@article {1051276,
	title = {Rescue of exhausted CD8 T cells by PD-1-targeted therapies is CD28-dependent},
	journal = {Science},
	volume = {355},
	number = {6332},
	year = {2017},
	month = {2017 Mar 31},
	pages = {1423-1427},
	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.



	PubMed\&nbsp;DOI

},
	issn = {1095-9203},
	doi = {10.1126/science.aaf0683},
	author = {Kamphorst, Alice O and Wieland, Andreas and Nasti, Tahseen and Yang, Shu and Zhang, Ruan and Barber, Daniel L and Konieczny, Bogumila T and Daugherty, Candace Z and Koenig, Lydia and Yu, Ke and Sica, Gabriel L and Sharpe, Arlene H and Freeman, Gordon J and Blazar, Bruce R and Turka, Laurence A and Owonikoko, Taofeek K and Pillai, Rathi N and Ramalingam, Suresh S and Araki, Koichi and Ahmed, Rafi}
}
