Inflammation induced PD-L1-specific T cells

Authors:

Shamaila Munir1, Mia Thorup Lundsager1, Mia Aabroe Jørgensen1, Morten Hansen1, Trine Hilkjær Petersen2, Charlotte Menne Bonefeld2, Christina Friese1, Özcan Met1,2, Per thor Straten1,2 and Mads Hald Andersen1,2,3
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Affiliations:

1 National Center for Cancer Immune Therapy (CCIT-dk), Copenhagen University Hospital, Herlev, Denmark.

2 The LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.

3 IO Biotech ApS, DK-2200 Copenhagen, Denmark.

Keywords: 

PD-L1, T-cell immunity, Inflammation, IFN-γ, anti-Tregs, anti-regulatory T-cells.

Abbreviations:

DMSO – dimethylsulfoxide,

DNFB – 2,4-dinitrofluorobenzen,

dNL – draining lymph node,

HLA – human leukocyte antigen,

IFN – interferon,

i.p. – intra peritoneal,

OAA – olive oil:acetone mixture,

PBMC – peripheral blood mononuclear cell,

Treg – regulatory T cell.

Corresponding Author(s):

Mads Hald Andersen, National Center for Cancer Immune Therapy (CCIT-dk), Copenhagen University Hospital, Herlev, DK-2730 Herlev, Denmark; Phone: +45 38682602; Fax: +45 44530176; mads.hald.andersen@regionh.dk

Conflict of interest statement:

Mads Hald Andersen has filed several patent applica-tions based on the use of PD-L1 for vaccination. The rights of the patent applications have been transferred to Copenhagen University Hospital, Herlev, according to the Danish Law of Public Inventions at Public Research Institutions. The capital region has licensed these patents to the company IO Biotech ApS. MHA is a shareholder and board member of the IO Biotech ApS. The other authors declare “no conflict of interest”.

Please cite this article as:

Shamaila Munir, Mia Thorup Lundsager, Mia Aabroe Jørgensen, Morten Hansen, Trine Hilkjær Petersen, Charlotte Menne Bone-feld, Christina Friese, Özcan Met, Per thor Straten and Mads Hald Andersen (2019). Inflammation induced PD-L1-specific T cells. Cell Stress 3(10): 319-327. doi: 10.15698/cst2019.10.201

© 2019 Munir et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduc-tion in any medium, provided the original author and source are acknowledged.

Abstract:

PD-L1-specific T cells are a natural part of the T-cell repertoire in humans. Hence, we have previously described spontaneous CD8+ and CD4+ T-cell reactivity against PD-L1 in the peripheral blood of patients with various cancers as well as in healthy donors. It is well described that the expression of the PD-L1 protein is introduced in cells by pro-inflammatory cytokines, e.g. IFN-γ. In the current study, we were able to directly link inflammation with PD-L1-specific T cells by showing that inflammatory mediators such as IFN-γ generate measurable numbers of PD-L1-specific T cells in human PBMCs as well as in in vivo models. These PD-L1-specific T cells can vigorously modulate the cell compartments of the local environment. PD-L1-specific T cells may be important for immune homeostasis by sustaining the ongoing inflammatory response by the suppression of regulatory cell function both directly and indirectly.