Table 2.
Targeting proteins in the crosstalk between TAMs and cancer cells.
| Ligand | Effector | Tumor | Inhibitor | Anti-Tumor Mechanism | Ref. |
|---|---|---|---|---|---|
| Inhibit the proliferation of cancer cells | |||||
| IL-10 | PD-L1 | NSCLC | BFD | Decrease IL-10 induced PD-L1 expression | [88] |
| IL-10 | STAT3 | RCC | N/A | Inhibit BMP-6 induced M2 polarization | [89] |
| MCAD | Lipid | BC | Sc-98926 | Reduce LD accumulation in TAMs | [67] |
| MIF | IL-2 | CRC | NIHIII.D.9 | Decrease Treg generation and IL-2 production | [90] |
| EGFR | ILT4 | NSCLC | Human ILT4 antibody | Inhibit TAM recruitment and M2 polarization | [91] |
| MK2 | IL-1, IL-6, TNF-α | CRC | PF364402 | Inhibit IL-1β, IL-6, and TNF-α, expression | [92] |
| Inhibit the invasion of tumor | |||||
| Lactate | Gpr132 | BC | N/A | Inhibit lactate uptake and M2 macrophages activity | [61] |
| IGFBP2 | FcγRIIB | GBM | Bs-1108R | Increase CD8+ T and p-CD19+ B cells and decreases M2 macrophages | [93] |
| S100A8/A9 | MMP2, MMP9 | LCC | N/A | Decrease MMP2 and MMP9 | [94] |
| GS | Glutamine | N/A | MSO | Suppress M2 macrophages, induce T-cell recruitment | [95] |
| ATM | ATR | BC | Clone 10H11.E12 | Decrease pCREB expression | [86] |
| Inhibit the angiogenesis of tumor | |||||
| IL-10/IL-13 | N/A | RCC | Let-7d | Inhibit intratumoral macrophage M2 polarization | [47] |
| S100A7 | JAB1 | ESCC | N/A | Inhibit S1007A induced phosphorylation of ERK and FAK | [96] |
| N/A | PI3K/Akt/mTOR | HCC | Apigenin | Inhibit PI3K/Akt/mTOR pathway | [97] |
| S1PR1 | NLRP3 | BC | N/A | Inhibit S1PR1 dependent IL-1β expression | [98] |
| LOX | β1 integrin/PYK2 | GBM | BAPN | Decrease TAM-derived SPP1 | [99] |
| Inhibit the stemness of tumor | |||||
| α-KG | Jmjd-3 | N/A | BPTES | Suppressed IL-4-induced STAT6 phosphorylation | [62] |
| LSECtin | BTN3A3 | BC | 5E08 | N/A | [100] |
| CCL8 | Erk1/2 | GBM | SCH772984 | Attenuate pseudopodia formation | [101] |
| IL-8 | STAT3 | OC | IL-8 Ab | Inhibit STAT3 and increase IL-12, NO | [102] |
| CBX8 | H3K4me3 | CRC | N/A | Increased the chemosensitivity of CRC cells | [103] |
RCC: renal cell carcinoma; CRA: cervical cancer; ESCC: esophageal squamous cell carcinoma; EGF: endothelial growth factor; IGFBP2: insulin-like growth factor binding protein 2; Gpr132: G-protein-coupled receptor 132; PPARγ: peroxisome proliferation-activated receptor-γ; α-KG: α-ketoglutarate; GS: glutamine synthase; TNF-α: tumor necrosis factor-α; TGF-β: transforming growth factor-β; CHA: chlorogenic acid; MMP: matrix metalloproteinase; ERK: extracellular regulated protein kinase; mTOR: mechanistic target of rapamycin; MIF: macrophage migration inhibitory factor; MK2: MAPK-activated protein kinase 2; S1PR1: sphingosine-1-phosphate receptor 1; LOX: lysyl oxidase; LSECtin: liver sinusoidal endothelial cell lectin; CBX8: chromobox protein homolog 8; H3K4me3: histone H3 lysine 4 trimethylation; jmjd-3: Jumanji domain-containing protein D3; Gpr132: G-protein coupled receptor G2A; FcγRIIB: Fc gamma receptor IIB; PYK2: proline-rich tyrosine kinase 2; NLRP3: NOD-, LRR- and pyrin domain-containing protein 3; MSO: methionine sulfoximine; BPTES: bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide; BAPN: beta-Aminopropionitrile monofumarate; BFD: bu fei decoction; MCAD: medium-chain acyl-CoA dehydrogenase; ATM: ataxia telangiectasia mutated; ATR attenuated total reflectance; N/A: not applicable.