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/inhibition	PD-L1+ CD8 – activation/inhibition	PD-L1+ B cells – activation/inhibition
PD-1+ CD4 – activation/inhibition	PD-1+ CD8 – activation/inhibition	PD-1+ B cells- activation/inhibition
CTLA-4+ CD4 – inhibition	CTLA-4+ CD8 – inhibition	5. Total NK
Tim-3+ CD4 – inhibition	Tim-3+ CD8 – inhibition	PD-L1+ NK – inhibition
41bb+ CD4 – costimulation	41bb+ CD8 – costimulation	PD-1+ NK – activation/inhibition
Ki67+ CD4 – proliferation	Ki67+ CD8 – proliferation	Tim-3+ NK – activation/inhibition
CD73+ CD4 – exhausted/suppressive	CD73+ CD8 – exhausted/suppressive	Ki67+ NK – proliferation
ICOS+ CD4 – activation	Naïve (CCR7+CD45RA+) CD8	NKp30+ NK – activation
ICOS+ PD-L1+ CD4 – activation/inhibition	Central memory (CCR7+CD45RA-) CD8	NKp46+ NK – activation
ICOS+ PD-1+ CD4 – activation/inhibition	PD-L1+ CM CD8 – activation/inhibition	NKG2D+ NK – activation
Naïve (CCR7+CD45RA+) CD4	PD-1+ CM CD8 – activation/inhibition	CD226+ NK – adhesion/activation
Central memory (CCR7+ CD45RA-) CD4	CTLA-4+ CM CD8 – inhibition	Mature (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 – costimulation	Effector 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 – inhibition	Functional 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 – costimulation	EMRA (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 – costimulation	Immature (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 – proliferation	PD-L1+ Tregs – activation/inhibition	Ki67+ immature NK – proliferation
CD73+ EMRA CD4 – exhausted/suppressive	PD-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 – inhibition	PD-L1+ MDSC – inhibition	PD-L1+ monocytes – inhibition
PD-1+ NK-T – activation/inhibition	PD-1+ MDSC – activation/inhibition	PD-1+ monocytes – activation/inhibition
Tim-3+ NK-T – inhibition	CD16+ MDSC – immature/suppression	Classical monocytes – phagocytic
Ki67+ NK-T – proliferation	Monocytic (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/inhibition	Intermediate monocytes phagocytic/proinflammatory
PD-1+ cDC – activation/inhibition	CD16+ mMDSC – immature/suppression	PD-L1+ intermediate monocytes – inhibition
Tim-3+ cDC – inhibition	Granulocytic (CD14- CD15+) MDSC	PD-1+ intermediate monocytes- activation/inhibition
Ki67+ cDC – proliferation	PD-L1+ gMDSC – inhibition	Non-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.