Tumor mechanisms of resistance to immune attack.

Abstract

The immune system plays a key role in the interactions between host and tumor. Immune selection pressure is a driving force behind the sculpting and evolution of malignant cancer cells to escape this immune attack. Several common tumor cell-based mechanisms of resistance to immune attack have been identified and can be broadly categorized into three main classes: loss of antigenicity, loss of immunogenicity, and creation of an immunosuppressive microenvironment. In this review, we will discuss in detail the relevant literature associated with each class of resistance and will describe the relevance of these mechanisms to human cancer patients. To conclude, we will outline the implications these mechanisms have for the treatment of cancer using currently available therapeutic approaches. Immunotherapy has been a successful addition to current treatment approaches, but many patients either do not respond or quickly become resistant. This reflects the ability of tumors to continue to adapt to immune selection pressure at all stages of development. Additional study of immune escape mechanisms and immunotherapy resistance mechanisms will be needed to inform future treatment approaches.