Effector-phase tolerance: another mechanism of how cancer escapes antitumor immune response

Abstract: Growth of cancer in rodent models and in patients elicits immune responses directed toward various antigens expressed by the trans-formed cell. Clearly though, as most tumors grow, unmanipulated antitumor immune re-sponses are incapable of eliminating cancer. Over the past 15 years, antitumor immuno-globulin and T cells have been used to identify tumor antigens, which in turn, have served as the basis for therapeutic vaccine trials [1, 2]. How-ever, experimental cancer vaccines, although in some patients result in elimination of large tumor burdens, have a low frequency of long-term can-cer remission in most patients, ca. <5 % [3]. Therefore, as tumors express antigens that dis-tinguish themselves from nontransformed cells in immunological terms (i.e., elicit immune re-sponses 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. Al-though there are several types of T cell toler-ance, mature, antigen-specific CD8 T cells iso-lated from tumors are lytic-defective, implying that the tumor microenvironment inactivates the antitumor effector phase. The nature of the func-tional local tolerance to antitumor immune re-sponse is the subject of this review. J. Leukoc