口腔黏膜癌变进程中固有免疫细胞与免疫检查点分子表达趋势验证及交互作用预测

doi:10.7518/hxkq.2024.2023280

华西口腔医学杂志 ›› 2024, Vol. 42 ›› Issue (2): 192-206.doi: 10.7518/hxkq.2024.2023280

口腔黏膜癌变进程中固有免疫细胞与免疫检查点分子表达趋势验证及交互作用预测

李凯玉(), 石丽娟, 刘林鑫, 王杰, 聂敏海(), 刘旭倩()

西南医科大学附属口腔医院牙周黏膜病科；西南医科大学口颌面修复重建和再生泸州市重点实验室，泸州 646000

收稿日期:2023-08-29 修回日期:2024-01-22 出版日期:2024-04-01 发布日期:2024-03-26
通讯作者: 聂敏海,刘旭倩 E-mail:17860751351@163.com;nieminhai@126.com;liuxuqiankokky@126.com
作者简介:李凯玉，硕士，E-mail：17860751351@163.com
基金资助:
四川省科技计划项目(2022NSFSC0716);泸州市科学技术和人才工作局科技创新领军人才计划(2023RCX171);大学生创新创业训练计划(S202310632340);西南医科大学口腔医学院导师组能力提升计划(2023DS12)

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

Li Kaiyu(), Shi Lijuan, Liu Linxin, Wang Jie, Nie Minhai(), Liu Xuqian()

Dept. of Periodontal Mucosal Diseases, The Affiliated Stomatological Hospital, Southwest Medical University; Luzhou Key Laboratory of Oral＆Maxillofacial Reconstruction and Regeneration, Southwest Medical University, Luzhou 646000, China

Received:2023-08-29 Revised:2024-01-22 Online:2024-04-01 Published:2024-03-26
Contact: Nie Minhai,Liu Xuqian E-mail:17860751351@163.com;nieminhai@126.com;liuxuqiankokky@126.com
Supported by:
Sichuan Provincial Science and Technology Plan Project(2022NSFSC0716);Luzhou Municipal Bureau of Science, Technology and Talent Work Science and Technology Innovation Leading Talent Plan(2023-RCX171);College Student Innovation and Entrepreneurship Training Program(S202310632340);Southwest Me-dical University School of Stomatology Mentor Group Capability Enhancement Plan(2023DS12)

摘要/Abstract

摘要：

目的研究口腔黏膜癌变进程中基于数据计算验证的固有免疫细胞和免疫检查点分子的表达趋势，并通过预测其交互作用，探索免疫治疗抑制口腔黏膜癌变进程的方法。方法 1）利用癌症基因组图谱对口腔黏膜癌变进程中的免疫细胞和免疫检查点分子进行全面评分，筛选出干扰肿瘤细胞免疫逃逸的固有免疫细胞和免疫检查点分子；2）收集血常规资料，对口腔黏膜癌变进程中外周血免疫细胞进行统计学分析，筛选外周血中可能影响口腔黏膜癌变进程的免疫细胞；3）对口腔黏膜癌变进程各阶段中基于数据计算验证的固有免疫细胞和免疫检查点分子进行免疫组织化学染色；4）采用特殊染色鉴定口腔黏膜癌变进程各阶段中基于数据计算验证的固有免疫细胞；5）对口腔黏膜癌变进程中基于数据计算验证的固有免疫细胞和免疫检查点分子进行生存分析，验证固有免疫细胞和免疫检查点分子与口腔鳞状细胞癌预后间的关联。结果在口腔黏膜癌变进程中，单核细胞、中性粒细胞表达呈上升趋势；嗜酸性粒细胞表达呈升降单峰趋势；肥大细胞表达呈下降趋势；免疫检查点分子细胞毒性T淋巴细胞相关蛋白4（CTLA4）和细胞程序性死亡-配体1（PD-L1）的表达呈上升趋势。单核细胞、中性粒细胞和嗜酸性粒细胞表达趋势与CTLA4和PD-L1免疫检查点分子的表达趋势正相关；肥大细胞表达趋势与CTLA4和PD-L1免疫检查点分子的表达趋势负相关。单核细胞、中性粒细胞和嗜酸性粒细胞可能促进CTLA4和（或）PD-L1介导的肿瘤细胞免疫逃逸，加速口腔黏膜癌变进程；肥大细胞可能抑制CTLA4和（或）PD-L1介导的肿瘤细胞免疫逃逸，延缓口腔黏膜癌变进程。结论干扰固有免疫中特定免疫细胞可在一定程度上调控CTLA4和（或）PD-L1的表达，抑制肿瘤细胞免疫逃逸，延缓口腔黏膜癌变进程。

关键词: 口腔黏膜癌变, 免疫治疗, 免疫逃逸, 固有免疫细胞, 免疫检查点分子

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

中图分类号:

R739.85

李凯玉, 石丽娟, 刘林鑫, 王杰, 聂敏海, 刘旭倩. 口腔黏膜癌变进程中固有免疫细胞与免疫检查点分子表达趋势验证及交互作用预测[J]. 华西口腔医学杂志, 2024, 42(2): 192-206.

