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Table 1 Human TAM subtypes and markers identified by scRNA-seq

From: Macrophage-derived exosomes in cancer: a double-edged sword with therapeutic potential

Cancer type

TAM subtype

Characteristic markers

Findings

References

scRNA-seq data

Breast cancer

Mac: CXCL10

CXCL10, PD-L1, PD-L2

Resemble “M1-like” phenotype

[77]

GSE176078

 

Mac: EGR1

EGR1

Resemble “M2-like” phenotype

  
 

Mac: SIGLEC1

SIGLEC1

Resemble “M2-like” phenotype

  
 

LAM1: FABP5

FABP5, TERM2, CCL18, PD-L1, PD-L2

Obesity and lipid metabolism

Immune regulation and tumor promotion

  
 

LAM2: APOE

APOE, TERM2, CCL18, PD-L1, PD-L2

Obesity and lipid metabolism

Immune regulation and tumor promotion

  
 

Cluster0 (TERM2)

APOE, TREM2, CADM1, SPP1, ISG15, LYZ, FCN1

Cancer development

[78]

GSE192935,GSE114725

 

Cluster1 (TREM2)

APOE, TREM2, SPP1, ISG15, APOC1, CTSD

Cancer development

  
 

Cluster2 (FOLR2)

APOE, FOLR2, SEPP1, SLC40A1, MRC1, LYVE1

Tissue-resident macrophages

Immune promotion

Positively correlate with better prognosis

  
 

MAC-CXCL2

C5AR1

Not reported

[79]

GSE206638

 

MAC-FBP1

MT1X-G-H, FN1

Not reported

  
 

MAC-FCGBP

FCGBP, CD1A, TACSTD2

Not reported

  
 

LAM-APOC1

APOC1, APOE, TREM2, GPNMB, FOLR2, LAG3, PDCD1LG2, CD200

Lipid metabolism, antigen cross-presentation, IFN-α and -γ signaling pathways

  
 

LAM-STAB1

STAB1, TREM2, GPNMB, APOE, LYVE-1, FOLR2, CD209, CD276, PDCD1

Lipid metabolism, tumor promotion, MMP and collagen degradation pathways

  

Colorectal cancer

C1QC+ MRC1 macrophage

C1QC+ MRC1

Not reported

[80]

HRA000979

 

SPP1+ macrophage

SPP1, FCGR3A, C1QC, MRC1, ITGAM, ANPEP,

Polarization of macrophages, shorter PFS, immunotherapy resistance

  
 

VCAN+ macrophage

VCAN, FCGR3A, MRC1, ANPEP

Not reported

  
 

THBS1+ macrophage

FCGR3A, C1QC1, MRC1, CD209, CMKLR1

Antigen presentation, the intestinal immune network regulation for IgA production

  
 

S100A9 Mac/Mono

S100A9high

Immunosuppression

[81]

GSE56699,GSE14333,GSE39582,GSE17536,GSE17537,GSE33113,GSE37892

 

Cluster0

STAB1, SIRPα

Immune escape

[82]

GSE178341

 

Cluster1

MACRO, SPP1, SIRPα

Immune escape

  
 

Cluster2

FTL

Not reported

  
 

Cluster3

MKI67, SIRPα

Immune escape

  
 

Cluster4

Not reported

Not reported

  
 

Cluster5

FOLR2

Not reported

  
 

OAS+ macrophage

OAS1

Innate immune response

[83]

HRA003569

 

OLR1+ macrophage

OLR1

G protein-coupled receptor and growth factor receptor binding

  
 

FOLR2+ macrophage

FOLR2

Tissue-resident macrophage, lipid metabolism, anti-inflammation

  

Gastric cancer

Pro-inflammatory macrophage

S100A8, S100A9, IL1B, CXCL8

Negatively correlated with anti-inflammatory macrophage

[84]

GSE206785

 

Anti-inflammatory macrophage

APOE, MAF, C1QB, SEPP1

Reduced survival

  
 

Tissue-resident macrophage

F13A, CCL2, FOLR2, CCL2, LYVE1, SEPP1, F13A1

Not reported

  
 

Mφ_THBS1

IL1B, NLRP3, VEGFA, EREG, MITF, NR1H, TFEC

Tissue-resident macrophages

[85]

HRA000704

 

Mφ_APOE

APOE, TREM2, C1QA, GPNMB, GRN, CD63, LAMP1

Lipid-associated and lysosome functions

Tumor progression

  

Glioblastoma

MARCO+ macrophage

MARCO

Tumor progression, poor clinical outcomes, mesenchymal trait, hypoxia

[86]

GSE141383

 

GPNMB+ macrophage

GPNMB

Promote PN-MES transition and impede T cell activation

[87]

GSE103224, GSE138794,GSE139448,GSE131928

 

MPO+ macrophage

MPO

Anti-tumor cytotoxic function

[88]

