Rescue of exhausted CD8 T cells by PD-1–targeted therapies is CD28-dependent
Science, 2017•science.org
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 …
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 …
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 CD28-costimulation requirement for CD8 T cell rescue and suggest an important role for the CD28/B7 pathway in PD-1 therapy of cancer patients.
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