Table 2.

The potential biomarkers in HNSCC immune TME and their advantages and disadvantages.

Potential Biomarker		Method	Functions	Advantages	Disadvantages
TMB		Sequencing	Reflect neoantigen level	Clonal TME was the most powerful predictor of ICI response by pan-cancer analysis	Need verification in untreated HNSCC
IRGPI	SFRP4/CPXM1/COL5A1	Sequencing	Positive with active immune	IRGPI-high group tended to benefit more from ICI therapy	Predicting method TIDE was trained by R/M HNSCC
Exosome	TSP1	Sequencing	Polarization of M1	Responsible for cancer stage and lymph node metastasis	Relationship between exosomes and distant metastasis is controversial
	PD-L1		Immune checkpoint inhibitor
	miR-196a		Corresponded with OS and drug resistance	Considerable prediction effect
Peripheral Blood	NLR	Blood Test	Reflect the degree of specific immunity	Increased NLR with shorter OS	Its role in HNSCC immunotherapy needs verification
	Eosinophil		A role of immune TME	Potential for predicting the tumor recurrence
CTLA-4		Sequencing	Inhibit APC and T cell activation	CTLA-4 inhibitor treatment enhanced immunotherapy	Need verification in HNSCC
MTAP		Sequencing	Break down methylthioadenosine and expression of Toll-like receptor and JAK-STAT signal pathway	predict the low response rate of immune therapy	Limited samples and Need verification in untreated HNSCC