Tumor-induced antibodies resemble the response to tissue damage

Abstract

Tumor-associated antibodies are frequently detected in cancer patients. To ask whether the recognized antigens are rejection antigens, we screened a cDNA expression library of the mouse TS/A tumor with TS/A-immune serum and isolated 8 IgG-reactive clones, representing self-antigens that were expressed in normal tissues and other tumor lines. Three of the antigens had previously been identified in the human system by this cloning strategy. None of the antigens revealed to be a rejection antigen in normal mice demonstrated by an otherwise effective plasmid immunization. For one of the identified antigens, alpha-catenin, it is shown that the induction of IgG antibodies by protein immunization does not correlate with tumor rejection. For another antigen, vimentin, it is shown that vimentin-deficient but not vimentin-competent mice reject vimentin-expressing tumors indicating T -cell tolerance despite the fact that tumor cell immunization induces antivimentin IgG antibodies. Tissue damage induced by adenovirus infection induced an antibody response similar to tumor cell immunization, exemplified with 2 of the antigens. We conclude that the tumor-induced antibodies mirror tissue damage and that the antibody-inducing antigens can serve as rejection antigens if they are recognized as foreign.