Open AccessMonitoring PD-1 Phosphorylation to Evaluate PD-1 Signaling during Antitumor Immune Responses
Author(s) -
Xia Bu,
Vikram R. Juneja,
Carol Reynolds,
Kathleen M. Mahoney,
Melissa T. Bu,
Kathleen A. McGuire,
Seth Maleri,
Peng Hua,
Baogong Zhu,
Sarah R. Klein,
Edward Greenfield,
Philippe Armand,
Jérôme Ritz,
Arlene H. Sharpe,
Gordon J. Freeman
Publication year - 2021
Publication title -
cancer immunology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.976
H-Index - 87
eISSN - 2326-6074
pISSN - 2326-6066
DOI - 10.1158/2326-6066.cir-21-0493
Subject(s) - pd l1 , phosphorylation , immunotherapy , cancer research , blockade , immune system , immune checkpoint , cancer immunotherapy , monoclonal antibody , signal transduction , tumor infiltrating lymphocytes , immunology , medicine , biology , antibody , microbiology and biotechnology , receptor
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.