Table 1 The characteristics of heterogeneous TAMC

TAM

Monocytic precursors in bone marrow, spleen and embryo

M1:

F4/80⁺CD11b⁺CD86⁺

M2:

F4/80⁺CD11b⁺CD206⁺

Embryo-specific:

CX3CR1^highCD11a^low

CD49d^low

(a) Differentiation: CSF-1, TGF-β, VEGF, platelet-derived growth factor

(b) Polarization: M1 (IFN-γ, lipopolysaccharide); M2 (IL-4, IL-13)

(c) Proliferation: GM-CSF and adenosine

Embryo-specific:

(a) AngII-AGTR1A increase HSCs retention

(b) EMPs buds from the yolk sac endothelium

(c) Colonize the embryonic tissue or liver

(d) Differentiate from the early or later wave

M1:

iNOS, ROS, IL-1β, TNF-α, IL-12, IFN-γ

M2:

ARG1, IL-10, TGF-β, VEGF, MMP

M1: (a) Kill tumor cells

(b) Activate NK cells and cytotoxic T cells

M2: (a) Inhibit T cells and NK cells activition

(b) Induce angiogenesis

(c) Promote tumor growth and invasion

(d) Recruit Tregs into TME

Embryo-specific: Pro-fibrotic

MDSC

M-MDSC: Monocytic precursors in bone marrow and spleen

PMN-MDSC: Granulocytic precursors, monocytic-like precursors in Bone marrow and spleen

M-MDSC:

CD11b⁺CD14⁺HLA-DR^–/loCD15⁻ (human), CD11b⁺Ly6G⁻Ly6C^hi (mouse)

PMN-MDSC: CD11b⁺CD14⁻CD15⁺/CD66b⁺ (human), CD11b⁺Ly6G⁺Ly6C^lo (mouse)

Splenic MDSC: PMN-like cell

(a) Differentiation: IL-1β, IL-6, S100A8-9, IFN-γ, IL-4, IL-13, IL-10

(b) Accumulation and expansion: IL-6, IL-10, TGF-β

Splenic MDSC-specific:

(a) Recruit specific HSPCs via CCL2/CCR2

(b) Endogenous GM-CSF signals and local education by the splenic stroma

M-MDSC:

iNOS, ARG1, IL-10, TGF-β

PMN-MDSC:

ROS, PGE2, IDO, ARG1

(a) Reduce the anti-tumor activity of T cells

(b) Inhibit NK cells, macrophages, dendritic cells function

(c) Induce Tregs

TAN

Granulocytic precursors in Bone marrow

CD15⁺CD16⁺CD66b⁺CD14⁻ (human), CD11b⁺Ly6G⁺ (mouse)

Polarization:

N1 (type 1 interferon);

N2 (TGF-β)

CCL2, CCL17

N1: Kill tumor cells directly

Activate dendritic cells, CD4⁺ T cells, etc

N2: Inhibit tumor cell apoptosis

Promote angiogenesis

Inhibit CD8⁺ T cells function

Promote tumor invasion and metastasis

Recruite macrophages and Tregs into TME

TADC

Dendritic cell precursors in bone marrow

pDC: BDCA-2⁺BDCA-4⁺IL-3Ra⁺

CD11c⁻ (human),

CD45R⁺CD317⁺Siglec-H⁺

CD11c^low (mouse)

cDC1: BDCA3⁺CD141^high

cDC2: BDCA1⁺CD1c⁺

moDC: Indistinguishable from cDC2

Development and maintenance of phenotype:

(a) pDCs: E protein transcription factor E2-2

(b) cDCs: E protein antagonist Id2

pDC: IDO, ICOSL, PD-L1, granulosase B

cDC1: TNF-α, IL-6, IL-8, IL-12, CXCL9, CXCL10

cDC2: IL-1β, IL-6, IL-12, IL-23

moDC: NOS2, CD40 L, TNF

pDC: Inhibit CD8⁺ T cells function

Induce Tregs

cDC1: Cross-presentation

Polarize and activate CD4⁺ T cells

Activate NK cell

Recruit CD8⁺ T cells into TME

cDC2: Activate CD4⁺ T cells

moDC: Promote CD8⁺ T cell to kill tumor cells

EDMC

CD45⁺ EPCs in extramedullary organ (especially spleen)

CD235a⁺CD71⁺CD11b⁺CD33⁺HLA-DR⁻ (human), Ter119⁺CD71⁺CD11b⁺Gr1⁺ (mouse)

(a) Tumors block the default erythrocyte differentiation pathway of CD45⁺ EPCs

(b) GM-CSF… mediate erythrocyte-myeloid trans-differentiation

High level of PD-L1, Arg-1, iNos, ROS, et al

Strong ability to inhibit CD8⁺T cell proliferation and IFN-γ production, promote tumor growth and invasion

B-MF

Pre-B in local tumor

CD19⁺CD79a⁺IgM⁺ TAM

(a) Tumors mobilize BM pre-B accumulation in the spleen

(b) Acquisition of myeloid characteristics: Tumors decrease PAX5 levels using M-CSF

High level of PD-L2, B7-H3, Marco, TGF-β, et al

(a) Inhibit CD4⁺ T cell and induce Treg

(b) Unique metabolic and inflammatory functions

(c) Strong phagocytic ability