title: Peripheral T cell receptor diversity is associated with clinical outcomes following ipilimumab treatment in metastatic melanoma.
abstract: BACKGROUND
  Ipilimumab improves overall survival in a subset of patients with metastatic melanoma. Peripheral blood T cell receptor (TCR) repertoire diversity has been associated with favorable outcomes in patients with cancer, but its relevance as a biomarker for ipilimumab outcomes remains unknown.
  
  
  RESULTS
  In this pilot study, we analyzed the pre-treatment peripheral blood TCR repertoire in 12 patients with metastatic melanoma 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 richness (observed V-J rearrangements) and evenness (similarity between the frequencies of specific V-J rearrangements). The Wilcoxon rank sum test was used to compare patients 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 richness (p = 0.033) and evenness (p = 0.028) between patients with and without clinical benefit. Dichotomized analysis showed that none of the patients with low richness (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 patients, baseline TCR diversity in the peripheral blood was associated with clinical outcomes. Further investigation is ongoing in larger cohorts of patients to explore these preliminary findings and determine whether TCR diversity can be used as a predictive biomarker in cancer immunotherapy.
authors.affiliation: Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 USA ; Weill Cornell Medical College, 525 E 68th Street, New York, 10065 USA ; Assistant Attending Physician, Melanoma and Immunotherapeutics Oncology Service, Memorial Sloan Kettering Cancer Center, 1300 East 66th Street, New York, NY 10065 USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Postow
authors.affiliation: ImmunID, Grenoble, France.
authors.forename: Manuarii
authors.initials: M
authors.lastname: Manuel
authors.affiliation: Immune Monitoring Core Facility, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York City, NY 10065 USA.
authors.forename: Phillip
authors.initials: P
authors.lastname: Wong
authors.affiliation: Immune Monitoring Core Facility, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York City, NY 10065 USA.
authors.forename: Jianda
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Immune Monitoring Core Facility, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York City, NY 10065 USA.
authors.forename: Zhiwan
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Immune Monitoring Core Facility, Ludwig Center for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York City, NY 10065 USA.
authors.forename: Cailian
authors.initials: C
authors.lastname: Liu
authors.affiliation: ImmunID, Grenoble, France.
authors.forename: Solène
authors.initials: S
authors.lastname: Perez
authors.affiliation: ImmunID, Grenoble, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tanneau
authors.affiliation: ImmunID, Grenoble, France.
authors.forename: Marlène
authors.initials: M
authors.lastname: Noel
authors.affiliation: ImmunID, Grenoble, France.
authors.forename: Anaïs
authors.initials: A
authors.lastname: Courtier
authors.affiliation: ImmunID, Grenoble, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pasqual
authors.affiliation: Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 USA ; Weill Cornell Medical College, 525 E 68th Street, New York, 10065 USA.
authors.forename: Jedd D
authors.initials: JD
authors.lastname: Wolchok