Combined TCR Repertoire Profiles and Blood Cell Phenotypes Predict Melanoma Patient Response to Personalized Neoantigen Therapy plus Anti-PD-1

Cell Rep Med. 2020 Nov 17;1(8):100141. doi: 10.1016/j.xcrm.2020.100141.


T cells use highly diverse receptors (TCRs) to identify tumor cells presenting neoantigens arising from genetic mutations and establish anti-tumor activity. Immunotherapy harnessing neoantigen-specific T cells to target tumors has emerged as a promising clinical approach. To assess whether a comprehensive peripheral mononuclear blood cell analysis predicts responses to a personalized neoantigen cancer vaccine combined with anti-PD-1 therapy, we characterize the TCR repertoires and T and B cell frequencies in 21 patients with metastatic melanoma who received this regimen. TCR-α/β-chain sequencing reveals that prolonged progression-free survival (PFS) is strongly associated with increased clonal baseline TCR repertoires and longitudinal repertoire stability. Furthermore, the frequencies of antigen-experienced T and B cells in the peripheral blood correlate with repertoire characteristics. Analysis of these baseline immune features enables prediction of PFS following treatment. This method offers a pragmatic clinical approach to assess patients' immune state and to direct therapeutic decision making.

Trial registration: NCT02897765.

Keywords: NEO-PV-01; T cell clonality; TCR repertoire; anti-PD-1; cancer vaccines; flow cytometry; immunotherapy; melanoma; predictive biomarkers.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / immunology*
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Blood Cells / pathology*
  • Cancer Vaccines / immunology
  • Cell Line
  • Cell Line, Tumor
  • Female
  • HEK293 Cells
  • Humans
  • Immunotherapy / methods
  • Jurkat Cells
  • Longitudinal Studies
  • Male
  • Melanoma / drug therapy*
  • Melanoma / immunology*
  • Melanoma / pathology
  • Phenotype
  • Programmed Cell Death 1 Receptor / immunology*
  • Progression-Free Survival
  • Receptors, Antigen, T-Cell, alpha-beta / immunology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology


  • Antigens, Neoplasm
  • Cancer Vaccines
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, Antigen, T-Cell, alpha-beta

Associated data