Growth of
cancer in rodent models and in patients elicits immune responses directed toward various
antigens expressed by the transformed cell. Clearly though, as most
tumors grow, unmanipulated antitumor immune responses are incapable of eliminating
cancer. Over the past approximately 15 years, antitumor
immunoglobulin and T cells have been used to identify
tumor antigens, which in turn, have served as the basis for therapeutic
vaccine trials. However, experimental
cancer vaccines, although in some patients result in elimination of large
tumor burdens, have a low frequency of long-term
cancer remission in most patients, ca. <5%. Therefore, as
tumors express
antigens that distinguish themselves from nontransformed cells in immunological terms (i.e., elicit immune responses to growth of primary
tumor and can target
tumor cells in vivo), and
tumor vaccines prime unsuccessful antitumor immune responses in patients, it is likely that growth of
cancer induces immune tolerance to
tumor cells. Although there are several types of T cell tolerance, mature,
antigen-specific CD8+ T cells isolated from
tumors are lytic-defective, implying that the tumor microenvironment inactivates the antitumor effector phase. The nature of the functional local tolerance to antitumor immune response is the subject of this review.