Clinical analysis of immune function, intestinal flora changes in patients with oral squamous carcinoma before, after treatment

doi:10.19439/j.sjos.2022.05.014

Abstract

Abstract: PURPOSE: To characterize the alterations of intestinal bacteria and immunological function in patients with oral squamous cell carcinoma(OSCC) before and after treatment. METHODS: From September 2020 to September 2021, 28 patients suffering OSCC and 10 healthy volunteers undergoing treatment at our hospital were enrolled in the study. Conventional treatment regimens were administered to OSCC patients and the changes in immune function, intestinal bacteria composition and short-chain fatty acids were measured 1 week before and 6 months after therapy. GraphPad Prism 9.0 software package was used for data analysis. RESULTS: Immunological function measurements indicated significantly lower levels of lymphocyte subsets (including CD3⁺, CD4⁺, NK, CD4⁺/CD8⁺) and immunoglobulins (including IgG, IgA, IgM) in the peripheral blood of OSCC patients before treatment compared to healthy volunteers (P<0.05), as well as remarkably lower levels of serum cytokines (including TNF-α、IL-4、IL-6) (P<0.05). Following 6 months of conventional treatment, there was an improvement in immune function in OSCC patients compared to all patients before treatment(P<0.05). Compared to healthy volunteers, the diversity of intestinal bacteria was decreased in OSCC patients before treatment, whereas the diversity of intestinal bacteria recovered in OSCC patients after conventional treatment. At the phylum, the distribution of Epsilonbacteraeota, Proteobacteria and Patescibacteria were significantly elevated and the concentration of Verrucomicrobia was decreased in OSCC patients before treatment compared to healthy volunteers(P<0.05). Intriguingly, convention therapy reversed the disturbance of intestinal bacteria, including downgrading levels of Epsilonbacteraeota, Proteobacteria and Patescibacteria and increasing levels of Verrucomicrobia(P<0.05). Short-chain fatty acids (including acetic acid, propionic acid and butyric acid) were present at a lower level in the intestine of OSCC patients before treatment and were elevated after conventional treatment. CONCLUSIONS: Conventional treatment remarkably enhances immune function, revitalizes the distribution of intestinal microflora, elevates the content of short-chain fatty acids in the intestine of OSCC patients, thereby improving the patients' health.

Key words: Oral squamous cell carcinoma, Immunological function, Intestinal bacteria, Short-chain fatty acids

CLC Number:

R781.4

QIAN Yi, DENG Chao, XU Xiao-bo, CHEN Ye-jun, HU Yun-ping, HONG Li-lin, FENG Da-jun. Clinical analysis of immune function, intestinal flora changes in patients with oral squamous carcinoma before, after treatment[J]. Shanghai Journal of Stomatology, 2022, 31(5): 523-529.

