Table 1

158 peripheral immune cell subsets analyzed by flow cytometry

1. Total CD4+ T cells 2. Total CD8+ T cells 4. Total B cells
PD-L1+ CD4 – activation/inhibitionPD-L1+ CD8 – activation/inhibitionPD-L1+ B cells – activation/inhibition
PD-1+ CD4 – activation/inhibitionPD-1+ CD8 – activation/inhibitionPD-1+ B cells- activation/inhibition
CTLA-4+ CD4 – inhibitionCTLA-4+ CD8 – inhibition 5. Total NK
Tim-3+ CD4 – inhibitionTim-3+ CD8 – inhibitionPD-L1+ NK – inhibition
41bb+ CD4 – costimulation41bb+ CD8 – costimulationPD-1+ NK – activation/inhibition
Ki67+ CD4 – proliferationKi67+ CD8 – proliferationTim-3+ NK – activation/inhibition
CD73+ CD4 – exhausted/suppressiveCD73+ CD8 – exhausted/suppressiveKi67+ NK – proliferation
ICOS+ CD4 – activationNaïve (CCR7+CD45RA+) CD8NKp30+ NK – activation
 ICOS+ PD-L1+ CD4 – activation/inhibitionCentral memory (CCR7+CD45RA-) CD8NKp46+ NK – activation
 ICOS+ PD-1+ CD4 – activation/inhibition PD-L1+ CM CD8 – activation/inhibitionNKG2D+ NK – activation
Naïve (CCR7+CD45RA+) CD4 PD-1+ CM CD8 – activation/inhibitionCD226+ NK – adhesion/activation
Central memory (CCR7+ CD45RA-) CD4 CTLA-4+ CM CD8 – inhibitionMature (CD16+ CD56dim) NK – lytic
 PD-L1+ CM CD4 – activation/inhibition Tim-3+ CM CD8 – inhibition PD-L1+ mature NK – inhibition
 PD-1+ CM CD4 – activation/inhibition 41bb+ CM CD8 – costimulation PD-1+ mature NK – activation/inhibition
 CTLA-4+ CM CD4 – inhibition Ki67+ CM CD8 – proliferation Tim-3+ mature NK – activation/inhibition
 Tim-3+ CM CD4 – inhibition CD73+ CM CD8 – exhausted/suppressive Ki67+ mature NK – proliferation
 41bb+ CM CD4 – costimulationEffector memory (CCR7- CD45RA-) CD8 NKp30+ mature NK – activation
 Ki67+ CM CD4 – proliferation PD-L1+ EM CD8 – activation/inhibition NKp46+ mature NK – activation
 CD73+ CM CD4 – exhausted/suppressive PD-1+ EM CD8 - activation/inhibition NKG2D+ mature NK – activation
Effector memory (CCR7- CD45RA-) CD4 CTLA-4+ EM CD8 – inhibition CD226+ mature NK – adhesion/activation
 PD-L1+ EM CD4 – activation/inhibition Tim-3+ EM CD8 – inhibitionFunctional intermediate (CD16+ CD56br) NK – lytic, cytokine production
 PD-1+ EM CD4 – activation/inhibition 41bb+ EM CD8 – costimulation PD-L1+ functional intermediate NK – inhibition
 CTLA-4+ EM CD4 – inhibition Ki67+ EM CD8 – proliferation PD-1+ functional intermediate NK – activation/inhibition
 Tim-3+ EM CD4 – inhibition CD73+ EM CD8 – exhausted/suppressive Tim-3+ functional intermediate NK – activation/inhibition
 41bb+ EM CD4 – costimulationEMRA (CCR7-CD45RA+) CD8 Ki67+ functional intermediate NK – proliferation
 Ki67+ EM CD4 – proliferation PD-L1+ EMRA CD8 – activation/inhibition NKp30+ functional intermediate NK – activation
 CD73+ EM CD4 – exhausted/suppressive PD-1+ EMRA CD8 – activation/inhibition NKp46+ functional intermediate NK – activation
EMRA (CCR7-CD45RA+) CD4 CTLA-4+ EMRA CD8 – inhibition NKG2D+ functional intermediate NK – activation
