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Effector‐phase tolerance: another mechanism of how cancer escapes antitumor immune response
Author(s) -
Frey Alan B.,
Monu Ngozi
Publication year - 2006
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1105628
Subject(s) - immune system , biology , antigen , immunology , cancer , effector , cancer research , immune tolerance , tumor microenvironment , tumor antigen , cytotoxic t cell , cd8 , cancer cell , cancer vaccine , lytic cycle , immunotherapy , in vitro , biochemistry , virus , genetics
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 ∼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 [1, 2]. 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% [2]. 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.