Impact of checkpoint blockade on cancer vaccine-activated CD8+ T cell responses

J Exp Med. 2020 Jul 6;217(7):e20191369. doi: 10.1084/jem.20191369.


Immune and molecular profiling of CD8 T cells of patients receiving DC vaccines expressing three full-length melanoma antigens (MAs) was performed. Antigen expression levels in DCs had no significant impact on T cell or clinical responses. Patients who received checkpoint blockade before DC vaccination had higher baseline MA-specific CD8 T cell responses but no evidence for improved functional responses to the vaccine. Patients who showed the best clinical responses had low PD-1 expression on MA-specific T cells before and after DC vaccination; however, blockade of PD-1 during antigen presentation by DC had minimal functional impact on PD-1high MA-specific T cells. Gene and protein expression analyses in lymphocytes and tumor samples identified critical immunoregulatory pathways, including CTLA-4 and PD-1. High immune checkpoint gene expression networks correlated with inferior clinical outcomes. Soluble serum PD-L2 showed suggestive positive association with improved outcome. These findings show that checkpoint molecular pathways are critical for vaccine outcomes and suggest specific sequencing of vaccine combinations.

Publication types

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

MeSH terms

  • Antigens, Neoplasm / metabolism
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology*
  • CTLA-4 Antigen / metabolism
  • Cancer Vaccines / immunology*
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Disease-Free Survival
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology*
  • Interferon-gamma / metabolism
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology*
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • MART-1 Antigen / metabolism
  • Melanoma / blood
  • Melanoma / genetics
  • Melanoma / immunology
  • Melanoma / pathology
  • Programmed Cell Death 1 Receptor / metabolism
  • Vaccination


  • Antigens, Neoplasm
  • CTLA-4 Antigen
  • Cancer Vaccines
  • Immune Checkpoint Inhibitors
  • MART-1 Antigen
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Interferon-gamma