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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参考文献 46

1	王海青, 向婉婷, 卢俊米. PD-L1在口腔鳞状细胞癌中表达的临床意义[J]. 中国卫生标准管理, 2023, 14(6): 83-87.
	Wang HQ, Xiang WT, Lu JM. Clinical significance of PD-L1 expression in oral squamous cell carcinoma[J]. China Health Stand Manag, 2023, 14(6): 83-87.
2	Koike K, Dehari H, Ogi K, et al. Prognostic value of FoxP3 and CTLA-4 expression in patients with oral squamous cell carcinoma[J]. PLoS One, 2020, 15(8): e-0237465.
3	Wu T, Tang C, Tao R, et al. PD-L1-mediated immunosuppression in oral squamous cell carcinoma: relationship with macrophage infiltration and epithelial to mesenchymal transition markers[J]. Front Immunol, 2021, 12: 693881.
4	Sudo S, Kajiya H, Okano S, et al. Cisplatin-induced programmed cell death ligand-2 expression is associated with metastasis ability in oral squamous cell carcinoma[J]. Cancer Sci, 2020, 111(4): 1113-1123.
5	Yuan Y, Jiao P, Wang Z, et al. Endoplasmic reticulum stress promotes the release of exosomal PD-L1 from head and neck cancer cells and facilitates M2 macropha-ge polarization[J]. Cell Commun Signal, 2022, 20(1): 12.
6	Weber M, Lutz R, Olmos M, et al. Beyond PD-L1-identification of further potential therapeutic targets in oral cancer[J]. Cancers (Basel), 2022, 14(7): 1812.
7	Yu GT, Bu LL, Zhao YY, et al. CTLA4 blockade reduces immature myeloid cells in head and neck squamous cell carcinoma[J]. Oncoimmunology, 2016, 5(6): e1151594.
8	Starzyńska A, Sejda A, Adamski Ł, et al. The B7 family molecules in oral squamous cell carcinoma: a systematic review. PartⅠ: B7-H1 (PD-L1) and B7-DC (PD-L2)[J]. Postepy Dermatol Alergol, 2022, 39(2): 265-274.
9	Badoual C, Hans S, Merillon N, et al. PD-1-expressing tumor-infiltrating T cells are a favorable prognostic biomarker in HPV-associated head and neck cancer[J]. Cancer Res, 2013, 73(1): 128-138.
10	Zgodzinski W, Grywalska E, Zinkiewicz K, et al. Peripheral blood T lymphocytes are downregulated by the PD-1/PD-L1 axis in advanced gastric cancer[J]. Arch Med Sci, 2019, 15(3): 774-783.
11	Quan J, Morrison NA, Johnson NW, et al. MCP-1 as a potential target to inhibit the bone invasion by oral squamous cell carcinoma[J]. J Cell Biochem, 2014, 115(10): 1787-1798.
12	Moradi Tabriz H, Obohat M, Vahedifard F, et al. Survey of mast cell density in transitional cell carcinoma[J]. I-ran J Pathol, 2021, 16(2): 119-127.
13	Hadjigol S, Shah BA, O’Brien-Simpson NM. The ‘Danse Macabre’-neutrophils the interactive partner affec-ting oral cancer outcomes[J]. Front Immunol, 2022, 13: 894021.
14	Siddiqui S, Jaiswal R, Hashmi GS. Quantitative analysis of tumor-associated tissue eosinophils and tumor-associated blood eosinophils in oral squamous cell carcinoma[J]. J Oral Maxillofac Pathol, 2020, 24(1): 131-137.
15	Sharma HD, Mahadesh J, Monalisa W, et al. Quantitative assessment of tumor-associated tissue eosinophilia and nuclear organizing region activity to validate the significance of the pattern of invasion in oral squamous cell carcinoma: a retrospective study[J]. J Oral Maxillofac Pathol, 2021, 25(2): 258-265.
16	李腾艳, 聂敏海, 陈潇, 等. 白细胞表达趋势在监测癌前病损和OSCC早期诊断中的价值研究[J]. 实用口腔医学杂志, 2020, 36(5): 753-757.
	Li TY, Nie MH, Chen X, et al. The value of leukocyte expression trend in monitoring precancerous lesion and early diagnosis of OSCC[J]. J Pract Stomatol, 2020, 36(5): 753-757.
17	高岩. 口腔组织病理学[M]. 北京: 人民卫生出版社, 2020: 81-90, 181-182, 315-319.
	Gao Y. Oral histology and pathology[M]. Beijing: People’s Medical Publishing House, 2020: 81-90, 181-182, 315-319.
18	Marin-Acevedo JA, Kimbrough EO, Lou Y. Next gene-ration of immune checkpoint inhibitors and beyond[J]. J Hematol Oncol, 2021, 14(1): 45.
19	Shi L, Yang Y, Li M, et al. LncRNA IFITM4P promotes immune escape by up-regulating PD-L1 via dual mechanism in oral carcinogenesis[J]. Mol Ther, 2022, 30(4): 1564-1577.
20	Phulari RGS, Rathore RS, Shah AK, et al. Neutrophil: lymphocyte ratio and oral squamous cell carcinoma: a preliminary study[J]. J Oral Maxillofac Pathol, 2019, 23(1): 78-81.
21	Grimm M, Rieth J, Hoefert S, et al. Standardized pretreatment inflammatory laboratory markers and calculated ratios in patients with oral squamous cell carcinoma[J]. Eur Arch Otorhinolaryngol, 2016, 273(10): 3371-3384.
22	Teófilo CR, Ferreira Junior AEC, Batista AC, et al. Mast cells and blood vessels profile in oral carcinogenesis: an immunohistochemistry study[J]. Asian Pac J Cancer Prev, 2020, 21(4): 1097-1102.
23	Ansari FM, Asif M, Kiani MN, et al. Evaluation of mast cell density using CD117 antibody and microvessel density using CD34 antibody in different grades of oral squa-mous cell carcinoma[J]. Asian Pac J Cancer Prev, 2020, 21(12): 3533-3538.
