Immunotherapy in preneoplastic disease: targeting early procarcinogenic inflammatory changes that lead to immune suppression and tumor tolerance.

Recent advances in immunotherapy have demonstrated that single agent vaccines can be effective when given as primary prevention before exposure to the causative agent, and partially effective in some patients with existing cancer. However, as tumors develop and progress, tumor-induced immune suppression and tolerance present the greatest barrier to therapeutic success. Preneoplastic disease represents an important opportunity to intervene with tumor antigen-targeted vaccines before these mechanisms of immune evasion outpace efforts by the immune system to destroy precancerous cells. However, as we discuss in this review, emerging evidence suggests that procarcinogenic inflammatory changes occur early in cancer development, in both patients and mouse models of cancer progression. Defining early inhibitory signals within tumor microenvironments will yield insights that can eventually be used in the clinic to target these events and deliver treatments that can be used in addition to cancer vaccines to prevent premalignant and early invasive cancers.