2013, pp 3-15
Date: 19 Sep 2012

Historical Perspectives and Current Trends in Cancer Immunotherapy

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Abstract

The immune system is exquisitely able to identify trace antigens and eliminate cells expressing them. Tumors are quintessentially antigenic tissues as a result of their many genetic mutations. This antigenicity, however, does not generally translate into useful immunogenicity as spontaneous rejection of clinically apparent tumors is rare. Early work in tumor immunology identified tumor-specific and tumor-associated antigens and formulated strategies to bolster antitumor immunity using paradigms arising from prior successes in understanding anti-pathogen immunity. It is now clear that the inability of endogenous immune mechanisms to eradicate clinically evident cancers owes in part to tumor-driven immune dysfunction, in part to the coevolution of antitumor immunity with the ever-changing antigens of the ever-mutating tumors (immunoediting) and to the fact that antitumor immunity is a form of autoimmunity. These newer understandings caused thinking to evolve and advance. Our rapidly increasing understanding of antitumor immunity and how it can be thwarted has led to new approaches to tumor immunotherapy with great promise to be much more successful than prior generations of approaches. This chapter discusses the evolution in thinking about tumor immunity, why endogenous antitumor immunity often fails after tumors become clinically apparent and why prior tumor immunotherapy approaches have generally had only modest success at best. New paradigms leading the field and the novel therapeutic approaches based on recent insights will be introduced.