Rescue of exhausted CD8 T cells by PD-1–targeted therapies is CD28-dependent

Programmed cell death-1 (PD-1)-targeted therapies enhance T cell responses and show efficacy in multiple cancers, but the role of costimulatory molecules in this T cell rescue remains elusive. Here, we demonstrate that the CD28/B7 costimulatory pathway is essential for effective PD-1 therapy during chronic viral infection. Conditional gene deletion showed a cell-intrinsic requirement of CD28 for CD8 T cell proliferation after PD-1 blockade. B7-costimulation was also necessary for effective PD-1 therapy in tumor-bearing mice. In addition, we found that CD8 T cells proliferating in blood after PD-1 therapy of lung cancer patients were predominantly CD28-positive. Taken together, these data demonstrate…

• M
  Merck

  Awards: award296711, 52507
• NI
  National Institutes of Health

  Awards: AI30048,AI080192,AI056299,AI054456,AI089955,CA72669,AI037691, award296710