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.