Content area
Full Text
REVIEW
Cancer immunotherapy attempts to harness the exquisite power and specificity of the immune system for the treatment of malignancy. Although cancer cells are less immunogenic than pathogens, the immune system is clearly capable of recognizing and eliminating tumor cells. However, tumors frequently interfere with the development and function of immune responses. Thus, the challenge for immunotherapy is to use advances in cellular and molecular immunology to develop strategies that effectively and safely augment antitumor responses.
Ambrose Bierce's cynical description of the evolving field of medicine as "a stone flung down the Bowery to kill a dog on Broadway" often aptly describes conventional cancer therapies. By contrast, the immune system has evolved strategies, largely in response to infections, to efficiently search for and specifically destroy diseased targets. After nearly a century of debate as to whether the immune system can actually target tumors (1-3), compelling evidence now suggests that immune cells play an important role in the control of malignancy (4). This has first been implied by both occasional spontaneous regressions of cancers in immunocompetent hosts and increased cancer incidence in immunocompromised individuals. Second, tumor immunity can be demonstrated in experimental animal models. For example, mice with defined immunological defects exhibit greater susceptibility to spontaneous and induced tumors, with many of these tumors rejected if transplanted into normal hosts (4, 5). Third, the immune system often appears cognizant of tumors, as reflected by an accumulation of immune cells at tumor sites, which correlates with improved prognosis (6). Finally, with improved technologies, antitumor immune responses can now be detected directly from many patients. Augmenting these responses has started to yield therapeutic benefits not only in experimental models but also in cancer patients. Advances in cellular and molecular immunology in the past two decades have provided enormous insights into the nature and consequences of interactions between tumors and immune cells and continue to suggest strategies by which the immune system might be harnessed for therapy of established malignancies.
Cells of the innate immune system respond to "danger" signals, which can be provided by growing tumors as a consequence of the genotoxic stress of cell transformation and disruption of the surrounding microenvironment. Under ideal conditions, these signals will induce inflammation, activate innate effector cells with antitumor...