Table 1.

The advantages and disadvantages of murine models for immunotherapy studies of hepatocellular carcinoma (HCC).

Mouse Model		Advantages	Disadvantages	Reference
Syngeneic		• Not artificial	• Lack of diverse cancer cell line and heterogeneity	[15,17,18,19,20,21,22]
		• Easy to utilize	• Mostly chemical induced cancer cell line
		• Rapid tumor development	• Tumor does not develop from normal cells or develop in a natural microenvironment
		• Reproducible	• Mouse and human immune systems have vital differences
		• Low in cost	• Might cause a vaccination effect
		• Tumor can be accurately monitored without difficulty	• Human HCC cannot be completely recapitulated by mouse cancer cells in terms of the complexity, histology, and natural carcinogenesis characteristics
		• Non-immunogenic	• Short experimental window
Chemotoxic agent		• Easy to work with	• Tumor formation is not initiated by chronic inflammation	[18,19,20,21,23]
		• Sporadic cancer development
		• Higher heterogeneity	• Difficult to monitor a tumor
		• Tumors generally progress in a natural microenvironment and develop from normal cells	• Variability in the time for tumor progression
		• Available to incorporate with other approaches for tumor induction	• Larger sample sizes are needed for data interpretation due to the high heterogeneity
GEMM		• Encompasses natural tumor microenvironments	• Longer latency and time for tumor development	[15,17,18,19,20,21,22]
		• The genetic and histopathological aspects of all stages of cancer can be recapitulated	• Difficult to monitor a tumor
			• Low immunogenicity
			• Costly and challenging for breeding and gene manipulation
		• Tumors develop from normal cells	• Homogeneous in the genomic aspect
Humanized	CD34+	• Immediately available for experiment	• 4–8 weeks of experimental window	[15,21,24,25]
		• The complex human immune system and human HCC can be recapitulated	• Difficult to set up
	PBL	• The entire complex human immune system can be established	• 10-12 weeks are required for HSC engraftment	[15,21,24,25]
			• Difficult to set up
		• Human HCC can be recapitulated	• High in cost