24	Narayan KV, Sonia G, Shrestha P, et al. A comparative study of mast cells count in different histological grades of oral squamous cell carcinoma by using toluidine blue stain[J]. Cureus, 2020, 12(9): e10626.
25	Ingaleshwar PS, Pandit S, Desai D, et al. Immunohistochemical analysis of angiogenesis by CD34 and mast cells by toluidine blue in different grades of oral squamous cell carcinoma[J]. J Oral Maxillofac Pathol, 2016, 20(3): 467-473.
26	Lien MY, Chang AC, Tsai HC, et al. Monocyte chemoattractant protein 1 promotes VEGF-A expression in OSCC by activating ILK and MEK1/2 signaling and downregulating miR-29c[J]. Front Oncol, 2020, 10: 592415.
27	Gao L, Wang FQ, Li HM, et al. CCL2/EGF positive feedback loop between cancer cells and macrophages promotes cell migration and invasion in head and neck squamous cell carcinoma[J]. Oncotarget, 2016, 7(52): 87037-87051.
28	Debta P, Debta FM, Chaudhary M, et al. Evaluation of myeloid cells (tumor-associated tissue eosinophils and mast cells) infiltration in different grades of oral squamous cell carcinoma[J]. Indian J Med Paediatr Oncol, 2016, 37(3): 158-167.
29	Sahni P, Patel A, Md S, et al. Tumor associated tissue eosinophilia in oral squamous cell carcinoma: a histo-che-mical analysis[J]. Malays J Med Sci, 2015, 22(6): 21-25.
30	Goertzen C, Mahdi H, Laliberte C, et al. Oral inflammation promotes oral squamous cell carcinoma invasion[J]. Oncotarget, 2018, 9(49): 29047-29063.
31	Oliveira-Costa JP, de Carvalho AF, da Silveira da GG, et al. Gene expression patterns through oral squamous cell carcinoma development: PD-L1 expression in primary tumor and circulating tumor cells[J]. Oncotarget, 2015, 6(25): 20902-20920.
32	Hirai M, Kitahara H, Kobayashi Y, et al. Regulation of PD-L1 expression in a high-grade invasive human oral squamous cell carcinoma microenvironment[J]. Int J Oncol, 2017, 50(1): 41-48.
33	Kämmerer PW, Toyoshima T, Schöder F, et al. Association of T-cell regulatory gene polymorphisms with oral squamous cell carcinoma[J]. Oral Oncol, 2010, 46(7): 543-548.
34	Weber M, Wehrhan F, Baran C, et al. Prognostic significance of PD-L2 expression in patients with oral squamous cell carcinoma—A comparison to the PD-L1 expression profile[J]. Cancer Med, 2019, 8(3): 1124-1134.
35	Jiang M, Li B. STAT3 and its targeting inhibitors in oral squamous cell carcinoma[J]. Cells, 2022, 11(19): 3131.
36	Shrestha A, Keshwar S, Raut T. Evaluation of mast cells in oral potentially malignant disorders and oral squamous cell carcinoma[J]. Int J Dent, 2021, 2021: 5609563.
37	Wu MH, Hong HC, Hong TM, et al. Targeting galectin-1 in carcinoma-associated fibroblasts inhibits oral squamous cell carcinoma metastasis by downregulating MCP-1/CCL2 expression[J]. Clin Cancer Res, 2011, 17(6): 1306-1316.
38	Verza FA, Valente VB, Oliveira LK, et al. Social isolation stress facilitates chemically induced oral carcinogenesis[J]. PLoS One, 2021, 16(1): e0245190.
39	Yellapurkar S, Natarajan S, Boaz K, et al. Tumour-associated tissue eosinophilia in oral squamous cell carcinoma—A boon or a bane[J]. J Clin Diagn Res, 2016, 10(4): ZC65-ZC68.
40	陈晓琳, 杨于权, 侯照远, 等. 肿瘤相关中性粒细胞在肿瘤免疫治疗中的研究进展[J]. 中国免疫学杂志, 2023, 39(7): 1519-1524.
	Chen XL, Yang YQ, Hou ZY, et al. Role of tumor-associated neutrophils in tumor immunotherapy[J]. Chin J Immunol, 2023, 39(7): 1519-1524.
41	Wu CF, Hung TT, Su YC, et al. Endoplasmic reticulum stress of oral squamous cell carcinoma induces immunosuppression of neutrophils[J]. Front Oncol, 2022, 12: 818192.
42	Hu X, Xiang F, Feng Y, et al. Neutrophils promote tumor progression in oral squamous cell carcinoma by regulating EMT and JAK2/STAT3 signaling through che-merin[J]. Front Oncol, 2022, 12: 812044.
43	Dong Y, Wang Z, Mao F, et al. PD-1 blockade prevents the progression of oral carcinogenesis[J]. Carcinogenesis, 2021, 42(6): 891-902.
44	陈志红, 吴亚东. 程序性死亡受体-1及其配体在口腔鳞状细胞癌中的研究进展[J]. 华西口腔医学杂志, 2020, 38(4): 449-453.
	Chen ZH, Wu YD. Development of programmed death receptor-1 and programmed death receptor-1 ligand in o-ral squamous cell carcinoma[J]. West China J Stomatol, 2020, 38(4): 449-453.
45	Suárez-Sánchez FJ, Lequerica-Fernández P, Suárez-Canto J, et al. Macrophages in oral carcinomas: relationship with cancer stem cell markers and PD-L1 expression[J]. Cancers (Basel), 2020, 12(7): 1764.
46	Kai K, Moriyama M, Haque ASMR, et al. Oral squamous cell carcinoma contributes to differentiation of mo-nocyte-derived tumor-associated macrophages via PAI-1 and IL-8 production[J]. Int J Mol Sci, 2021, 22(17): 9475.

