Minimal PD-1 expression in mouse and human NK cells under diverse conditions
- 31 May 2020
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
- Vol. 130 (6), 3051-3068
- https://doi.org/10.1172/JCI33353
Abstract
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 NI< 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.Keywords
Funding Information
- NIH, Robert Lambert Family Fund, NCI (HL140921,HL56067,AU34494,CA065493,CA224166-01,P30 CA093373,S10 OD018223,S10 RR 026825)
This publication has 71 references indexed in Scilit:
- Human NK Cells Selective Targeting of Colon Cancer–Initiating Cells: A Role for Natural Cytotoxicity Receptors and MHC Class I MoleculesThe Journal of Immunology, 2013
- Cellular and molecular basis of haploidentical hematopoietic stem cell transplantation in the successful treatment of high-risk leukemias: role of alloreactive NK cellsFrontiers in Immunology, 2013
- PD-1 is a novel regulator of human B-cell activationInternational Immunology, 2012
- Membrane-Bound IL-21 Promotes Sustained Ex Vivo Proliferation of Human Natural Killer CellsPLOS ONE, 2012
- Expansion, Purification, and Functional Assessment of Human Peripheral Blood NK CellsJournal of Visualized Experiments, 2011
- The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti–PD-1 antibodyBlood, 2010
- Cytotoxicity of Activated Natural Killer Cells against Pediatric Solid TumorsClinical Cancer Research, 2010
- Differential Regulation of GM1 and Asialo-GM1 Expression by T Cells and Natural Killer (NK) Cells in Respiratory Syncytial Virus InfectionViral Immunology, 2008
- Trogocytosis-based generation of suppressive NK cellsThe EMBO Journal, 2007
- Successful adoptive transfer and in vivo expansion of human haploidentical NK cells in patients with cancerBlood, 2005