Table 4.
Distinct subsets of immune cells in human/mouse tumor tissues.
| Myeloid lineage | ||||||
|---|---|---|---|---|---|---|
| Cell type | Subtypes | Expression markers | Significance/Functions | References | ||
| Human | Mouse | |||||
| Monocytes | Classical | CD14++, CD16−, FCN1 | Ly6C+ CCR2+CX3CR1int | Phagocytosis, innate sensing/immune responses and migration | (56, 79, 83, 84) | |
| Non-classical | CD14+, CD16++, CDKN1C, LILRB2, ITGAL | Ly6Clow CCR2−CX3CR1++ | Present antigen processing capabilities, promote neutrophil adhesion at the endothelial interface via the secretion of TNF-α | |||
| Intermediate | CD14++, CD16+, S100A8, S100A9,CSF3R, CCR5 | S100A8, S100A9, CSF3R, CCR5 | Express antigen presentation-related molecules, secrete TNF-α, IL-1β, IL-6, and CCL3 upon TLR stimulation | |||
| MonoDC | CLEC10A, MHC class II genes,CD74 | Not known | ||||
| TEMs | Tie2/TEK angiopoietin receptors | Tumor angiogenesis | ||||
| Classical (M1) | CD14+ S100A8/9+ | proinflammatory/antitumorigenic, polarize to M2 type in advance stage cancers | ||||
| Alternate/anti-inflammatory/protumorigenic (M2) | CD16+(FCGR3A), CD204, CD206,CD163 | promote immunosuppression, supportformation of abnormal vessels in TME that lead to tumor progression | ||||
| Myeloid-derived suppressor cells (MDSC) | HLA-DR-/low | Immunosuppressive activities, promote tumor cell survival, angiogenesis | ||||
| Dendritic cells | DC1 | CD141+, XCR1, CLEC9A, CADM1 | Antigen presenters to CD8+ T cells | (79, 82) | ||
| DC2 | CD1C+, CD1A,CD1C, CD1E, CD207, FCER1A | Interact with CD4+ T cells | ||||
| DC3 | CD1C-, CD141−, FSCN1, BATF3, IRF8, CCR7, LY75, CCL22, BIRC3, NFKB2, IL12B | Activated DC phenotype | ||||
| Plasmacytoid DCs (pDC) | TCF4, LILRA4, CLEC4C (CD303), IL3RA | Initiate inflammatory responses, produce IFN-γ, also known to promote immunosuppressive environment | ||||
| Neutrophils | Human | Mouse | Human | Mouse | (79, 126) | |
| N1 | N1 | S100A12 | MMP8 | antitumor activity, induce activation of T, B, NK and DC cells, ROS production | ||
| N2 | N2 | IFIT1 | IFIT1 | pro-tumor activity, secrete ECM remodeling enzymes and pro-angiogenic factors | ||
| N3 | N3 | CASS4 | CXCL3 | – | ||
| N4 | N4 | CTSC, HEXB, PTMA | PALD1, SIGLECF | Found in healthy lung tissues, function unknown | ||
| N5 | N5 | CCL3 | CCL3, SIGLECF | Found in healthy lung tissues, expressed cytokines CCL3 and CSF1, CSTB, CTSB, and IRAK2 | ||
| – | N6 | - | CTSC, SIGLECF | – | ||
| Mast cells | Mast 1 | DAGLB, LTC4S, ALPI, KIT and MS4A2 | Involved in pro-tumoral and antitumoral functions, release cytokines: IL-1, IL-4, IL-8, IL-6, MCP-3, MCP-4, TNF-α, IFN-γ, LTB4, TGF-β, IL-8, VEGF, FGF-2, NGF, heparin, tryptase | (79) | ||
| Mast 2 | CMA1, CTSG, ADCYAP1, MRO, HPGD, FUZ, MAPK6 | |||||
| Lymphoid lineage | ||||||
| T cell | Helper T cells | CD4+ | Anti-tumor response | (18, 19, 44, 89) | ||
| Cytotoxic T cells | CD3+, CD8+, PDCD1 | Antitumor cells, express IFNγ, Prf1(perforin), granzyme B | ||||
| Regulatory T cells | CD4+, FOXP3, IL2RA, CD25, CTLA-4, ENTPD1 (CD39) | Immunosuppressive cells | ||||
| Effector Memory T cells | CD4+, CD8+, CD197−, CD45RA− | Shows signs of dysfunction at later cancer stages, | ||||
| Exhaustive T cells | PD-1+, CD8+, TIM-3, CTLA-4, HLA-DR, CD38 | Characteristic of advanced-stage tumors, anti- PD1 therapy response | ||||
| γδT cells | TRDC+ and TRGC2+ | Cytotoxic lymphocyte, express IL17 | ||||
| B cell | Follicular B cells | CD20 (MS4A1), CXCR4, HLA-DR, | Gives rise to naïve/memory B cells | (44, 114) | ||
| Naïve B cells | CD27−, IGHD+(IgD)/IGHM+(IgM), | Gives rise to other B cell types | ||||
| Memory/Effector B cells | CD27+, Granzyme B, TRAIL, MHC I, MHC II,IFNγ, IL-12 | Direct tumor cell killing, antigen presentation, macrophage polarization to M1, CD4+ T cell conversion | ||||
| Plasma B cells | MZB1, SDC1/CD138, PRDM1, IgG1 | Antibody secreting cells, opsonization, complement system activation, ADCC, antibody-mediated phagocytosis, antigen presentation by dendritic cells, drive cytotoxic T cell responses | ||||
| Mucosa-associated IgA+ B cells | IgA+, CD20−/CD19+ | Immunosuppressive, convert CD4+ T cells to Treg, promote angiogenesis, macrophage polarization, MDSC development | ||||
| Germinal center B cells | CCR7, GPR183, IGHM | Undergoes class switch recombination to form other immunoglobin subtypes | ||||
| Regulatory B cells | PD-1, CD80, CD86 | Immunosuppressive, express inhibitory ligands and cytokines, inhibit T cell and NK cell response | ||||
| NK cell | CD56− | CD16, KIR, CD57, CD69, CCR7, perforin++ | Mediates natural and antibody-dependent cellular cytotoxicity, exhibiting high levels of perforin and enhanced killing | (89, 127) | ||
| CD56+ | highILT2, lowNKp46, NKG2D, NKp30, DNAM1, CD16 | Low levels of perforin, and are primarily specialized for cytokine production | ||||
| CD56+, perforinlow | CD56, NKG2A, CD27, KIR | |||||
| CD56+, CD16low | CD9, CXCR3 | |||||
| NK-T cells | KLRD1, FGFBP2, CX3CR1, CD8B+CD3D+ | Anti-tumorigenic in early tumor stages, show immunosuppressive activities in late-stage tumors | ||||