PD-1 expression on mouse intratumoral NK cells and its effects on NK cell phenotype
Arnika K. Wagner,
Nadir Kadri,
Chris Tibbitt,
Koen van de Ven,
Sunitha Bagawath-Singh,
Denys Oliinyk,
Eric LeGresley,
Nicole Campbell,
Stephanie Trittel,
Peggy Riese,
Ulf Ribacke,
Tatyana Sandalova,
Adnane Achour,
Klas Kärre,
Benedict J. Chambers
Affiliations
Arnika K. Wagner
Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden
Nadir Kadri
Science for Life Laboratory, Department of Medicine Solna, Karolinska Institute, and Division of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
Chris Tibbitt
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden
Koen van de Ven
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden; Centre for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
Sunitha Bagawath-Singh
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
Denys Oliinyk
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden
Eric LeGresley
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden
Nicole Campbell
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden
Stephanie Trittel
Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany
Peggy Riese
Department of Vaccinology and Applied Microbiology, Helmholtz Centre for Infection Research, Braunschweig, Germany
Ulf Ribacke
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
Tatyana Sandalova
Science for Life Laboratory, Department of Medicine Solna, Karolinska Institute, and Division of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
Adnane Achour
Science for Life Laboratory, Department of Medicine Solna, Karolinska Institute, and Division of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden
Klas Kärre
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
Benedict J. Chambers
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Huddinge, Stockholm, Sweden; Corresponding author
Summary: Although PD-1 was shown to be a hallmark of T cells exhaustion, controversial studies have been reported on the role of PD-1 on NK cells. Here, we found by flow cytometry and single cell RNA sequencing analysis that PD-1 can be expressed on MHC class I-deficient tumor-infiltrating NK cells in vivo. We also demonstrate distinct alterations in the phenotype of PD-1-deficient NK cells and a more mature phenotype which might reduce their capacity to migrate and kill in vivo. Tumor-infiltrating NK cells that express PD-1 were highly associated with the expression of CXCR6. Furthermore, our results demonstrate that PD-L1 molecules in membranes of PD-1-deficient NK cells migrate faster than in NK cells from wild-type mice, suggesting that PD-1 and PD-L1 form cis interactions with each other on NK cells. These data demonstrate that there may be a role for the PD-1/PD-L1 axis in tumor-infiltrating NK cells in vivo.