Lerrer et al. showed that unlike naive cells, TCM and TEM cells proliferated more when stimulated through TCR and PD-1 than through only TCR. PD-1 signaling regulated more than half of the TCR transcriptome to fine tune the response, and PD-L2 had more of an impact than PD-L1. Also, PD-1 ligation induced (or inhibited) genes independent of TCR signaling and differentially in T cell functional subsets; PD-L1 was more impactful. PD-L1 or PD-L2 treatment boosted TCR-induced STAT1 and STAT2 levels. Lower STAT1 and/or STAT2 T cell expression levels were associated with better checkpoint blockade response and overall survival in patients.
Contributed by Paula Hochman
ABSTRACT: Despite the obvious inhibitory outcome of PD-1 signaling, an additional series of functions are activated. We have observed that T cells stimulated through the T cell receptor (TCR) and PD-1 primarily do not proliferate; however, there is a population of cells that proliferates more than through TCR stimulation alone. In this study, we performed flow cytometry and RNA sequencing on individual populations of T cells and discovered that unlike naive T cells, which were inhibited following PD-1 ligation, T cells that proliferated more following PD-1 ligation were associated with effector and central memory phenotypes. We showed that these populations had different gene expression profiles following PD-1 ligation with PD-L1 compared to PD-L2. The presence of transcriptionally and functionally distinct T cell populations responsive to PD-1 ligation provides new insights into the biology of PD-1 and suggest the use of T cell subset-specific approaches to improve the clinical outcome of PD-1 blockade.
Author Info: (1) Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA. (2) Columbia Center for Translational Immunology, Columbia University
Author Info: (1) Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA. (2) Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA. Department of Genetics and Genomic Sciences, Ichan School of Medicine at Mount Sinai, New York, NY 10029, USA. (3) Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA. (4) Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA. (5) Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032, USA. Division of Rheumatology, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
