A. Menoret et al., CO-SEGREGATION OF TUMOR IMMUNOGENICITY WITH EXPRESSION OF INDUCIBLE BUT NOT CONSTITUTIVE HSP70 IN RAT COLON CARCINOMAS, The Journal of immunology, 155(2), 1995, pp. 740-747
Recent results have shown the importance of heat-shock proteins (hsp)
in immune reactions. In addition, immunization against hsp purified fr
om some immunogenic tumors specifically protects animals from a challe
nge with the tumor from which the hsp were purified. The protection is
dependent on the association between hsp and immunogenic peptides. Us
ing a model of rat colon carcinoma, we studied the importance of hsp70
expression in determining the tumorigenicity of cancer cells in immun
ocompetent syngeneic animals. Various clones with distinct tumorigenic
potentials have been derived from the same parental tumor. Some clone
s are tumorigenic and others are rejected through an immune-based mech
anism. It was observed that among all parameters tested, immunogenicit
y of tumors co-segregated with expression of inducible hsp70 but not w
ith constitutive hsc70. Variants were obtained from a highly tumorigen
ic 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 tumorigenici
ty. inversely, the REGb variant (REGR73), selected after in vivo growt
h in partially immunosuppressed rats, acquired tumorigenicity and lost
the ability to synthesize hsp70. Expression of other immunologic medi
ators such as intercellular adhesion molecule-1, MHC I, and MHC II did
not co-segregate with tumor immunogenicity. Depletion experiments sho
wed that the immunity elicited by these tumors involves TCR-alpha beta
-bearing T cells. Such observations imply that, in this experimental m
odel, inducible but not constitutive hsp70 is involved in immunogenici
ty of tumors.