TABLE 2.
Therapeutic strategy targeting tumour‐associated macrophages (TAMs) in gastric cancer (GC).
| Strategy | Mechanisms | In vitro/in vivo model | Outcome | References |
|---|---|---|---|---|
| Repolarising TAMs (from M2 to M1) | αVEGFR2–MICA fusion antibodies | In vitro RAW 264.6, PBMCs, NK‐92 and in vivo BGC‐823 and AGS cell line | Induced the polarisation of RAW264.7 to M1 type and enhanced cellular cytotoxicity and anti‐tumour efficacy | 15 |
| Targeting TAMs in HER2‐positive GC | CD40×HER2 bispecific antibody, which targeted the CD40 to restore the ubiquitination level of TRAF6/3 and activate NF‐κB signalling, increased the M1 TAMs | In vitro RAW 264.6 and THP‐1 cell line and in vivo NCI‐N87 cell line | CD40×HER2 bispecific antibody increased M1 TAMs, enhanced anti‐tumour activity and overcome trastuzumab resistance in HER2‐positive GC | 16 |
| Enhancing the polarisation of M1 TAMs | PPARγ‐agonists (rosi) activated the NF‐κB pathway by elevating the expression of DOK1 | In vitro THP‐1 and AGS cell line | Elevated M1 TAMs populations and enhanced cytotoxic efficacy of macrophages towards AGS cells | 33 |
| Repolarising TAMs (from M2 to M1) | PI3K‐γ inhibitor (IPI‐549) | In vitro BMDMs and in vivo MFC cell line | IPI‐549 reversed the inhibition of phagocytosis, polarisation of M2 TAMs and enhanced anti‐tumour activity | 44 |
| Repolarising TAMs (from M2 to M1) | USP14 inhibitor (IU1) blocked the SIRT1/PGC1‐α axis | In vivo MFC cell line | IU1 repolarised TAMs from M2 to M1 and enhanced anti‐tumour activity | 45 |
| Repolarising TAMs (from M2 to M1) | Dextran sulphate blocked the IL‐6–STAT3 pathway induced by IL‐4 and IL‐13 | In vivo BGC‐823 | Dextran sulphate reduced the infiltration of M2 TAMs in intraperitoneal metastatic tumours | 60 |
| Repolarising TAMs (from M2 to M1) | Sophoridine activated the TLR4/IRF3 axis | In vitro RAW 264.6 and THP‐1 cell line and murine CD8+ T cells | Sophoridine repolarised TAMs from M2 to M1 and stimulated the proliferation and cytotoxic function of CD8+ T cells, and relieved CD8+ T‐cell exhaustion | 73 |
| Repolarising TAMs (from M2 to M1) | DKK1 antibody inactivated PI3K–AKT signalling by targeting DKK1 | In vitro BMDMs, CD8+ T cells and MFC cell line and in vivo MFC cell line | DKK1 antibody repolarised TAMs from M2 to M1 and boosted the tumour‐killing function of CD8+ T cells and the efficacy of PD‐1 inhibitors | 81 |
| Targeting SIGLEC10‐positive TAMs | SIGLEC10 antibody | In vitro tumour single‐cell suspensions | SIGLEC10 antibody enhanced the tumour‐killing function of CD8+ T cells | 131 |
| Repolarising TAMs (from M2 to M1) | Umbelliprenin decreased IL‐10 and increased IL‐12 and NO | In vitro THP‐1 cell line | Umbelliprenin significantly increased the M1/M2 ratio | 139 |
| Repolarising TAMs (from M2 to M1) | – | In vitro THP‐1 cell line | Jianpi Yangzheng Xiaozheng Decoction repolarised TAMs from M2 to M1 | 140 |
| Repolarising TAMs (from M2 to M1) | HSA‐Au (III) α‐N‐heterocyclic thiosemicarbazone compounds (5b) nanoparticles promoted the NF‐κB and iNOS and inhibited Msr2 and STAT3 | In vitro RAW264.7 cell line and in vivo MFC cell line | HSA‐5b nanoparticles promoted the polarisation of M1 TAMs and enhanced anti‐tumour activity and recruitment of CD4+ T cells, CD8+ T cells and NK cells in the tumours | 154 |
| Enhancing the polarisation of M1 TAMs | The immunonutrition activated the inflammatory pathway in TME | – | The immunonutrition increased the M1 TAMs infiltration and decreased the M2 TAMs infiltration in TME | 155 |
| Targeting M2 TAMs | A mannose‐conjugated chlorin (M‐chlorin) was designed to bind to the mannose receptor, which is highly expressed on M2 TAMs | In vitro THP‐1 cell line | Photodynamic therapy with M‐chlorin effectively induced M2 TAMs death | 156 |
| Targeting CD47‐positive TAMs | CD47 antibody | In vitro THP‐1 cell line and in vivo MFC cell line | CD47 antibody enhanced phagocytosis and IFN‐β secretions of TAMs in Epstein–Barr virus‐associated GC | 157 |
| Targeting C5aR1‐positive TAMs | C5aR1 antibody | In vitro tumour single‐cell suspensions | C5aR1 antibody promoted the secretion of pro‐inflammatory cytokines TNF‐α and IL‐1β by Dectin‐1+ TAM and boosted the tumour‐killing function of CD8+ T cells and the efficacy of PD‐1 inhibitors | 158 |
| Targeting Dectin‐1‐positive TAMs | Dectin‐1 antibody | In vitro tumour single‐cell suspensions | Dectin‐1 antibody promoted the secretion of pro‐inflammatory cytokines TNF‐α and IL‐1β by Dectin‐1+ TAM and boosted the tumour‐killing function of CD8+ T cells and the efficacy of PD‐1 inhibitors | 159 |
Abbreviations: BMDMs, bone marrow‐derived macrophages; HSA, human serum albumin; IL, interleukin; NF‐κB, nuclear factor‐kappa B; PBMCs, peripheral blood mononuclear cells; TME, tumour microenvironment; TNF‐α, tumour necrosis factor‐α.