Pair Name	Vitamin C, Anti-PD-1 antibody
Partner Name	Vitamin C
Disease Info	[ICD-11: 2B33.5]	Lymphoma		Investigative
Biological Phenomena	Inhibition-->Anti-PD1 checkpoint
Gene Regulation	Up-regulation	Expression	GZMB	hsa3002
	Up-regulation	Expression	IL12B	hsa3593
In Vitro Model	A20	Reticulum cell sarcoma	Mus musculus (Mouse)	CVCL_1940
	SU-DHL-6	Diffuse large B-cell lymphoma germinal center B-cell type	Homo sapiens (Human)	CVCL_2206
	OCI-Ly1	Diffuse large B-cell lymphoma	Homo sapiens (Human)	CVCL_1879
	OCI-Ly7	Diffuse large B-cell lymphoma germinal center B-cell type	Homo sapiens (Human)	CVCL_1881
	OCI-Ly3	Diffuse large B-cell lymphoma activated B-cell type	Homo sapiens (Human)	CVCL_8800
In Vivo Model	40 BALB/c mice received a subcutaneous (s.c.) right flank injection of 5×10⁶ A20 tumor cells in phosphate-buffered saline (PBS) and were randomly assigned to 4 groups of 10 mice: vehicle, anti-PD1 (α-PD1), AA, and AA+α-PD1.
Result	This study shows that AA treatment 1) increases immunogenicity of lymphoma cells; 2) enhances intratumoral infiltration of CD8+ T cells and macrophages; and 3) synergizes with anti-PD1 checkpoint inhibition in a syngeneic lymphoma mouse model via marked activation of cytotoxic cells (cytotoxic T cells and NK cells) and antigen presenting cells. The data provide a compelling rationale for testing combinations of high-dose AA and anti-PD1 agents in patients with aggressive B cell lymphoma and in preclinical models of other malignancies.

Pair Name	Quercetin, Anti-PD-1 antibody
Partner Name	Quercetin
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Reshaped-->Tumor immune microenvironment
Gene Regulation	Up-regulation	Expression	ARG1	hsa383
	Up-regulation	Expression	CD4	hsa920
	Up-regulation	Expression	CD8A	hsa925
	Up-regulation	Expression	IFNG	hsa3458
	Up-regulation	Expression	IL10	hsa3586
	Down-regulation	Expression	IL12A	hsa3592
	Down-regulation	Expression	IL1B	hsa3553
	Down-regulation	Expression	IL4	hsa3565
	Down-regulation	Expression	IL6	hsa3569
	Up-regulation	Expression	ITGAM	hsa3684
	Up-regulation	Expression	MMP9	hsa4318
	Down-regulation	Expression	NFKBIA	hsa4792
	Down-regulation	Expression	RELA	hsa5970
	Up-regulation	Expression	TGFB1	hsa7040
	Down-regulation	Expression	TLR4	hsa7099
	Down-regulation	Expression	TNF	hsa7124
In Vivo Model	Orthotopically transplanted HCC tumors in mice were treated with quercetin, anti-PD-1 antibody, or a combination of both therapies.
Result	Quercetin/anti-PD-1 antibody combination therapy reshaped HCC tumor microenvironment in mice in parallel with regulating the GM and macrophage immunity.

Pair Name	Lycopene, Anti-PD-1 antibody
Partner Name	Lycopene
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Immunomodulatory
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Expression	CXCL10	KEGG ID N.A.
	Up-regulation	Expression	CXCL9	KEGG ID N.A.
	Down-regulation	Expression	DNMT3A	KEGG ID N.A.
	Up-regulation	Expression	IFNG	hsa3458
	Up-regulation	Expression	IRF1	hsa3659
	Up-regulation	Expression	IRF7	KEGG ID N.A.
	Up-regulation	Phosphorylation	JAK2	hsa3717
	Down-regulation	Expression	PD-L1	KEGG ID N.A.
	Up-regulation	Phosphorylation	STAT3	hsa6774
In Vitro Model	3LL	Malignant tumors of the mouse pulmonary system	Mus musculus (Mouse)	CVCL_5653
In Vivo Model	Lewis lung carcinoma (LLC) cells (1×10⁶) were injected in the rear flak of C57BL/6 mice
Result	lycopene promoted anti-PD-1 therapeutic efficiency of lung cancer by promoting IFNγ-expressing CD8+ cells infiltrated in tumor tissues and increasing IFNγ expression in tumor cells.

Pair Name	Curcumin, Anti-PD-1 antibody
Partner Name	Curcumin
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Induction-->Immune evasion
Gene Regulation	Down-regulation	Expression	EP300	hsa2033
	Down-regulation	Activity	SMAD2/3	KEGG ID N.A.
	Down-regulation	Expression	TGFB1	hsa7040
In Vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens (Human)	CVCL_0326
In Vivo Model	Hep3B cells in the logarithmic growth phase were suspended in 50% Matrigel (BD Biosciences) and adjusted to a density of 2×10⁶ cells/mL, and 0.2 mL of single-cell suspension was subcutaneously injected into the left axilla of each mouse.
Result	Synergistic efficacy of curcumin and anti-programmed cell death-1 in hepatocellular carcinoma

Pair Name	Carnosic acid, Anti-PD-1 antibody
Partner Name	Carnosic acid
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Induction-->Immunomodulatory
Gene Regulation	Down-regulation	Expression	CTNNB1	hsa1499
	Down-regulation	Expression	GSK3B	hsa2932
	Down-regulation	Expression	WNT3A	hsa89780
In Vitro Model	MHCC97-H	Adult hepatocellular carcinoma	Homo sapiens (Human)	CVCL_4972
In Vivo Model	MHCC97H cells (4×10⁶ cells/site) were implanted subcutaneously into hip of four- to five-week-old male athymic nude mice.
Result	CA-NBF combined with anti-PD-1 have stronger immunomodulatory and anticancer effects without increasing biological toxicity.