GSE154795, GSE162631

 

Proliferating TAM (C7)

MKI67

Not reported

[89]

HRA004677

 

IL1+ TAM (C6)

IL1

Inflammatory response pathways, macrophage activation

  
 

Undefined cluster (C5)

Not reported

Not reported

  
 

SIGLEC9+ SEPP1+ TAM (C2)

SIGLEC9, SEPP1

Immunosuppression, angiogenesis Monocyte-derived macrophage

  
 

SIGLEC9+ MARCO+ TAM (C9)

SIGLEC9, MARCO

Immunosuppression

Monocyte-derived macrophage

  

Hepatocellular carcinoma

TREM2+ TAM (C6)

TREM2

Anti-inflammation

[90]

GSE149614

 

MoMF (C16, C26)

FCN1hi, LYZhi, VCANhi,

CD68lo, CD14lo, FCGR3Alo

Monocyte-derived macrophage

  
 

VEGFA+ TAM (C21)

VEGFA, NFKB1, HSPA1A, HSPA1B

Oxidative stress

  
 

MPP9+ TAM (C23)

CD45+, CD68+, CD11b+, MMP9+, SPP1, ITGAM

Tumor progression, migration, invasion, and angiogenesis, associated with worse overall survival

  
 

SPP1+ macrophage

SPP1, TREM2

Hypoxia, tumor progression, phagocytosis suppression

[91]

Mendeley Data (skrx2fz79n)

 

FOLR2+ macrophage

FOLR2, APOE, C2

Not reported

  
 

CXCL10+ macrophage

APOBEC3A

Polarization of proinflammatory macrophages

Monocyte-derived macrophage

  
 

CCL3L1+ macrophage

CD74, HLA-DR, HLA-DP, HLA-DQ

Antigen presentation

Monocyte-derived macrophage

  
 

Proliferating macrophage

Not reported

Not reported

  
 

CXCL10+ TAM

CXCL9, CXCL10, STAT1, IDO1, GBP1

T cell recruitment, IFN -γ signalling, response to atezo/bev

[92]

EGAS00001007547

 

PPT1+ macrophage

Galectin-9hi, CD172ahi, CCR2hi, CD80lo, CCR7lo

High infiltration of T cells but immune exhaustion and immunosuppression, worse clinical outcome

[93]

GSE125449

 

TREM2 Macro

TREM2, APOE, APOC1

Microvascular invasion, similar to LAM, anti-inflammation

[94]

GSE242889

SCLC

IPF-associated pro-fibrotic macrophage

CD14, CD1, CD81, ITGAX, CSF1R, SPP1, CD74, VSIG4

ECM deposition and remodeling, immune inhibition

[95]

N/A

NSCLC

FABP4-MΦ

FABP4

Enriched in LUAD, phagocytosis, fatty acids and obesity,

[96]

SCIENCEDB.02028

 

FCN1-Mφ

FCN1, SPP1

Enriched in LUAD, phagocytosis

  
 

SPP1-Mφ

SPP1, SELENOP, FCN1

Enriched in LUSC, proinflammatory and anti-tumor function, tumorigenesis, angiogenesis

  
 

SELENOP-Mφ

SELENOP

Good prognosis, local antioxidant capabilities, lymphocyte activation, nucleoside phosphate metabolism

  

Pancreatic cancer

IL1B+ TAM

IL1B, IL1A, NLRP3, PTGS2, CCL3

Inflammatory response, leukocyte recruitment, angiogenesis

[97]

GSE217847

 

MKI67+ TAM

MKI67, TOP2A, PCLAF, UBE2C, TK1

Cell cycle

  
 

FOLR2+ TAM

FOLR2, LYVE1, SELENOP, SLC40A1, MRC1

Tissue-resident macrophages

  
 

SPP1+ TAM

SPP1, MARCO, FBP1, APOC1, LIPA

Lipid metabolism, phagocytic receptor expression

  
 

HSP+ TAM

HSPA6, SERPINH1, BAG3, HSPB1, HSPD1

Not reported

  
 

MT+ TAM

MT1H, MT1G, MT1X, MT1E, MT2A

Not reported

  

Pancreatic ductal adenocarcinoma

SPP1TAM

SPP1, MIF, CXCL8, TREM2

Tumor infiltrating CD8+ T cell exhaustion

[98]

GSE231535

 

GRNTAM

GRN, APOC1

Monocyte-derived macrophage, CD8+ T cell exclusion

  
  1. MMP matrix metalloproteinases, PFS progression-free survival, PN proneura, MES mesenchymal, atezo/bev atezolizumab/bevacizumab, LAM lipid-associated macrophage, IPF idiopathic pulmonary fibrosis, LUAD lung adenocarcinoma, LUSC lung squamous cell carcinoma, HSP hot-shock protein, MT Metallothionein