The Role of Defective MHC Class I Expression for Tumor Growth and Metastasis
The very early work on transplantation of murine tumors and “tumor rejection antigens” by pioneers such as Tyzzer, Little and Snell lead 50 years ago to the discovery of the major histocompatibility antigens. In the present overview it is discussed that MHC class I antigens induce not only the rejection of tumors in allogeneic hosts but that they are also fundamental for the rejection of tumors and metastasis in syngeneic hosts. The studies demonstrate that for induction of a specific T cell response the tumor cells have to express not only a novel tumor associated antigen but also MHC class I antigens. Numerous reports have demonstrated strong variations in the expression of class I antigens on mouse and rat tumors, e.g. on thymomas (Schmidt et al., 1979), on spontaneous lung carcinomas (Eisenbach et al., 1983), on methyl-cholantrene A induced fibrosarcomas (De Baetselier et al., 1980; Hämmerling et al., 1987), cells transformed with human adenovirus strain 12 (Bernards et al., 1983), etc.. On many human tumors variable expression of HLA antigens was also observed (see Table 4). Because cytotoxic T cells can recognize foreign antigens only in conjunction with MHC class I structures the decreased class I expression on tumors was interpreted to facilitate the escape from immune surveillance. However, all these assumptions were based on indirect evidence, namely on a correlation between the absence of class I antigens and the tumorigenic properties of the tumor cells.
KeywordsTumor Rejection Antigen Mediate Lysis Major Histocompatibility Antigen Allogeneic Host Allele Specific Antibody
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