Selective Pressure and Tumor Escape

There is a wide variety of mechanisms that lead to the formation of tumor escape mutants [28]. The simplest form of tumor escape is via the loss of a tumor antigen expressed on a tumor cell. How the immune system applies selective pressure that leads to the formation of antigen-loss escape mutants is easily demonstrated in vitro. If cytotoxic T lymphocytes in cell cultures containing specific T cells plus tumor cells eliminate some, but not all of the tumor cells, then the tumor cells will undergo selective depletion. If the surviving tumor cells are allowed to proliferate and are re-exposed to another round of selection by T cells, and this process is repeated many times over a long period of time, the cell cultures will eventually develop escape mutant tumor cells that are completely resistant to elimination by the specific T cells [29]. The experiments of Dunn et al. [30] revealed that immune surveillance that fails to completely eliminate tumors provides this selective pressure for the development of escape mutations. It is believed that the inherent genetic instability of tumor cells induces random mutations in the proliferating tumor cells, and that specific T cells provide selective pressure for the survival of specific mutations that lead to immune escape. This selective T cell pressure is therefore an example of Darwinian natural selection at the cellular level. This mechanism of tumor escape has also been shown to occur in vivo in patients immunized against specific tumor antigens [31].

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