PD-1 expression marks activated T cells susceptible to PD-1–mediated inhibition but not whether a PD-1–mediated signal is being delivered. Molecular predictors of response to PD-1 immune checkpoint blockade (ICB) are needed. We describe a monoclonal antibody (mAb) that detects PD-1 signaling through the detection of phosphorylation of the immunotyrosine switch motif (ITSM) in the intracellular tail of mouse and human PD-1 (phospho–PD-1). We showed PD-1+ tumor-infiltrating lymphocytes (TILs) in MC38 murine tumors had high phosphorylated PD-1, particularly in PD-1+TIM-3+ TILs. Upon PD-1 blockade, PD-1 phosphorylation was decreased in CD8+ TILs. Phospho–PD-1 increased in T cells from healthy human donors after PD-1 engagement and decreased in patients with Hodgkin lymphoma following ICB. These data demonstrate that phosphorylation of the ITSM motif of PD-1 marks dysfunctional T cells that may be rescued with PD-1 blockade. Detection of phospho–PD-1 in TILs is a potential biomarker for PD-1 immunotherapy responses.
- Award ID(s):
- 1653782
- NSF-PAR ID:
- 10082879
- Date Published:
- Journal Name:
- Cell Reports
- Volume:
- 24
- Issue:
- 2
- ISSN:
- 2211-1247
- Page Range / eLocation ID:
- 379 to 390.e6
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1016/j.celrep.2018.06.054
