participate in this process, we know very little about the targets of cancer immunoediting. In this study we used a highly immunogenic methylcholanthrene induced sarcoma cell line (d42m1) to ask whether tumor antigens can be immunoediting targets. Like most unedited MCA sarcomas, d42m1 cells form tumors when transplanted into immunodeficient mice but are rejected in naive syngeneic wild type (WT) mice. We identified two antigens of d42m1 by expression cloning: a point mutant of spectrin-β2 and a point mutant of M-phase phosphoprotein 8 (MPP8). In WT mice, d42m1 occasionally produces escape variants lacking mutant spectrin-β2 but maintaining expression of mutant MPP8 that can form tumors in naive WT mice. Enforced expression of mutant but not WT spectin-β2 into escape variant cell lines converted them into regressors. Analysis of the parental d42m1 cell line revealed that only 80% of d42m1 clones expressed mutant spectrin-β2 whereas 100% expressed mutant MPP8. Only spectrin-β2 expressing d42m1 clones were rejected in WT mice. Thus, mutant spectrin-β2 is not only the major rejection antigen of d42m1 sarcoma cells but is the target of a cancer immunoediting immunoselection process that facilitates tumor escape from immune control.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call