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

口腔黏膜癌变进程中固有免疫细胞与免疫检查点分子表达趋势验证及交互作用预测

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

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对比组次	嗜碱性粒细胞		嗜碱性粒细胞占比
对比组次	数值/（×10⁹/L）	组间P值	数值/%	组间P值
NOM与OSCC HD	0.02与0.03	0.14	0.39与0.44	0.32
NOM与OSCC MD	0.02与0.02	0.40	0.39与0.39	0.69
NOM与OSCC PD	0.02与0.03	0.20	0.39与0.42	0.58
OSCC HD与OSCC MD	0.03与0.02	0.64	0.44与0.39	0.56
OSCC HD与OSCC PD	0.03与0.03	0.93	0.44与0.42	0.63
OSCC MD与OSCC PD	0.02与0.03	0.71	0.39与0.42	1.00

对比组次	中性粒细胞		中性粒细胞占比
对比组次	数值/（×10⁹/L）	组间P值	数值/%	组间P值
NOM与OSCC HD	3.71与5.00	0.05	67.65与68.12	0.80
NOM与OSCC MD	3.71与4.50	0.03	67.65与66.83	0.70
NOM与OSCC PD	3.71与5.09	0.00	67.65与67.65	1.00
OSCC HD与OSCC MD	5.00与4.50	0.50	68.12与66.83	0.47
OSCC HD与OSCC PD	5.00与5.09	0.79	68.12与67.65	0.80
OSCC MD与OSCC PD	4.50与5.09	0.41	66.83与67.65	0.69