 PD-L1+ EMRA CD4 – activation/inhibition Tim-3+ EMRA CD8 – inhibition CD226+ functional intermediate NK – adhesion/activation
 PD-1+ EMRA CD4 – activation/inhibition 41bb+ EMRA CD8 – costimulationImmature (CD16- CD56br) NK – cytokine production
 CTLA-4+ EMRA CD4 – inhibition Ki67+ EMRA CD8 – proliferation PD-L1+ immature NK – inhibition
 Tim-3+ EMRA CD4 – inhibition CD73+ EMRA CD8 – exhausted/suppressive PD-1+ immature NK – activation/inhibition
 41bb+ EMRA CD4 – costimulation 3. Total Tregs  Tim-3+ immature NK – activation/inhibition
 Ki67+ EMRA CD4 – proliferationPD-L1+ Tregs – activation/inhibition Ki67+ immature NK – proliferation
 CD73+ EMRA CD4 – exhausted/suppressivePD-1+ Tregs – suppression NKp30+ immature NK – activation
CTLA-4+ Tregs – suppression NKp46+ immature NK – activation
ICOS+ Tregs – suppression NKG2D+ immature NK – activation
CD45RA+ Tregs – highly expandable in vitro CD226+ immature NK – adhesion/activation
CD49d- Tregs – suppression Unconventional (CD16- CD56dim) NK – non-lytic, non-cytokine production
Ki67+ Tregs – proliferation
CD38+ Tregs – suppression
HLA-DR+ Tregs – suppression
6. Total NK-T 9. Total MDSC 10. Total Monocytes
PD-L1+ NK-T – inhibitionPD-L1+ MDSC – inhibitionPD-L1+ monocytes – inhibition
PD-1+ NK-T – activation/inhibitionPD-1+ MDSC – activation/inhibitionPD-1+ monocytes – activation/inhibition
Tim-3+ NK-T – inhibitionCD16+ MDSC – immature/suppressionClassical monocytes – phagocytic
Ki67+ NK-T – proliferationMonocytic (CD14+ CD15-) MDSC PD-L1+ classical monocytes – inhibition
7. Total cDC  PD-L1+ mMDSC – inhibition PD-1+ classical monocytes- activation/inhibition
PD-L1+ cDC – inhibition PD-1+ mMDSC – activation/inhibitionIntermediate monocytes phagocytic/proinflammatory
PD-1+ cDC – activation/inhibition CD16+ mMDSC – immature/suppression PD-L1+ intermediate monocytes – inhibition
Tim-3+ cDC – inhibitionGranulocytic (CD14- CD15+) MDSC PD-1+ intermediate monocytes- activation/inhibition
Ki67+ cDC – proliferation PD-L1+ gMDSC – inhibitionNon-classical monocytes – proinflammatory
8. Total pDC  PD-1+ gMDSC – activation/inhibition PD-L1+ non-classical monocytes – inhibition
PD-L1+ pDC – inhibition CD16+ gMDSC – immature/suppression PD-1+ non-classical monocytes- activation/inhibition
PD-1+ pDC – activation/inhibition
Tim-3+ pDC – inhibition
Ki67+ pDC – proliferation
  • Ten parental phenotypes are identified as well as refined subsets of each relating to maturation and function. Expected function based on expression of specific markers within each subset is indicated.

  • cDC, conventional dendritic cells; CM, central memory; CTLA-4, cytotoxic T lymphocyte-associated protein-4; EM, effector memory; EMRA, terminally differentiated effector memory; gMDSCs, granulocytic myeloid-derived suppressor cells; ICOS, inducible T-cell costimulator; mMDSCs, monocytic MDSCs; NK, natural killer; PD-1, programmed cell death-1; pDC, plasmacytoid DC; PD-L1, programmed cell death ligand-1; Tim-3, T-cell immunoglobulin and mucin domain-3; Tregs, regulatory T cells.