The role of induced immune pressure

Encyclopedia of Cancer. Springer-Verlag (2014)

The editing of tumors in response to immune pressure is exacerbated when the immune system has been specifically primed to a tumor-associated antigen. In a mouse model for breast cancer in which HER-2/neu, a member of the epidermal growth factor receptor family, is overexpressed on breast tissue, resulting in the emergence of breast tumors, it was shown that mice immunized with cancer vaccines expressing fragments of HER-2/neu could control tumor outgrowth for a significant length of time but eventually succumbed. When HER-2/neu was isolated from the emerging tumors, they were found to have accumulated a significant number of mutations in the precise region of the molecule the particular vaccine targeted. In addition, it was verified for one of the fragments that each mutation occurred in a region recognized by CTLs and that this mutation abrogated CTL recognition. This is a clear demonstration of how the host immune system can sculpt a tumor-associated antigen to evade the immune system. Transplanted, syngeneic mouse tumors have also been shown to mutate in a region of an antigen expressed by the tumor and recognized by CTLs after adoptive transfer of T cells that recognize that region.


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