Moving Immunoprevention Beyond Virally Mediated Malignancies: Do We Need to Link It to Early Detection?

Vaccines can successfully prevent viral infections and have emerged as an effective strategy for preventing some virally mediated malignancies. They also represent our major hope for cost-effective reduction of the cancer burden. The concept that the immune system mediates surveillance and editing roles against tumors is now well-established in murine models. However, harnessing the immune system to prevent human cancers that do not have a known viral etiology has not yet been realized. Most human cancers originate in a premalignant phase that is more common than the cancer itself. Many of the genetic changes that underlie carcinogenesis originate at this stage when the malignant phenotype is not manifest. Studies evaluating host response in human premalignancy have documented that these lesions are immunogenic, setting the stage for immune-based approaches for targeted prevention of human cancer. However, recent studies suggest that the hierarchy of T cell exhaustion and immune-suppressive factors have already begun to emerge in many preneoplastic states. These considerations underscore the need to link immune prevention to earlier detection of such lesions and to personalize such approaches based on the status of the pre-existing immune response.