51 - Immunotherapy

Summary

CANCER IMMUNOBIOLOGY

Tumors Are Recognized by the Immune System

The idea of fighting tumors with immunological weapons has been pursued empirically in modern medicine since the end of the nineteenth century. The birth of modern tumor immunology is usually credited to experiments in the 1940s and 1950s showing that inbred mice are protected by exposure to harmless tumor components (vaccination) from the growth of a subsequent inoculum of live tumor cells (challenge) (Gross 1943; Foley 1953; Prehn and Main 1957; Klein et al. 1960). Countless vaccination-challenge experiments were performed over the subsequent decades to dissect immune mechanisms that protect the vaccinated host, using either immunocompetent or immunodepressed hosts. The overall results are quite clear; however, they form the basis of a contradiction between preclinical and clinical tumor immunology that must be taken into account to understand current and future therapeutic developments.

Innate immunity is fundamental, both because its cells and molecules (e.g., phagocytes and interferons) directly attack tumors and because antigen presentation (dendritic and other cells) is required for the generation of adaptive immunity (Restifo and Wunderlich 2005). Myeloid-derived suppressor cells (MDSCs) play a negative role and inhibit antitumor immunity (Nagaraj and Gabrilovich 2008; Marigo et al. 2008). Natural killer (NK) cells are highly active against circulating tumor cells; hence they play a significant antimetastatic role: without NK cells, the experimental metastatic ability of tumor cells can increase a hundredfold (Ljunggren and Malmberg 2007).