Peripheral T cell receptor diversity is associated with clinical outcomes following ipilimumab treatment in XXXX .

@entity1 @entity5 @entity3794 @entity320
BACKGROUND: Ipilimumab improves overall survival in a subset of @entity1 with @entity320 . Peripheral blood T cell receptor (TCR) repertoire diversity has been associated with favorable outcomes in @entity1 with @entity5 , but its relevance as a biomarker for ipilimumab outcomes remains unknown. FINDINGS: In this pilot study, we analyzed the pre-treatment peripheral blood TCR repertoire in 12 @entity1 with @entity320 who received ipilimumab at 3  mg/kg (clinical benefit, n   =   4; no clinical benefit, n   =   8). TCR diversity was evaluated using a polymerase chain reaction assay which measures TCR combinatorial diversity between V and J genes from genomic DNA. TCR repertoire diversity was studied through @entity3794 (observed V-J rearrangements) and evenness (similarity between the frequencies of specific V-J rearrangements). The Wilcoxon rank sum test was used to compare @entity1 with clinical benefit and those without. Association with benefit in a dichotomized analysis was assessed through a Fisher's exact test. Overall survival was studied through log-rank analysis. There was a significant difference in @entity3794 (p   =   0.033) and evenness (p   =   0.028) between @entity1 with and without clinical benefit. Dichotomized analysis showed that none of the @entity1 with low @entity3794 (n   =   0/5, p   =   0.081) nor low evenness (n   =   0/7, p   =   0.01) achieved clinical benefit. There were no significant differences in overall survival. CONCLUSIONS: In this small group of @entity1 , baseline TCR diversity in the peripheral blood was associated with clinical outcomes. Further investigation is ongoing in larger cohorts of @entity1 to explore these preliminary findings and determine whether TCR diversity can be used as a predictive biomarker in @entity5 immunotherapy.
