Chemically induced
tumors of inbred mice elicit immunity in animals in which the
tumors are induced and in other animals of the same inbred stock. The immunity is specific for each
tumor: even two
tumors induced in one animal with the same
carcinogen are not cross-reactive. Immunity to
cancer has since been observed in the case of
sarcomas and
carcinomas induced by a number of chemical and physical
carcinogens and in several species, including mice, rats, and guinea pigs. The nature of molecules which mediate immunity to
tumors is a central question in
cancer immunology. A small number of such molecules have been biochemically defined. Of these, some are
viral antigens expressed in
tumor cells, while the relationship of some others to
viral antigens is unclear. A surprising majority of nonviral
tumor antigens have turned out to bear homology with stress-induced
proteins. Four families of such molecules are discussed: the gp96 (hsp100) and p84/86 (hsp90)
antigens of chemically induced mouse
sarcomas, hsp70
antigens of
tumors obtained by transfection of normal rat fetal fibroblasts with an H-ras oncogene, and the albuminoid
antigens of murine
melanomas and a rat
histiocytoma. (
Albumin-like
antigens are included among the stress-induced
proteins because
albumin, though constitutively expressed in adult tissues, is heat shock inducible in fetal liver.) Each of these
antigens is a moderately abundant
protein, present not only in
tumors but also in normal tissues. Administration of each of these
antigen preparations from the
tumor, but not from normal tissue, renders the animal immune to challenge with live cells of the
tumor from which the
antigens are prepared. And yet, no structural differences in the
antigens have been observed between normal tissues and
tumors. It is suggested that these stress-induced
proteins may not be
tumor antigens per se, but may be carriers of immunogenic moieties such as short
peptides. The stress-induced
proteins may therefore serve either as
antigen-presenting molecules like the MHC-encoded molecules or as accessory molecules in the presentation of
antigens by MHC molecules. The ability of stress-induced
proteins to bind to a variety of molecules, including
peptides, is consistent with this possibility.