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Author Notes:

For a complete list of authors, please see the full work.

Correspondence to: rahmed@emory.edu

We thank Mandy Ford (Emory University) for reagents, and Evgeniy Eruslanov (University of Pennsylvania School of Medicine) for experimental advice.

RA, DLB, GJF and AHS are inventors on patent numbers US 8552154 B2, US 8652465 B2, and US 9102727 B2, held by Emory University (Atlanta), Dana-Farber Cancer Institute (Boston), Brigham and Women’s Hospital (Boston) and Harvard University (Cambridge), that cover the topic of PD-1 directed immunotherapy.

Subjects:

Research Funding:

This work was supported by Merck pre-clinical grant 52507 (RA and AOK), and the National Institutes of Health grants R01 AI30048 (RA), P01 AI080192 (RA and GJF), P01 AI056299 (AHS, RA, GJF and BRB), P01 AI054456 (AHS), R01 AI089955 (GJF), R01 CA72669 (BRB), R01 AI037691 (LAT and RZ).

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • Science & Technology - Other Topics
  • CHRONIC VIRAL-INFECTION
  • RESPONSES
  • IMMUNITY
  • CANCER
  • PD-1
  • COSTIMULATION
  • BLOCKADE
  • EFFECTOR
  • MEMORY

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

Tools:

Journal Title:

Science

Volume:

Volume 355, Number 6332

Publisher:

, Pages 1423-1427

Type of Work:

Article | Post-print: After Peer Review

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 of mice. 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 CD28/B7 pathway in PD-1 therapy of cancer patients.

Copyright information:

© 2017 American Association for the Advancement of Science. All rights Reserved.

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