Defining the role of the immune system in cancer treatment: highlights from the Immunochemotherapy

. During the elimination phase, the immune system is able to destroy tumors before they become clinically detectable. At this stage, the innate immune sys-tem plays an important role. Using the carcino-gen methylcholanthrene to induce tumors in mice, he defined a new pathway of recognition by natural killer cells of stressed cells undergoing transformation, which is mediated by the surface molecule H2-M3. Interestingly, this molecule can be induced on tumor cells treated with some chemotherapy agents and ionizing radiation, sug-gesting that therapy could recover the ability of cells from established cancers to be recognized by natural killer cells. Neoplastic cells that escape the elimination phase progress to the equilibrium phase, dur-ing which the adaptive immune system prevents tumor outgrowth but cannot eliminate the tumor. The dynamic nature of the equilibrium established between host and immune system is highlighted by the fact that depletion of key lymphocytes, such as CD8 T cells, leads to rapid tumor progres-sion. Data by Smyth and colleagues suggest that immunosuppressive receptors on T cells (i.e., cyto-toxic T lymphocyte antigen [CTLA]-4 and pro-grammed death [PD]-1) limit their activity in this setting. He hypothesized that therapeutics target-ing these receptors, which are currently tested in advanced cancers, could also have a role in the prophylaxis of preclinical neoplastic conditions.