Courtesy Jean-Robert Brisson NRC Inst. Biological Sciences
CD8+ T-cell tolerance of tumors can block an aggressive immune response against cancer and may diminish the efficacy of therapeutic vaccines. But Yiping Yang, a Duke University immunologist, says he and his colleagues have found a way to overcome T-cell tolerance using the immune system's innate response to pathogens. Membrane-bound Toll-like receptors (TLRs) detect repetitive epitopes commonly found in pathogens. Activating these receptors can influence adaptive responses, including T cell-mediated immunity.
The team reactivated tolerant T cells in mice by providing continuous TLR signals from viral vectors containing tumor antigens, and then inoculated mice with lymphoma cells. Ninety percent of the viral vector-treated mice survived after 15 weeks, compared to only 10% of those that had received just dendritic cell vaccine. But, Yvonne Paterson, professor of microbiology at the University of Pennsylvania, says that live vectors might trigger unfavorable immune responses.