UNASSIGNED: 2503 Background: The purpose of this retrospective study was to identify peripheral blood biomarkers associated with the therapeutic effect of ipilimumab, a human antibody against @entity4386 ( @entity4386 ). Immunophenotypic changes in @entity404 (+) and @entity405 (+) T cells from advanced @entity320 @entity1 treated with ipilimumab were identified by gene expression profiling and subsequently validated by flow cytometry Methods: @entity404 (+) and @entity405 (+) T cells were purified by flow cytometry sorting from peripheral blood pre- and post- ipilimumab treatment from stages IIIC/IV @entity320 @entity1 @entity66 on an adjuvant trial. Microarray analysis of purified @entity404 (+) and @entity405 (+) T cells to identify gene profiling changes induced by ipilimumab were performed in 18 @entity1 . Flow cytometry analysis of a larger, overlapping cohort of 36 @entity1 was performed to confirm effects on T cell phenotypes Results: Ipilimumab augmented total @entity404 (+) T cells and decreased @entity404 (+) and @entity405 (+) na  ve T cells. Mean fluorescence intensity (MFI) of proliferation marker Ki67, the @entity12448 ( @entity12448 ), and the polarizing regulatory molecule @entity9388 were significantly up-regulated on @entity404 (+) and @entity405 (+) T cells (p<0.01 Wilcoxon). Percent expression and MFI of @entity10807 in @entity405 (+) T cells was increased and @entity15636 (eomesodermin) was decreased on @entity405 + T cells (both p<0.04). The MFI of @entity9350 and @entity6978 on @entity404 (+) T cells was decreased (p<0.001). Increased expression of @entity12448 and Ki-67 in @entity405 (+) T cells were negatively associated with developing immune related adverse events (p=0.04, Wald), and increased @entity15636 on @entity405 + T cells was associated with shorter @entity4557 ( @entity4557 )(p=0.04). Higher baseline @entity15636 @entity405 + expression was predictive of favorable @entity4557 (p=0.03) Conclusions: Increased expression of proliferation and polarization markers in @entity404 (+) and @entity405 (+) cells, decreased @entity9350 and @entity6978 on @entity404 (+) T cells and up-regulated @entity10807 in @entity405 (+) T cells may serve as pharmacodynamic indicators of the effects of ipilimumab. Increased activation markers @entity12448 and @entity15636 were significantly associated with fewer adverse events and less favorable outcome, respectively, but baseline elevated expression of @entity15636 appears to predict favorable relapse-free survival in this analysis.

Pharmacodynamic and predictive markers of ipilimumab on @entity320 XXXX ' T-cells.

@entity1 :: ('9606', 'Species') :: ['patients'] @entity404 :: ('920', 'Gene') :: ['CD4'] @entity66 :: ('MESH:D004194', 'Disease') :: ['rendered free of disease'] @entity4557 :: ('MESH:D012008', 'Disease') :: ['relapse free-survival', 'RFS'] @entity9388 :: ('2625', 'Gene') :: ['GATA3'] @entity15636 :: ('8320', 'Gene') :: ['EOMES'] @entity10807 :: ('3002', 'Gene') :: ['Granzyme B'] @entity12448 :: ('29851', 'Gene') :: ['ICOS', 'Inducible T cell Co-Stimulator'] @entity6978 :: ('3575', 'Gene') :: ['IL-7R'] @entity4386 :: ('1493', 'Gene') :: ['cytotoxic T lymphocyte antigen-4', 'CTLA-4'] @entity9350 :: ('1236', 'Gene') :: ['CCR7'] @entity405 :: ('925', 'Gene') :: ['CD8'] @entity320 :: ('MESH:D008545', 'Disease') :: ['melanoma']
@entity1 :: (9606,Species) :: ['patients']
