Roles of the tumor microenvironment in the resistance to programmed cell death protein 1 inhibitors in patients with gastric cancer

Table 1 The relationship between immune cells in the tumor microenvironment and the resistance to programmed cell death protein 1 inhibitors in patients with gastric cancer

Types	Functions	Mechanism of PD-1 inhibitor resistance	The potential to reduce PD-1 inhibitor resistance in patients with GC
Cytotoxic T cells	Inhibit and eliminate tumor cells	Decrease the quantity and functionality of CD8+ T cells[6]	New intervention methods to enhance the functionality of cytotoxic T cells
M2 macrophages	Inhibit immune responses, accelerate the growth and proliferation of tumor cells	Release a variety of cytokines that can stimulate tumor cell proliferation, reduce the activity of immune cells[11]	Blocking the Th2-cell cytokines, reducing monocytes to differentiate into M2-type macrophages
Treg cells	Play a significant regulatory role in the low-immunity TME	Suppress the effector T cells’ activity and modulate the response of antitumor T cells[13]	Eliminating Treg cells in GC tissue during PD-1 inhibitor therapy
MDSCs	Participate in chronic inflammation, cancer, and autoimmune diseases	Induce T cell exhaustion and lead T cell to lose immune function and proliferation ability[19]	Blocking CXCR2 could reduce the frequency of PMN-MDSCs and enhance the effectiveness of anti-PD-1
TANs	Promote tumor cell proliferation and exhibiting a tumorigenic effect	Promote tumor progression through the GM-CSF-PD-L1 pathway[27]	Utilizing drugs or other treatment methods to inhibit the activity of these pathological neutrophils or suppress the GM-CSF/PD-L1 immune pathway
Others

PD-1: Programmed cell death protein 1; GC: Gastric cancer; MDSCs: Myeloid-derived suppressor cells; Treg cells: Regulatory T cells; TANs: Tumor-associated neutrophils; TME: Tumor microenvironment; Th2-cell: T helper 2 cell; CXCR2: CXC chemokine receptor 2; PMN-MDSCs: Polymorphonuclear myeloid-derived suppressor cells; GM-CSF: Granulocyte-macrophage colony-stimulating factor; PD-L1: Programmed cell death ligand 1.