. 2021 Mar 9;11(10):2957–2972. doi: 10.1016/j.apsb.2021.03.004

Table 3.

Immune mechanism of TCMs as PD-1/PDL-1 inhibitors.

TCM	Immune mechanism
Saposhnikovia root extract Prim-O-glucosylcimifugin (POG)⁹³	Inhibited the proliferation, metabolism and immunosuppressive ability of PMN-MDSCs, improved the tumor immunosuppressive microenvironment Created a synergistic effect with PD-1 inhibitors
Total glucosides of paeony (TGP)⁹⁴	Increased the expression of PD-1/PD-L1 in the peripheral blood mononuclear cells Downregulated Treg cells/T helper 17 cells
Ganoderma lucidum⁹⁵	Mediated the immunomodulation effect of PD-1 increased the expression of CCL5 chemokine in the cultured B-lymphocytes
Astragalus polysaccharides (APS) extracted from astragalus membranaceus⁹⁶	Inhibited MOG_35-55-specific T cell proliferation and reduced the immune cytokines expression of IFN-γ, TNF-α, IL-2, IL-17, IL-4 and IL-10 Up-regulated the expression of PD-1 and PD-L1
Icaritin isolated from Epimedium⁹⁷	Effectively decrease tumor burden in a T-cell dependent manner and increased CD8 T-cell infiltration and increased effector memory T-cell frequency Reduced frequency of CD11b⁺ Gr1⁺ MDSCs infiltration and downregulation of PD-L1 expression and the expression of PD-L1 on neutrophils
Gegen Qinlian decoction⁹⁸	The combination of GQD and anti-mouse PD-1 could potently inhibit the growth of CT26 tumors in a xenograft model Enriched gut microbiota and altered metabolic signaling pathways Increased the proportion of CD8⁺ T cells in peripheral blood and tumor tissues, increased the expression of IFN-γ, downregulated PD-1 and increased IL-2 levels
Ginseng and Astragalus granules⁹⁹	Increased the level of insulin and reduced the level of blood glucose Increased both CD4⁺FoxP3⁺ and CD8⁺CD122⁺PD-1⁺ Treg numbers in both spleens and lymph nodes of NOD mice Reversed a decline in CD4⁺FoxP3⁺ Tregs The percentage of effector/memory CD8⁺ T cells (CD44^highCD62L^low) was significantly reduced and attenuated cellular infiltration and lowered CD3⁺ T cell numbers around and in islets
SORICM02 (Curcumae Rhizoma, Radix Paeoniae Rubra, Rhizoma Smilacis Glabrae, Mume Fructus, and Sarcandrae Herba)¹⁰⁰	Significantly inhibited murine skin allograft rejection and reduced graft-infiltration of CD3⁺ T cells increased CD8⁺CD122⁺PD-1⁺ Treg frequency with CD4⁺FoxP3⁺ Tregs remaining unchanged Hindered CD11c⁺ DC maturation post transplantation Induced CD8⁺CD122⁺PD-1⁺ Tregs Suppressed T cell proliferation in vitro and inhibited both mTOR and NF-κB signaling pathways increased IL-10 production, reduced IFN-γ level
PG2 isolated from Astragalus membranaceus¹⁰¹	Inhibited the expression of PD-L1 on the cell surface by the protein kinase B (AKT)/mammalian target of rapamycin (mTOR)/ribosomal protein S6 kinase beta-1 (p70S6K) pathway
Indirubin, an active ingredient of Indigofera tinctoria L.¹⁰²	Repaired the expression of PD1 and phosphatase and tensin homolog (PTEN) on the CD4⁺ T cells of ITP patients
PSORI-CM02 consisting of five herbs (Curcumae Rhizoma, Radix Paeoniae Rubra, Rhizoma Smilacis Glabrae, Mume Fructus, and Sarcandrae Herba)¹⁰³	Increased CD8⁺CD122⁺PD-1⁺ Treg frequency in vivo Inhibited mTOR and NF-κB signaling pathways in vitro
Damingyin, an herb formulation¹⁰⁴	Improved visual acuity of patients with proliferative diabetic retinopathy by inhibiting the expression of PD1/PD-L1, then repaired the function of monocytes
Yin Zi Huang, an herbal medicine¹⁰⁵	Inhibited the expression of CD25, CD69, PD-1, and ICOS by stimulated CD4⁺ T cells in mouse