signature=c2481d075472cc13b5ff238deabb54d2,Signatures Associated with Rejection or Recurrence in HER...

摘要：

We have previously shown T--mediated rejection of the neu-overexpressing (MMC) in wild-type FVB . However, following rejection of , a fraction of experienced a recurrence of a neu antigen-negative variant (ANV) of MMC (evasion model) after a long latency period. In the present study, we determined that T derived from wild-type FVB can specifically recognize MMC by secreting and can induce apoptosis of MMC in vitro. Neu transgenic (FVBN202) develop spontaneous and cannot reject it (tolerance model). To dissect the mechanisms associated with rejection or tolerance of MMC , we compared transcriptional patterns within the microenvironment of MMC undergoing rejection with those that resisted it either because of evasion/antigen loss recurrence (ANV ) or because of intrinsic tolerance mechanisms displayed by the . Gene profiling confirmed that immune rejection is primarily mediated through activation of -stimulated genes and T-effector mechanisms. The evasion model showed combined activation of and Th2 with a deviation toward Th2 and that failed to achieve rejection likely because of lack of target antigen. Interestingly, the tolerance model instead displayed pathways through activation of regulatory mechanisms that included in particular the overexpression of (), receptor, and ()-1 and . These data provide a road map for the identification of novel biomarkers of immune responsiveness in clinical trials.

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