Table 1.
Therapeutic strategies targeting tumor immune tolerance in GC microenvironment.
| Drugs | Name | Target | Mechanisam | Reference |
|---|---|---|---|---|
| CAR-cell | MSLN-CAR-T | GC | Specifically kill MSLN-positive cells and release cytokines | (130) |
| CAR-cell | cMet-PD1/CD28 CAR-T | GC | Increase the infiltration of central memory T cells | (131) |
| CAR-cell | ICAM-1-CAR-T | GC | Specifically kill ICAM-1-positive cells | (132) |
| CAR-cell | CD133-CAR-T | GC | Target cisplatin-resistant gastric cancer stem cells | (133) |
| CAR-cell | CDH17-CAR-T | GC | Kill tumor cells in a CDH17-dependent manner and do not attack normal epithelial cells | (134) |
| CAR-cell | CLDN18.2-CAR-T | GC | Specifically kill CLDN18.2-positive cells, Phase I clinical trial | (135, 136) |
| CAR-cell | Trop2/PD-L1-CAR-T | GC | Specifically kill Trop2 and PD-L1positive cells | (137) |
| CAR-cell | NK expanded in vitro | GC | Combine with trastuzumab or cetuximab had a certain therapeutic effect on gastric cancer | (138) |
| CAR-cell | PD1-NKG2D-CAR-NK | GC | Enhance whole blood IFN-γ production and reduced peripheral Tregs, Phase I clinical trial | (139) |
| CAR-cell | MSLN-CAR-NK | GC | Specifically kill MSLN-positive cells and enhance NK cell infiltration | (140) |
| Monomer drug | Tranilast | Fibroblasts | Increase the infiltration of CD8+ T cells, and reduce the infiltration of M2 macrophages and mast cells, and reduce proliferation of fibroblasts | (141) |
| Monomer drug | Futibatinib | Fibroblasts | FGFR1-4 inhibitor, Antitumor effect | (142) |
| Monomer drug | Metformin | Fibroblasts | Promote the secretion of Calml3, Antitumor effect | (143) |
| Monomer drug | PPI | Fibroblasts | Inhibit the exosome secretion function of fibroblasts | (144) |
| Monomer drug | Itraconazole | Fibroblasts | Alleviate the resistance of gastric cancer cells to bevacizumab | (145) |
| Monomer drug | IPI549 | Macrophages | PI3K-γ inhibitor, restores macrophage function and promotes antitumor T cell responses | (86) |
| Monomer drug | MENK | Macrophages | Promote the M1 polarization, blocking the PI3K/AKT/mTOR signaling pathway | (146) |
| Monomer drug | Pam3Csk4 | T cell | TLR2 agonist, active CD8+ T cells | (18) |
| Monomer drug | DAC | T cell | Block DNA methylation in activated PD1+CD8+ TILs | (147) |
| Monomer drug | CCL28 inhibitor | T cell | Inhibit Treg cell infiltration | (148) |
| Herbal medical | Berberine | Macrophages | enhance the phagocytosis of macrophages and therapeutic effects of CD47 antibody and rituximab | (149) |
| Herbal medical | Paeoniflorin | Fibroblasts | Inhibit the secretion of IL-6, Antitumor effect | (149) |
| Herbal medical | Astragaloside IV | Fibroblasts | Inhibit the pathological functions of CAFs | (150) |
| Herbal medical | Triptonide | Fibroblasts | Abolish the ability of GCAFs to induce epithelial-mesenchymal transition | (151) |
| Herbal medical | Sophoridine | Macrophages | Inhibit M2 polarization,increase CD8+ T proliferation and cytotoxic function | (152) |
| Herbal medical | Oleanolic acid | T cell | Promote the balance of Treg/Th17 cells | (153, 154) |
| Biological agents | Oncolytic virus carrying relaxin relaxin | ECM | Degrade ECM components, increase accumulation of cytotoxic T cells and trastuzumab and PD-1 mAbs | (155) |
| Biological agents | Fiber-modified hexon chimeric recombinant oncolytic adenovirus | Fibroblasts | Kill gastric CAFs | (156) |
| Biological agents | Oncolytic herpes simplex virus type 1 virus G47Δ | Macrophages, NK | Decrease M2 macrophages,increase M1 macrophages and NK | (157) |
| Biological agents | PR-Gel | Macrophages, T cell | Increase CD8+ T-cell and M1 infiltration | (158) |
| Biological agents | CD137 antibody | T cell | Enhance CD8+ T cell | (159) |
| Biological agents | iRGD-anti-CD3 | T cell | Promote T cell infiltration | (160, 161) |
| Biological agents | sPH20-IgG2 | T cell | Enhance the cytotoxicity of MSLN CAR-T | (162, 163) |
| Biological agents | m3s193 BsAb | T cell | Enhance activity in T cell recruiting, activation, proliferation, cytokine release, and cytotoxicity | (164) |
| Biological agents | Hydroxypropyl cellulose photocrosslinked hydrogel incorporating IFN-α2b | T cell | Induce activated T cells into tumor tissue | (165) |
| Biological agents | αPD1-PEG-PCL | T cell | Target PD1+CD8+ TIL | (166) |
| Biological agents | DC cell vaccine loaded with MG-7 antigen | Dendritic cell | Activate specific cytotoxic T lymphocytes | (167) |
| Biological agents | Polylactic-co-glycolic acid nanoparticles encapsulated DC cells and gastric cancer cell soluble lysate | Dendritic cell | Enhance the differentiation of T cells to Th1, enhance the effect of DC vaccine | (168) |
| Biological agents | Dendritic cells modified by SLC | Dendritic cell | Promote DC maturation, enhance the ability of DCs to T cell chemotaxis and T cell stimulation | (169) |
| Biological agents | Heat shock protein -glycoprotein gp96 | Dendritic cell, NK | Enhance the antigen-presenting ability of DC | (170) |
| Biological agents | Fusion protein dsNKG2D-IL-15 | NK | Recruit and activate NK | (171) |
| Biological agents | Gastrin Vaccine | Gastrin | Increase CD8+ T lymphocytes and reduce the number of M2 macrophages | (72) |