First Author | Judge SJ | Year | 2020 |
Journal | J Clin Invest | Volume | 130 |
Issue | 6 | Pages | 3051-3068 |
PubMed ID | 32134744 | Mgi Jnum | J:329656 |
Mgi Id | MGI:6754853 | Doi | 10.1172/JCI133353 |
Citation | Judge SJ, et al. (2020) Minimal PD-1 expression in mouse and human NK cells under diverse conditions. J Clin Invest 130(6):3051-3068 |
abstractText | 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. |