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Table 1 The basic research on TCM enhances the efficacy of ICIs

From: Traditional Chinese medicine in the era of immune checkpoint inhibitor: theory, development, and future directions

Cancers (cells)

Type

TCM

Formulation

ICIs

Upregulate

Downregulate

References

Mechanism: regulation of tumor microenvironment

 Colon carcinoma (CT26)

In vivo and in vitro

Andrographis paniculata

Monomer

Anti-PD-1

CD4 + and CD8 + T cells, IFN-γ, and granzyme B + 

COX2 and PGE2

Liu W et al. [79]

 Colon carcinoma (MC38)

In vivo and in vitro

Sanguisorbae Radix

Extract

Anti-PD-1

CD8 + T cells

NA

Lee EJ et al. [86]

 Colon carcinoma (CMT93 and HCT116)

In vivo and in vitro

Pien-Tze-Huang

Compound prescription

Anti-PD-1 and anti-PD-L1

CD3 + and CD8 + T cells, IFN-γ, and granzyme B +

p-STAT3, IRF1, and PD-L1 expression

Chen Q et al. [88]

 Colon carcinoma (CT26) and breast cancer (4T1)

In vivo

Ginseng-derived nanoparticles

Monomer

Anti-PD-1

CD4 + and CD8 + T cells, CCL5, CXCL9, granzyme B + , IFN-γ, TNF-α, and IL-2

M2/M1 ratio

Han X et al. [84]

 Colon carcinoma (MC38)

In vivo

Dahuang Fuzi Baijiang decoction

Compound prescription

Anti-PD-1

CD8 + T and PD-1int T cells

PD-1hiTim3 + Tex

Xu Y et al. [83]

 Colon carcinoma (MC38)

In vivo

Atractylenolide I

Monomer

Anti-PD-1

CD8 + T cells

NA

Xu H et al. [85]

 Breast cancer (4T1 or MDA-MB-231)

In vivo

Salvianolic acid B

Monomer

Anti-PD-L1

CD8 + T cells, granzyme B + , IFN-γ

PD-1 expression

Qian C et al. [91]

 Melanoma (B16F10) and colon carcinoma (MC38) and

In vivo and in vitro

Icaritin

Monomer

Anti-PD-1 and anti-CTLA-4

CD8 + T cells

PD-L1 expression on MDSCs and neutrophils

Hao H et al. [93]

 Melanoma (B16-F10)

In vivo and in vitro

Ailanthone

Monomer

Anti-PD-L1

CD4 + and CD8 + T cells, granzyme B + , IFN-γ, M1

Tregs, M2, MDSCs, and PD-L1 expression

Yu P et al. [94]

 Lung cancer (A549 or lewis lung carcinoma)

In vivo and in vitro

Cryptotanshinone

Monomer

Anti-PD-L1

CD4 + and CD8 + T cells, CXCL9, CXCL11, granzyme B + , IFN-γ, and perforin

DCs (CD11c + /CD45 +)

Liu S et al. [90]

 Ovarian cancer (JHOC-5), colon cancer (MC38 or CT26)

In vivo and in vitro

Curcumin

Monomer

Anti-PD-1 and anti-PD-L1

CD8 + T cells, IFN-γ, DCs in the dLNs and spleens

STAT3 and IL-6

Hayakawa T et al. [95]

 Hepatocellular carcinoma (Hepa1-6)

In vivo

Bufalin

Monomer

Anti-PD-1

CD4 + and CD8 + T cells, macrophage, IFN-γ, TNF-α, and IL-10

M2 phenotype, p50 NF-κB, and TGF-β

Yu Z et al. [96]

Mechanism: modulation of gut microbiota

 Colon carcinoma (CT26)

In vivo

Gegen Qinlian decoction

Compound prescription

Anti-PD-1

s__Bacteroides_acidifaciens, s__uncultured_organism_g__norank_f__Bacteroidales_S24-7_group, CD8 + T cells, IL-1, and IFN-γ

CD4 + T cells

Lv J et al. [81]

 Colon carcinoma (MC38)

In vivo

Jujube powder

TCM

Anti-PD-L1

Diversity index of gut microbiota, and Lachnospiraceae

Prevotellaceae

Wang L et al. [80]

 Lung cancer (lewis lung cancer) and melanoma (B16-F10)

In vivo

Ginseng polysaccharides

Monomer

Anti-PD-1

Diversity index of gut microbiota, and Bacteroides (B. vulgatus and P. distasonis), CD8 + T cells, granzyme B + , IFN-γ, TNF-α, and SCFAs abundance

Treg cells, IDO activity, kynurenine/tryptophan ratio

Huang J et al. [89]

Mechanism: others

 Melanoma (B16)

In vivo and in vitro

Juzentaihoto

Compound prescription

Anti-PD-1

IL-12, IFN-γ, and NKs activity

NA

Ishikawa S et al. [93]

 Colon carcinoma (CT26)

In vivo and in vitro

Jiedu Sangen decoction

Compound prescription

Anti-PD-L1

E-cadherin

N-cadherin, β-actin, Slug, Snail, Vimentin, PI3K, P-AKT, and AKT

Shan F et al. [82]

 Melanoma (B16F10)

In vivo

Astragalus membranaceus polysaccharides

Monomer

Anti-PD-L1

NKs, IFN-γ, CD4 + and CD8 + T cells in mesenteric lymph nodes and lung

B16 cells

Hwang J et al. [92]

 Acute T lymphoblastic leukemia (Jurkat cells)

In vitro

YIV-906 (inspired by Huang Qin Tang)

Compound prescription

Anti-PD-1

Nuclear factor of activated T cells activity

NA

Lam W et al. [97]

  1. TCM traditional Chinese medicine, ICIs immune checkpoint inhibitors, PD-1 programmed death-1, IFN-γ interferon-γ, COX2 cyclooxygenase-2, PGE2 prostaglandin E2, NA not available, PD-L1 programmed cell death-ligand 1, p-STAT3 phosphorylated signal transducer and activator of transcription 3, IRF1 interferon regulatory factor 1,CCL5 chemokine (C-C motif) ligand 5, CXCL9 chemokine (C-X-C motif) ligand 9, CXCL11 chemokine (C-X-C motif) ligand 11, TNF-α tumor necrosis factor-α, IL-2 interleukin-2, M2 macrophages 2, M1 macrophages 1, PD-1int T cells intermediate PD-1 expression, PD-1hiTim3 + Tex T-cell immunoglobulin domain and mucin domain 3 + subset with intermediate expression of PD-1, MDSCs myeloid-derived suppressor cells, Tregs regulatory cells, DCs dendritic cells, dLNs draining lymph nodes, IL-6 interleukin-6, IL-10 interleukin-10, p50 NF-κB nuclear factor kappa-B1, TGF-β tumor necrosis factor-β, IL-1 interleukin-1, SCFAs short chain fatty acids, IDO indole-3-pyruvate, IL-12 interleukin-12, NKs natural killer cells, PI3K phosphoinositide-3 kinase, P-AKT phosphorylated protein kinase B