Co-segregation of tumor immunogenicity with expression of inducible but not constitutive hsp70 in rat colon carcinomas

Abstract

Recent results have shown the importance of heat-shock proteins (hsp) in immune reactions. In addition, immunization against hsp purified from some immunogenic tumors specifically protects animals from a challenge with the tumor from which the hsp were purified. The protection is dependent on the association between hsp and immunogenic peptides. Using a model of rat colon carcinoma, we studied the importance of hsp70 expression in determining the tumorigenicity of cancer cells in immunocompetent syngeneic animals. Various clones with distinct tumorigenic potentials have been derived from the same parental tumor. Some clones are tumorigenic and others are rejected through an immune-based mechanism. It was observed that among all parameters tested, immunogenicity of tumors co-segregated with expression of inducible hsp70 but not with constitutive hsc70. Variants were obtained from a highly tumorigenic clone (PROb) and from a regressive clone (REGb). The PROb variant (Ph8), selected by repeated sublethal heat shocks, showed an increased capacity for hsp70 synthesis concomitant with a decreased tumorigenicity. Inversely, the REGb variant (REGR73), selected after in vivo growth in partially immunosuppressed rats, acquired tumorigenicity and lost the ability to synthesize hsp70. Expression of other immunologic mediators such as intercellular adhesion molecule-1, MHC I, and MHC II did not co-segregate with tumor immunogenicity. Depletion experiments showed that the immunity elicited by these tumors involves TCR-alpha beta-bearing T cells. Such observations imply that, in this experimental model, inducible but not constitutive hsp70 is involved in immunogenicity of tumors.