Metabolic regulation of tumor-associated macrophage heterogeneity: insights into the tumor microenvironment and immunotherapeutic opportunities

Qian, Yujing; Yin, Yujia; Zheng, Xiaocui; Liu, Zhaoyuan; Wang, Xipeng

doi:10.1186/s40364-023-00549-7

Table 1 Classification and characterization of TAM subtypes from M1/M2 to single-cell sequencing insights

From: Metabolic regulation of tumor-associated macrophage heterogeneity: insights into the tumor microenvironment and immunotherapeutic opportunities

TAM subtypes		Signature	Cancer types	Factors Secreted by TAMs	Functions	Ref.
Traditionally defined populations	M1	CD80, CD86, CD68, MHC-II, iNOS, TLR-4	LC	IL-12, IL-6, TNF-α	Pro-inflammatory, tumor resistance	[38]
	M2a	CD163, CD206	CC	IL-1R, IGF, TGF-β, CCL17, IL-10	Anti-inflammatory, tissue remodeling	[39, 40]
	M2b	CD86, TNF	LC	IL-10	Immunoregulation, tumor progression	[38, 40]
	M2c	CD163, CD206, TLR-1, CCR2	Melanoma	TGF-β, IL-10	Phagocytosis of apoptotic cells	[32, 40]
	M2d	CD86, iNOS	lymphoma	VEGF, IL-10	Angiogenesis, tumor progression	[32, 40]
Major populations defined by scRNA-seq insights	SPP1⁺	SPP1, PMAIP1, INHBA, KLF2/6, NEDD9, G0S2	CRC, OS, GC, OC	CCL2/3/4, CXCL1/2/3/5/8, IL-6	tumor angiogenesis, Recruiting immune cells	[11, 16, 36, 41, 42]
	FOLR2⁺	FLOR2, CD163, CD206, TIM4	HCC, BRCA, LUAD, OC	CCL17/19/22	CD8 + T-cell infiltration, Tregs interaction, immunosuppression	[11, 43,44,45]
	TIE2⁺	TIE2, VEGFR, CCR2, CXCR4	OC, BRCA	CCL2, VEGF, MMP7	Metastasis, angiogenesis tumor progression	[46,47,48]
	TREM2⁺	TREM2, ZEB1, FABP5, CD163, CD36, CD63, AOPE, APOC1	CRC, OS, GC, NSCLC, BRCA	CCL18, LPL, MMP7/9/12, SPARC	Lipid metabolism, immunosuppression, matrix remodeling	[37, 41, 42, 49, 50]
	MARCO⁺	MARCO, Arginase, MHC-II, MRC1	CRC, BRCA, GC, HCC	Arginase, IL-10, CCL22	Immunoregulation, tumor progression	[49, 51]
	FCN1⁺	FCN1, FLT1, FN1, CEBPB, CD163, CD52, CXCR4, TIMP1, VCAN	CRC, GBM, BRCA, HCC, OC	CCL2/4/20, IL1B, IL1RN, IL8, MIF, VEGFA	Angiogenesis, tumor progression	[11, 41, 43, 45, 52]
	C1QC⁺	C1QC, C1QB, C1QA, APOE, TREM2, GPNMB, SLCO2B1, APOC1, RNASE1, AXL	BRCA, OS, UCEC, CRC	C1QC, C1QB, C1QA, APOE, APOC1, CCL2/8, CXCL8/10	Phagocytosis, tumor progression	[41, 50, 51, 53]
	ISG15⁺	ISG15, IFITM3, GBP1, IL1RN	CRC, BRCA, GC	CCL2, CXCL10	Pro-inflammatory	[49,50,51]

TAMs display both M1 and M2 markers, challenging the adequacy of the M1/M2 dichotomy. scRNA-seq uncovers a richer diversity of TAM subtypes with varied phenotypes and functions cohabiting the tumor landscape. LC Lung Cancer, CC Cervical Cancer, SPP1 Secreted Phosphoprotein 1, CRC Colorectal Cancer, OS Osteosarcoma, GC Gastric Cancer, OC Ovarian Cancer, FLOR2 Folate Receptor 2, HCC Hepatocellular Carcinoma, BRCA Breast Cancer, LUAD Lung Adenocarcinoma, TIE2 Tyrosine Kinase with Immunoglobulin-Like and EGF-Like Domains 2, TREM2 Triggering Receptor Expressed On Myeloid Cells 2, UCEC Uterine Corpus Endometrial Carcinoma, MARCO Macrophage Receptor With Collagenous Structure, FCN1 Ficolin 1, GBM Glioblastoma Multiforme, PDAC Pancreatic Ductal Adenocarcinoma

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ISSN: 2050-7771

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