Table 1.

Effect and mechanism of cancer cell-derived factors in regulating immune cell biology

Cancer cell-Derived factors	The mechanism for regulation in cancer cells	Targeting immune cells	Effect and mechanism in regulating immune cell biology	Ref
LOX	PTEN mutation/deletion activates YAP1 to upregulate LOX	Macrophage	Increasing macrophage migration via activation of the PYK2 signaling	[3]
CCL2	TP53 mutation activates NF-κB to upregulate CCL2 and TNFα	Macrophage and microglia	Increasing macrophage and microglia migration	[134]
TNFα
CCL5	Nf1 deficiency promotes CCL5 and CX3CL1 production	Macrophage and microglia	Increasing macrophage and microglia migration	[135]
CX3CL1
CHI3L1	CHI3L1 is regulated by the PI3K/AKT/mTOR pathway	Macrophage	Increasing macrophage migration and immunosuppressive polarization	[27]
CSF2	Unknown	Macrophage and microglia	Increasing macrophage and microglia migration; Decreasing macrophages and microglia apoptosis	[31]
SLIT2	Unknown	Macrophage and microglia	Increasing macrophage and microglia migration and immunosuppressive polarization via ROBO1/2-mediated PI3Kγ activation	[33]
P-selectin	Unknown	Microglia	Increasing microglia immunosuppressive polarization via the P-selectin-PSGL-1 axis	[34]
SPP1	Unknown	Macrophage	Increasing macrophage migration and immunosuppressive polarization	[32]
OLFML3	CLOCK-BMAL1 complex transcriptionally upregulate OLFML3	Microglia	Increasing microglia infiltration	[40]
LGMN	CLOCK-BMAL1 complex transcriptionally upregulate LGMN; OLFML3 upregulates LGMN via the HIF1α signaling	Microglia	Increasing microglia infiltration and immunosuppressive polarization via the CD162 signaling	[41]
CSF1	SETDB1 upregulates CSF1 via the AKT/mTOR signaling	Macrophage	Increasing macrophage migration	[42]
CXCL8	Neutrophil-derived NETs interact with the receptor for advanced glycation end-products on cancer cells to upregulate CXCL8 by activating the ERK/NF-κB signaling pathway	Neutrophil	Increasing neutrophil migration	[77]
	ALKBH5 demethylates stabilizes lncRNA NEAT1 to promote CXCL8 generation via the NEAT1/paraspeckle axis	Macrophage and microglia	Increasing macrophage migration	[45]
Extracellular lipid	Lipid loading augments hypoxia-mediated secretion of pro-tumorigenic factors (VEGF and HGF)	Macrophage	Increasing macrophage migration	[49]
PGE2	ARS2 directly activates MAGL to upregulate PGE2	Macrophage	Increasing macrophage immunosuppressive polarization	[51]
Kyn	Trp-catabolic enzymes activate Kyn pathway	Macrophage	Increasing macrophage migration by activating the AHR-CCR2 axis; Increasing macrophage immunosuppressive function by upregulating CD39	[54]
MIF	Unknown	MDSC	Increasing MDSC immunosuppressive function	[59]
CXCL1/2	Unknown	MDSC	Increasing MDSC migration by upregulating S100A9-ERK1/2 and p70S60k	[63]
miR-1246	Hypoxia increases miR-1246 expression and packaging by upregulating POU5F1 and hnRNPA1	MDSC	Promoting MDSC differentiation and activation by activating the DUSP3/ERK pathway	[64]
PD-L1	Wnt ligand and activated EGFR promote PD-L1 expression by inducing the binding of β-catenin/TCF/LEF to the CD274 promoter	T-cell	Inhibiting T-cell activation and infiltration	[94]
ICOSLG	ICOSLG expression is increased in mesenchymal GSCs in a TNFα/NF-κB dependent manner	Treg	Increasing Treg infiltration and IL-10 production	[97]

Abbreviations: AHR, aryl hydrocarbon receptor; AKT, protein kinase B; ALKBH5, alkB homologue 5; ARS2, arsenite-resistance protein 2; BMAL1, aryl hydrocarbon receptor nuclear translocator like; CCL2/5, C-C motif chemokine ligand 2/5; CCR2, C-C motif chemokine receptor 2; CHI3L1, chitinase-3-like 1; CLOCK, circadian locomoter output cycles protein kaput; CX3CL1, C-X3-C motif chemokine ligand 1; CSF1/2, macrophage-colony stimulating factor1/2; CXCL8, C-X-C motif chemokine ligand 8; DUSP3, dual specificity phosphatase 3; EGFR, epidermal growth factor receptor; Erk, extracellular signal-regulated kinase; GBM, glioblastoma; HGF, hepatocyte growth factor; HIF1α, hypoxia-inducible factor 1-alpha; HMGB1, high mobility group box protein 1; hnRNPA1, heterogeneous nuclear ribonucleoprotein A1; IL, interleukin; Kyn, kynurenine; LEF, lymphoid enhancerbinding factor; LGMN, legumain; LOX, lysyl oxidase; MAGL, monoacylglycerol lipase; MDSC, myeloid-derived suppressor cells; mTOR, mammalian target of rapamycin; NEAT1, nuclear enriched abundant transcript 1; NF1, neurofibromin 1; NF-κB, nuclear factor kappa B; OLFML3, olfactomedin-like 3; PD-L1, programmed death-ligand 1; PGE₂, prostaglandin E₂; PI3K, phosphoinositide 3-kinase; POU5F1, POU class 5 homeobox 1; PTEN, phosphatase and tensin homolog; PYK2, protein tyrosine kinase 2 beta; RAGE, receptor for advanced glycation endproducts; SETDB1, SET domain bifurcated histone lysine methyltransferase 1; SRC, proto-oncogene tyrosine-protein kinase Src; TCF, T cell-specific factor; TNFα, tumor necrosis factor alpha; Treg, regulatory T cell; Trp, tryptophan; VEGFA, vascular endothelial growth factor A; YAP1, yes-associated protein 1.