Verification of the expression trend and interaction prediction of innate immune cells and immune-checkpoint molecules in the process of oral mucosal carcinogenesis

doi:10.7518/hxkq.2024.2023280

Abstract

Abstract:

Objective This study aimed to explore the expression trends of innate immune cells and immune-checkpoint molecules validated by data calculation in the process of oral mucosal carcinogenesis, as well as to explore methods of suppressing oral mucosal carcinogenesis based on immunotherapy by predicting their interactions. Me-thods　1) The cancer genome atlas (TCGA) database comprehensively scores immune cells and immune-checkpoint molecules in the process of oral mucosal carcinogenesis and screens out intrinsic immune cells and immune-checkpoint molecules that interfere with tumor immune escape. 2) Clinical patient blood routine data were collected for the statistical analysis of peripheral blood immune cells during the progression of oral mucosal carcinogenesis. Immune cells in peripheral blood that may affect the progression of oral mucosal carcinogenesis were screened. 3) Immunohistochemical staining was performed on intrinsic immune cells and immune-checkpoint molecules validated based on data calculation in various stages of oral mucosal carcinogenesis. 4) Special staining was used to identify innate immune cells in various stages of oral mucosal carcinogenesis based on data-calculation verification. 5) Survival analysis was conducted on intrinsic immune cells and immune-checkpoint molecules validated based on data calculation during the process of oral mucosal carcinogenesis. The association of intrinsic immune cells and immune-checkpoint molecules with the prognosis of oral squamous cell carcinoma was verified. Results The expression of monocytes and neutrophils increased during the process of oral mucosal carcinogenesis. The expression of eosinophils showed a single peak trend of up and down. The expression of mast cells decreased. In the process of oral mucosal carcinogenesis, the expression of the immune-checkpoint molecules cytotoxic T-lymphocyte-associated protein 4 (CTLA4) and programmed cell death-ligand (PD-L1) increased. The expression trends of monocytes, neutrophils, and eosinophils were positively correlated with those of CTLA4 and PD-L1 immune-checkpoint molecules. The expression trend of mast cells was negatively correlated with the expression of CTLA4 and PD-L1. Monocytes, neutrophils, and eosinophils may promote tumor immune escape mediated by CTLA4 and/or PD-L1, thereby accelerating the progression of oral mucosal carcinogenesis. Mast cells may inhibit tumor immune escape mediated by CTLA4 and/or PD-L1, delaying the progression of oral mucosal carcinogenesis. Conclusion Therefore, interference with specific immune cells in innate immunity can regulate the expression of CTLA4 and/or PD-L1 to a certain extent, inhibit tumor immune escape, and delay the progression of oral mucosal carcinogenesis.

Key words: malignant transformation of oral mucosa, immunotherapy, immune escape, inherent immune cells, immune checkpoint molecules

CLC Number:

R739.85

Li Kaiyu, Shi Lijuan, Liu Linxin, Wang Jie, Nie Minhai, Liu Xuqian. Verification of the expression trend and interaction prediction of innate immune cells and immune-checkpoint molecules in the process of oral mucosal carcinogenesis[J]. West China Journal of Stomatology, 2024, 42(2): 192-206.

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分组	性别	例数	年龄/岁	平均年龄/岁
NOM组	男	25	21~71	50.28±3.10
NOM组	女	29	10~72	40.76±3.60
OSCC HD组	男	48	36~98	61.88±1.70
OSCC HD组	女	31	36~92	67.48±2.40
OSCC MD组	男	35	30~77	61.17±2.00
OSCC MD组	女	19	30~83	61.37±3.20
OSCC PD组	男	25	42~79	60.88±2.20
OSCC PD组	女	29	34~87	66.28±2.70

分组	性别	例数	年龄/岁	平均年龄/岁
NOM组	男	1	23	23.00±0.00
	女	1	30	30.00±0.00
OLK ED组	男	3	60~76	68.33±4.60
	女	0	0	0.00±0.00
OSCC HD组	男	0	0	0.00±0.00
	女	4	58~69	63.00±2.30
OSCC MD组	男	2	60~74	67.00±7.00
	女	2	49~69	59.00±10.00
OSCC PD组	男	2	50~67	58.50±8.50
	女	1	69	69.00±0.00

对比组次	WBC
对比组次	数值/（×10⁹/L）	组间P值
NOM与OSCC HD	6.11与7.06	0.23
NOM与OSCC MD	6.11与6.68	0.23
NOM与OSCC PD	6.11与7.23	0.05
OSCC HD与OSCC MD	7.06与6.68	0.96
OSCC HD与OSCC PD	7.06与7.23	0.37
OSCC MD与OSCC PD	6.68与7.23	0.32

对比组次	单核细胞		单核细胞占比
对比组次	数值/（×10⁹/L）	组间P值	数值/%	组间P值
NOM与OSCC HD	0.36与0.40	0.47	5.93与6.12	0.83
NOM与OSCC MD	0.36与0.40	0.32	5.93与6.20	0.96
NOM与OSCC PD	0.36与0.40	0.33	5.93与5.86	0.88
OSCC HD与OSCC MD	0.40与0.40	0.73	6.12与6.20	0.88
OSCC HD与OSCC PD	0.40与0.40	0.86	6.12与5.86	0.60
OSCC MD与OSCC PD	0.40与0.40	0.98	6.20与5.86	0.53

对比组次	嗜酸性粒细胞		嗜酸性粒细胞占比
对比组次	数值/（×10⁹/L）	组间P值	数值/%	组间P值
NOM与OSCC HD	0.15与0.11	0.00	2.41与1.67	0.00
NOM与OSCC MD	0.15与0.11	0.03	2.41与1.81	0.01
NOM与OSCC PD	0.15与0.10	0.00	2.41与1.63	0.00
OSCC HD与OSCC MD	0.11与0.11	0.43	1.67与1.81	0.49
OSCC HD与OSCC PD	0.11与0.10	0.88	1.67与1.63	0.66
OSCC MD与OSCC PD	0.11与0.10	0.37	1.81与1.63	0.32