Probing immune inflammation in premalignancy.

CS14-03

Preneoplastic growths of transformed cells are common and identify a population at risk for clinical cancer. Monoclonal gammopathy of undetermined significance (MGUS) represents a precursor lesion to myeloma. Recent studies have shown that tumor cells in preneoplastic gammopathy carry several of the cytogenetic changes initially observed in multiple myeloma, suggesting a role for additional events including those involving the host in controlling malignant transformation. These events are attractive targets for prevention of this incurable cancer. In recent studies, we have shown that the immune system is capable of recognizing MGUS tumors. T cells in the tumor bed in MGUS are enriched for preneoplasia specific effector T cells, which includes both CD4 and CD8+ T cells (J Exp Med 198:1753, 2003). Freshly isolated T cells from the myeloma tumor bed lack such effector function. Progressive myeloma is also associated with a loss of effector function of innate glycolipid reactive natural killer T cells (J Exp Med 197:1667, 2003). Together these data suggest that changes in the immune microenvironment may contribute to malignant transformation in myeloma. Current studies in our lab are focused on identifying and characterizing the nature and targets of this naturally occurring host response in patients with MGUS and early myeloma. Harnessing the naturally occurring host innate and adaptive immune response in preneoplastic states may be a powerful approach for targeted immune prevention of cancer.