Table 1 Phenotypes and functions of immunosuppressive cells within the TME

MDSCs [11, 12]

M-MDSCs

Mouse: CD11b⁺Ly6C^highLy6G⁻

Human: CD11b⁺CD14⁺CD33⁺HLA-DR⁻CD15⁻

CD11b⁺CD14⁺CD33⁺HLA-DR⁻CD15⁺

Induce Non-specific suppression; Produce cytokines that support tumor angiogenesis; Induce anti-tumor therapy resistance

PMN-MDSCs

Mouse: CD11b⁺Ly6G⁺Ly6C^low

Human: CD11b⁺CD14⁻CD15⁺CD33⁺HLA-DR⁻

CD11b⁺CD14⁻CD66b⁺

Induce antigen-specific T cell tolerance and non-specific suppression; Produce cytokines that support tumor angiogenesis

eMDSCs

Human: CD11b⁺CD14⁻CD15⁻CD33⁺HLA-DR⁻

Exist as free cells in the peripheral blood and as enriched cell populations in the tumor microenvironment

Macrophages [28]

M1

Mouse: CD11b⁺F4/80⁺CD206⁻

Human: CD64⁺CD80⁺

Produce immune killing molecules; Secrete specific inflammatory cytokines; Display pro-inflammatory features

M2

Mouse: CD11b⁺F4/80⁺CD206⁺

Human: CD163⁺CD86⁺

Remodel the ECM; Brake down the basement membrane; Promote angiogenesis; Construct immunosuppression; Recruit Tregs and MDSCs; Orchestrate tumor development and distant metastasis

Neutrophils [37, 38]

N1

Mouse: CD11b⁺Ly6G⁺CD54⁺CD16⁺CD170^low, CD177⁺ (in CRC)

Human: CD11b⁺CD66b⁺CD101⁺CD54⁺HLA-DR⁺CD86⁺CD15^highCD170^low, CD177⁺ (in CRC)

Associate with anti-tumor properties; Characterized by a normal density, a hypersegmented nucleus and a cytotoxic activity toward cancer cells

N2

Mouse: CD11b⁺Ly6G⁺PDL1⁺CD170^high

Human: CD11b⁺CD66b⁺PDL1⁺CD170^high

Associated with pro-tumor properties; Have immunosuppressive activity

N_I

Mouse: CD11b⁺Ly6G⁺CD117⁺CD170^lowCD101⁻CD84⁺JAML⁺

Human: CD11b⁺CD66b⁺CD117⁺CD10⁻CD16^int/lowLOX1⁺CD84⁺JAML⁺

Immature neutrophils endow with immunosuppressive properties appear in the circulation, primary tumors and metastases

N_ISG

Mouse: CD11b⁺Ly6G⁺, IFIT1, IRF7, RSAD2

Human: CD11b⁺CD66b⁺, IFIT1, IRF7, RSAD2

Neutrophils with interferon-stimulated gene signatures

Tumor-associated DCs [68, 69, 72]

Plasmacytoid DCs

Mouse: B220⁺CD11c^lowMHC-II⁺CD303⁺

Human: B220⁺CD11c^lowMHC-II⁺CD317⁺

Contribute to tumor-induced immunosuppression

Conventional DCs

Mouse: Lin⁻ZBTB46⁺MHC-II⁺CD141⁺;

Lin⁻ZBTB46⁺MHC-II⁺CD11c⁺; CD11b⁺

Induce Th2 responses; Suppress CD8⁺ T cell function

Inflammatory DCs

Mouse: CD11c⁺MHC-II⁺CD11b⁺F4/80⁺Ly6C⁺CD206⁺CD115⁺CD107b⁺FcɛRI⁺CD64⁺

Human: CD11c⁺CD115⁺CD1c⁺CD1a⁺FcɛRI⁺CD206⁺CD172a⁺CD14⁺CD11b⁺

Produce high levels of pro-inflammatory cytokines, such as TNF, IL-6, and IL-12

Tregs [52,53,54]

nTregs

CD4⁺CD25⁺Foxp3⁺CD127^lo/−

Maintain normal immune tolerance and control the inflammatory response

iTregs

CD4⁺CD25⁺Foxp3⁺CD127^lo/−

Inhibit the anti-tumor immune action of effector T cells, NK cells and DCs; Secrete inhibitory cytokines; Kill effector cells by granzymes and perforin; Produce factors to facilitate Tregs expansion and reinforce the suppressive environment

Bregs [72, 78, 79]

B10 cells

Mouse: CD5⁺CD1d^hi

Human: CD19⁺CD24^hiCD27⁺

Produce IL-10, and suppress effector CD4⁺ T cells, monocytes, and DCs; Induce Tregs through TGF-β

T2-MZP cells

Mouse: CD19⁺CD21^hi; CD23^hiCD24^hi

Human: CD19⁺CD24⁺CD38⁺

Produce IL-10, and suppress effector CD4⁺ T cells; Induce Tregs and decrease CD8⁺ T cells by TGF-β