Using Traditional Chinese Medicine to Treat Hepatocellular Carcinoma by Targeting Tumor Immunity

Table 1

Individual drugs or their chemical compounds enhance tumor immunity.

Year	Drug	Source(s) of drug	The mode of administration	Change(s) of signal pathway involved	Change(s) of immune compounds	Ref.
2003; 2017	Cinobufagin	Venenum bufonis	Intravenous (clinical); intraperitoneal administration	Proopiomelanocortin/β-endorphin/μ-opioid receptor pathway	CD3+, CD4+, and CD8+ T cells ↑; IL-1β ↓	[27, 28]
2005; 2012	Lycium barbarum polysaccharide	Goji berry	In vitro; oral	NF-κb pathway↑	IL-12p70 and IFN-γ ↑; DC ↑; CD4+ and CD8+ T cells ↑	[29, 30]
2007	Standardized silymarin extract	Milk thistle	In vitro	NF-κβ pathway ↓; JAK-STAT pathway ↑	TNF-α ↓; CXCL8 transcription ↓; IFN-α ↑	[31]
2009	Ganoderma lucidum polysaccharides	Ganoderma lucidum	Intragastric	None	CD8+ T cells ↑; immunoglobulin A ↑; TNF-α ↑; IL-2 ↑; IL-10 ↓	[32]
2011	Radix Glycyrrhizae polysaccharide	Radix Glycyrrhizae	Intraperitoneal; subcutaneous	Th1-skew immune response ↑; Th2-skew immune response ↓	IL-2 and IL-12p70 ↑; IL-10 and TGF-β ↓	[33]
2011	Strongylocentrotus nudus eggs polysaccharide	Sea urchins	Intraperitoneal	NFAT pathway ↑; MAPK/ERK pathway ↑	CD4+ and CD8+ T lymphocytes ↑; CTL cytotoxicity ↑; serum IgG, IgM, and IgA antibody ↑; IL-2 and TNF-α ↑; Erk1/2 ↑	[34]
2012	Shikonin	Arnebia euchroma; Lithospermum erythrorhizon	By gavage	None	NK, CD3+, and CD19+ T cells ↑; IL-2 ↑	[35]
2012	Dioscorea bulbifera L. extract	Dioscorea bulbifera L.	Intragastric	None	Spleen and thymus weight ↑; total leukocytes, lymphocytes, and neutrophils ↑	[36]
2012	Eupolyphaga sinensis Walker extract	Eupolyphaga sinensis Walker	Intragastric	Th1-skew immune response ↑	TNF-α and IFN-γ ↑	[37]
2012	Astragalus polysaccharides	Astragalus membranaceus	Oral (clinical)	CXCR4/CXCL12 pathway↓	FOXP3+ Treg ↓; SDF-1 ↓	[38]
2013	Gastrodin	Gastrodia elata Blume	Intraperitoneal	Th1-skew immune response ↑; Th2-skew immune response ↓	NK and CD8+ T cells ↑; serum IL-2 and IFN-γ ↑; serum IL-4 ↓	[39]
2013	Xiaoaiping	Marsdenia tenacissima	Intravenous injection (clinical)	None	Peripheral CD3+ and CD4+ T cells ↑	[40]
2014	Corn silk polysaccharides	Corn	Oral	None	Peripheral WBC count ↑; thymus and spleen index ↑; serum IL-2, IL-6, and TNF-α ↑	[41]
2014	Ginsenoside Rg3	Ginseng	Intraperitoneal	None	IL-2 and IFN-γ ↑	[42]
2019	Glycyrrhizin	Radix Glycyrrhizae	Intravenous	Bax/Bcl-2 ↑	Kupffer cells and TAM ↓	[43]
2019	Triterpenoid saponins	Anemone flaccida Fr. Schmidt	Oral	NF-κβ pathway ↓; JNK/STAT pathway ↓; PD-1/PD-L1 pathway	B cells, NK cells, and CD3+/CD28+ T cells ↑; FOXP3+ Tregs ↓; TNF-α, TGF-β, COX-2, and mPGES1 ↓; ERK1/2 and p38 ↓	[44]
2019	Icaritin	Epimedii herba	Oral (clinical)	M1-type macrophages activation↑; M2-type macrophage activation ↓	Total neutrophils ↓; total lymphocytes ↑; MDSC populations ↓; serum IL-6, IL-7, IL-8, IL-10, and IL-15 ↓; serum IFN-γ ↑	[45]

NF-κB: nuclear factor-κB; IL: interleukin; IFN: interferon; JAK-STAT: janus kinase-signal transducer and activator of transcription; TNF: tumor necrosis factor; CXCL : C-X-C motif ligand; CXCR : C-X-C motif receptor; TGF-β: transforming growth factor-β; NFAT: nuclear factor of activated T cells; MAPK/ERK: mitogen-activated protein kinase/extracellular regulated protein kinases; CTL: cytotoxic T lymphocyte; Ig: immunoglobulin; NK: natural killer; CD: cluster of differentiation; Treg: regulatory T cell; SDF-1: stromal cell-derived factor-1; Bax/Bcl : BCL2-associated X/B-cell lymphoma; TAM: tumor-associated macrophage; JNK : Jun N-terminal kinase; PD: programmed cell death; COX: cyclooxygenase; mPGES: membrane associated prostaglandin E synthase; MDSC: myeloid-derived suppressor cells.