Table 2.

Overview of drug treatment response via scRNA-seq in GC

Treatment regimens	Sample types	Key findings	References
Chemotherapy	GC patient tissues	After NACT, TME became an immunosuppressive environment with increased percentages of the endothelial cells and fibroblasts	[107]
	GC patient tissues	Responders showed chemotherapy-induced NK cell infiltration, macrophage repolarization, and increased antigen presentation. Increased LAG3 and decreased DC abundance were observed in non-responders	[108]
	GEO database	IGF1+ CAFs may induce drug-resistant phenotype through IGF1-α6β4 integrin ligand-receptor binding and activation of EMT biological process	[109]
	GEO database	Depleted ECM components and increased immune processes are two vital TME features associated with 5-FU beneficial responses in GC patients	[110]
	Gastric organoids from mice and GC patients	Pyrvinium specifically targeted CD133+/CD166+ stem cell populations and proliferating cells in dysplastic organoids	[111]
Immunotherapy	Mice	Combining PDGFRα/β blockade and anti–PD-1 treatment synergistically suppressed the growth of fibrotic tumors	[97]
	GC patient tissues	MSI-H GC patients had a genomic, immunologic, and response heterogeneity treated with pembrolizumab	[112]
	GEO database (GSE183904)	C5aR1 is a myeloid checkpoint, and C5aR1 blockade combining with PD-1 inhibitor displayed a synergistic effect	[93]
	GEO database (Kumar et al., and Jeong et al.)	Siglec-10 is a myeloid checkpoint, blocking it reinvigorates the antitumor immune response and synergistically enhances anti-PD-1 immunotherapy response in GC	[94]
	Ex vivo tumor slice cultures from fresh surgical resections of GC	GITR agonist generated a limited transcriptional response, while TIGIT antagonist orchestrated a multicellular response involving CD8+ T cells, Tfh-like cells, DCs, and Tregs	[80]
	GC patient tissues	APBhigh tumor exhibited immunotherapy resistance to immune checkpoint inhibitor	[68]
Immunochemotherapy	GC patient tissues	A high baseline IFN-γ signature in CD8+ T cells can better predict the response to the neoadjuvant immunotherapy plus chemotherapy	[113]
	GC patient tissues	ISG15+ CD8+ T cells, enriched in the EBV+ GC patients, indicated benefit from immunochemotherapy for GC patients	[114]
Targeted therapy plus immunotherapy	Humanized PDX models	CXCL5/CXCR2 blockade via apatinib can enhance anti-PD-1 immunotherapy for GC	[115]

scRNA-seq single-cell RNA sequencing, GC gastric cancer, NACT neoadjuvant chemotherapy, TME tumor microenvironment, NK natural killer cell, LAG3 lymphocyte activation gene 3, DC dendritic cell, GEO gene expression omnibus, CAF cancer-associated fibroblast, IGF1 insulin-like growth factor 1, EMT epithelial–mesenchymal transition, ECM extracellular matrix, 5-FU fluorouracil, PDGFR platelet-derived growth factor receptor, PD-1 programmed cell death protein 1, MSI-H microsatellite instability-high, GITR glucocorticoid-induced tumor necrosis factor receptor, TIGIT T cell Ig and ITIM domain, Tfh follicular helper T cell, Treg regulatory T cell, APB, alternate promoter burden, IFN-γ interferon gamma, ISG15 interferon-stimulated gene 15, EBV Epstein-Barr virus, PDX patient-derived xenograft, CXCL5 C-X-C motif chemokine ligand 5, CXCR2 C-X-C motif chemokine receptor 2