Treating retroviral immunodeficiency-associated tumor by CD8 adoptive T-cell therapy (105.29)

Abstract

Abstract LP-BM5 virus infection in susceptible B6 mice induces a HIV-like immunodeficiency syndrome, termed “murine acquired immunodeficiency syndrome (MAIDS)”. We have previously shown that highly active, LP-BM5-specific CD8 cytolytic T lymphocytes (CTLs) can be raised against LP-BM5-associated B-cell lymphomas through in vivo priming and in vitro restimulation with syngeneic LP-BM5-associated B-cell lymphoma line. Adoptive transfer of such polyclonal anti-LP-BM5 tumor CTLs inhibited the development of MAIDS. To identify new potential immunotherapeutic approaches to promote protective CTL-mediated responses, thus to treat LP-BM5-associated B-cell lymphomas, we examined the effects of specific blockadge of the PD-1 mediated negative signaling pathway in CD8 T cells following tomor inoculation. Adoptive transfer experiments using CD8 T cells from B6.PD-1-/- mice were performed, and then tumor growth, and retrovirus-induced tumor specific effector CD8 T-cell responses were measured. Our results showed that LP-BM5-specific CTL responses were significantly enhanced in mice adoptively transferred with PD-1-/- CD8 T cells than that in miced transferred with wild type CD8 T cells. Tumor growth was also significantly inhibited in mice transferred with PD-1-/- CD8 T cells. Altogether, manipulation of PD-1-associated down-regulation of CD8 T cell responses may provide novel immunotherapies in treating retroviral infection-associated lyphomas.