Minimal PD-1 expression in mouse and human NK cells under diverse conditions

Sean J. Judge, Cordelia Dunai, Ethan G. Aguilar, Sarah C. Vick, Ian R. Sturgill, Lam T. Khuat, Kevin M. Stoffel, Jonathan Van Dyke, Dan L. Longo, Morgan A. Darrow, Stephen K. Anderson, Bruce R. Blazar, Arta M. Monjazeb, Jonathan S. Serody, Robert J. Canter, William J. Murphy

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


PD-1 expression is a hallmark of both early antigen-specific T cell activation and later chronic stimulation, suggesting key roles in both naive T cell priming and memory T cell responses. Although significant similarities exist between T cells and NK cells, there are critical differences in their biology and functions reflecting their respective adaptive and innate immune effector functions. Expression of PD-1 on NK cells is controversial despite rapid incorporation into clinical cancer trials. Our objective was to stringently and comprehensively assess expression of PD-1 on both mouse and human NK cells under multiple conditions and using a variety of readouts. We evaluated NK cells from primary human tumor samples, after ex vivo culturing, and from multiple mouse tumor and viral models using flow cytometry, quantitative reverse-transcriptase PCR (qRT-PCR), and RNA-Seq for PD-1 expression. We demonstrate that, under multiple conditions, human and mouse NK cells consistently lack PD-1 expression despite the marked upregulation of other activation/regulatory markers, such as TIGIT. This was in marked contrast to T cells, which were far more prominent within all tumors and expressed PD-1. These data have important implications when attempting to discern NK from T cell effects and to determine whether PD-1 targeting can be expected to have direct effects on NK cell functions.

Original languageEnglish (US)
Pages (from-to)3051-3068
Number of pages18
JournalJournal of Clinical Investigation
Issue number6
StatePublished - Jun 1 2020

Bibliographical note

Funding Information:
This work was supported in part by NIH/NCI grant R01 HL140921 (to WJM); P50 CA058223 (to JSS); R01 HL56067, R37 AU34494, and 2P01 CA065493 (to BRB); and U01 CA224166-01 and the Robert Lambert Family Fund (to RJC). This work was also supported in part by funds from the UCD Comprehensive Cancer Center and the UCD Flow Cytometry Shared Resource Laboratory, with funding from NCI P30 CA093373 (Cancer Center), S10 OD018223 (Astrios Cell Sorter), and S10 RR 026825 (Fortes-sa Cytometer) grants, with technical assistance from Bridget McLaughlin and Jonathan Van Dyke. Specimens were provided by the UCD Pathology Biorepository, which is jointly funded by the UCD Comprehensive Cancer Support Grant (CCSG) awarded by the NCI (P30 CA093373) and the UCD Department of Pathology and Laboratory Medicine. We give special thanks to Wissam J. Halabi (UCD Division of Colorectal Surgery), Sepideh Gholami (UCD Division of Surgical Oncology), Andrew Birkeland (UCD Department of Otolaryngology), and the past and current members of the Murphy lab for helpful discussions.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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