Table 1.

Differences between HPV^+ve and HPV^−ve HNSCC TME

Serial No.	Cell type	HPV status	Levels in tumor	Protein expression/factors secreted	Prognosis	Ref.
1	CD3+	HPV+ve	Higher	IFN-γ	Better	64
2	CD4+		Higher	IFN-γ, TNF-α	Better	65
3	CD8+		Higher	IFN-γ, IL-17	Better	64
4	CD4+/CD8+ ratio		Lower		Better	74
5	CD4+CD25+ Tregs		Higher	IL-10, IL-12, IL-35, TGF-β, VEGF	Better	71
6	CD56+ NK cells		Higher	IFN-γ,	Better	71
7	M1 macrophages		Lower	IL-12, IL-23, TNF-α, CCL5, CXCL9, CXCL5, CXCL10	Better	74
8	M2 macrophages		Higher	TGF-β, IL-13, IL-4, IL-10, MMP9, CCL2, CCL5, CXCL2, CXCL8, MIF, EGF, VEGF, ROS, arginase-1	Poor	72
9	MDSCs		Higher	iNOS, NO, ROS, MMP9, PD-L1, arginase-1	Poor	70
10	CD45+ lymphocytes		Higher		Better	54
11	CD19+/CD20+ B cells		Higher		Better	54
12	Tumor-infiltrating APCs		Higher	--	Better	70
13	Langerhans cells		Higher	--	Better	70
14	Chemokines		Higher	IL-10, CCL2, EGF	Poor	55,56
15	Cytotoxic mediators		Higher	Granzyme A, granzyme B, perforin	Better	53,76
16	Protein molecules		Lower	E-cadherin, MIP-3, IFN-γ, MHC1 CD1d	Poor	79,81,85
			Higher	LAG3, PD-1, TIGIT, TIM3, CD39, COX2, PD-L1, PD-L2	Poor	202,238
17	Metabolism Core Periphery	HPV-ve	Higher Higher	Aerobic glycolysis OXPOS	Poor	28
18	Metabolic mediators Core Periphery		Lower Higher	GLUT1, MCT1, COX5B, and LDHB	Poor	28

Tregs T regulatory cells, NK cells natural killer cells, MDSCs myeloid-derived suppressor cells, APC antigen-presenting cells, MIP-3 macrophage inflammatory protein 3, Tim-3 T-cell immunoglobulin and mucin domain-3, LAG3 lymphocyte-activation gene 3, PD-1 programmed death-1, TIGIT T-cell immune receptor with Ig and ITIM domains, GLUT1 glucose transporter-1, LDHB lactate dehydrogenase-B, MCT1 monocarboxylase transporter 1, COX2 cyclooxygenase-2, COX5B cyclooxygenase 5B, OXPHOS oxidative phosphorylation