Evasion Of Immune Responses By Tumors

Many cancers develop mechanisms that allow them to evade anti-tumor immune responses. These mechanisms can broadly be divided into those that are intrinsic to the tumor cells and those that are mediated by other cells (Fig. 17-5). A major focus of tumor immunology is to understand the immune evasion mechanisms of tumors, with the hope that interventions to prevent immune evasion will increase the immunogenicity of tumors and maximize the responses of the host. Experimental evidence in mouse models indicates that immune responses to tumor cells impart selective pressures that result in the survival and outgrowth of variant tumor cells with reduced immunogenicity, a process that has been called tumor editing. For example, when tumors are induced by carcinogen treatment in either immunodeficient or immunocompetent mice and the tumors are then transplanted into new immunocompetent mice, the tumors that were derived from the immunodeficient mice are more frequently rejected by the recipient animal's immune system than are the tumors derived from the immunocompetent mice. This result indicates that tumors developing in the setting of a normal immune system become less immunogenic over time, which is consistent with selection of less immunogenic variant cells. Tumor immunoediting is thought to underlie the emergence of tumors that "escape" immune surveillance. We will now discuss the intrinsic and extrinsic tumor mechanisms that may underlie editing and escape.

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