Integrative molecular and clinical modeling of clinical outcomes to PD1 blockade in patients with metastatic melanoma

Abstract Immune-checkpoint blockade (ICB) has demonstrated efficacy in many tumor types, but predictors of responsiveness to anti-PD1 ICB are incompletely characterized. In this study, we analyzed a clinically annotated cohort of patients with melanoma ( n = 144) treated with anti-PD1 ICB, with whole-exome and whole-transcriptome sequencing of pre-treatment tumors. We found that tumor mutational burden as a predictor of response was confounded by melanoma subtype, whereas multiple novel genomic and transcriptomic features predicted selective response, including features associated with MHC-I and MHC-II antigen presentation. Furthermore, previous anti-CTLA4 ICB exposure was associated with different predictors…

• NS
  National Science Foundation

  Award: DGE1144152
• CC
  Conquer Cancer Foundation
• DR
  Damon Runyon Cancer Research Foundation
• DM
  Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
• DF
  Deutsche Forschungsgemeinschaft

  Awards: SCHA 422/17, HO 6389/2-1, 2376/1-1, 6389/2-1, KFO 337, SCHA 422/17-1, PA 2376/1-1
• UD
  Universität des Saarlandes
• NC
  Nationales Centrum für Tumorerkrankungen Heidelberg
• NI
  National Institutes of Health

  Awards: DGE1144152, GM008313, K08 CA234458, U01 CA233100, CA233100, R01 CA227388, T32 GM008313