The @entity842 radical scavenger XXXX reduces the immunosuppressive activity of myeloid-derived suppressor cells and potentiates the antitumor activity of adoptive cytotoxic T lymphocyte immunotherapy.

@entity5 @entity19 @entity6706 @entity842 @entity320
UNASSIGNED: Adoptive immunotherapy with cytotoxic T lymphocytes (CTLs) can result in robust and durable antitumor responses. @entity5 -infiltrating CTLs produce IFNy and mediate antitumor activity, but they simultaneously induce counter-regulatory immunosuppressive mechanisms in the @entity5 by recruiting monocytic myeloid-derived suppressor cells (MDSCs) that limit their proliferation and effector function. Using a @entity19 model of adoptive immunotherapy for B16 @entity320 , we developed a strategy to augment CTL activity by downregulating immunosuppression by MDSCs. Intravenous injection of transgenic pmel-1 CTLs into @entity5 -bearing @entity19 , resulted in their infiltration into the @entity5 , but this was accompanied by the accumulation of large numbers of monocytic MDSCs (M-MDSCs). These cells hampered CTL function and reduced their numbers in the @entity5 . We determined that one mechanism responsible for this immunosuppression was the production of @entity842 (NO) by MDSCs in the @entity5 . Therefore, @entity19 were given the NO scavenger @entity6706 ( @entity6706 ) on the day after CTL transfer. This led to the restoration of impaired proliferative capacity and function of the CTLs, resulting in sustained suppression of @entity5 growth. Thus, we conclude that CTL therapy can be improved by counter-acting immunosuppression. Targeting NO, one mediator of the immunosuppressive activity of M-MDSCs, may be an appropriate strategy to restore impaired CTL function and improve the efficacy of immunotherapy.
