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

Alice O. Kamphorst, Andreas Wieland, Tahseen Nasti, Shu Yang, Ruan Zhang, Daniel L. Barber, Bogumila T. Konieczny, Candace Z. Daugherty, Lydia Koenig, Ke Yu, Gabriel L. Sica, Arlene H. Sharpe, Gordon J. Freeman, Bruce R. Blazar, Laurence A. Turka, Taofeek K. Owonikoko, Rathi N. Pillai, Suresh S. Ramalingam, Koichi Araki, Rafi Ahmed

Research output: Contribution to journalArticlepeer-review

482 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1423-1427
Number of pages5
JournalScience
Volume355
Issue number6332
DOIs
StatePublished - Mar 31 2017

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