References

[1] Nichols A, Theurer J, Prisman E, et al.Randomized trial of radiotherapy versus transoral robotic surgery for oropharyngeal squamous cell carcinoma: long-term results of the ORATOR trial[J]. J Clin Oncol, 2022, 40(8): 866-875.
[2] Johnson D, Burtness B, Leemans C, et al.Head and neck squamous cell carcinoma[J]. Nat Rev Dis Primers, 2020, 6(1): 92-99.
[3] Hill S, D'andrea A. Predictive potential of head and neck squamous cell carcinoma organoids[J]. Cancer Discov, 2019, 9(7): 828-830.
[4] 陈晓华, 徐茂林. IL-10 多态性对牙周炎患者牙周微生态的影响[J]. 上海口腔医学, 2020, 29(5): 533-538.
[5] Park SY, Hwang BO, Lim M, et al.Oral-gut microbiome axis in gastrointestinal disease and cancer[J]. Cancers (Basel), 2021, 13(9): 2124.
[6] Turnbaugh PJ, Ley RE, Hamady M, et al.The human microbiome project[J]. Nature, 2007, 449(7164): 804-810.
[7] Krautkramer KA, Fan J, Bäckhed F.Gut microbial metabolites as multi-kingdom intermediates[J]. Nat Rev Microbiol, 2021, 19(2): 77-94.
[8] 中华口腔医学会口腔病理学专业委员会. 口腔癌及口咽癌病理诊断规范[J]. 中国口腔颌面外科杂志, 2020, 18(4): 289-296.
[9] Burstein HJ, Lacchetti C, Anderson H, et al.Adjuvant endocrine therapy for women with hormone receptor-positive breast cancer: ASCO Clinical Practice Guideline focused update[J]. J Clin Oncol, 2019, 37(5): 423-438.
[10] Huang Y, Yang B, Li W. Defining the normal core microbiome of conjunctival microbial communities[J]. Clin Microbiol Infect, 2016, 22(7): 643.e7-643.e12.
[11] Grajeda-Iglesias C, Durand S, Daillère R, et al.Oral administration of Akkermansia muciniphila elevates systemic antiaging and anticancer metabolites[J]. Aging (Albany NY), 2021, 13(5): 6375-6405.
[12] Daisley BA, Chanyi RM, Abdur-Rashid K, et al.Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients[J]. Nat Commun, 2020, 11(1): 4822-4833.
[13] Al-Jaber A, Al-Nasser L, El-Metwally A.Epidemiology of oral cancer in Arab countries[J]. Saudi Med J, 2016, 37(3): 249-255.
[14] Tandon P, Dadhich A, Saluja H, et al.The prevalence of squamous cell carcinoma in different sites of oral cavity at our Rural Health Care Centre in Loni, Maharashtra - a retrospective 10-year study[J]. Contemp Oncol (Pozn), 2017, 21(2): 178-183.
[15] Muttagi SS, Chaturvedi P, Gaikwad R, et al.Head and neck squamous cell carcinoma in chronic areca nut chewing Indian women: Case series and review of literature[J]. Indian J Med Paediatr Oncol, 2012, 33(1): 32-35.
[16] Leemans C, Snijders P, Brakenhoff R.The molecular landscape of head and neck cancer[J]. Nat Rev Cancer, 2018, 18(5): 269-282.
[17] 靳能皓, 南欣荣, 闫星泉. BTG1在78 例口腔鳞癌中的表达及临床意义[J]. 上海口腔医学, 2021, 30(2): 140-144.
[18] Zheng D, Deng W, Song W, et al.Biomaterial-mediated modulation of oral microbiota synergizes with PD-1 blockade in mice with oral squamous cell carcinoma[J]. Nat Biomed Eng, 2022, 6(1): 32-43.
[19] Hayes R, Ahn J, Fan X, et al.Association of oral microbiome with risk for incident head and neck squamous cell cancer[J]. JAMA Oncol, 2018, 4(3): 358-365.
[20] Kenison J, Wang Z, Yang K, et al.The aryl hydrocarbon receptor suppresses immunity to oral squamous cell carcinoma through immune checkpoint regulation[J]. Proc Natl Acad Sci USA, 2021, 118(19): e2012692118.
[21] 吴毓聪, 程亚楠, 陈绍山, 等. IL-12 和 Th 亚群细胞在牙周病免疫病理及免疫调节中的作用[J]. 上海口腔医学, 2020, 29(5): 519-523.
[22] Liu D, Zhong M, Zhan D, et al.Roles of the HGF/Met signaling in head and neck squamous cell carcinoma: focus on tumor immunity (Review)[J]. Oncol Rep, 2020, 44(6): 2337-2344.
[23] Garrido-Rodríguez V, Herrero-Fernández I, Castro MJ, et al.Immunological features beyond CD4/CD8 ratio values in older individuals[J]. Aging(Albany NY), 2021, 13(10): 13443-13459.
[24] Kumar S, Metz D, Ellenberg S, et al. Risk factors and incidence of gastric cancer after detection of helicobacter pylori infection: a large cohort study [J]. Gastroenterology, 2020, 158(3): 527-536.e7.
[25] Doorakkers E, Lagergren J, Engstrand L, et al.Helicobacter pylori eradication treatment and the risk of gastric adenocarcinoma in a Western population[J]. Gut, 2018, 67(12): 2092-2096.
[26] Satheeshkumar P, Mohan M.Oral Helicobacter pylori infection and the risk of oral cancer[J]. Oral Oncol, 2013, 49(6): e20-e21.
[27] Meng X, Wang Q, He C, et al.An inverse association of Helicobacter pylori infection with oral squamous cell carcinoma[J]. J Oral Pathol Med, 2016, 45(1): 17-22.
[28] Cani P, Knauf C.A newly identified protein from Akkermansia muciniphila stimulates GLP-1 secretion[J]. Cell Metab, 2021, 33(6): 1073-1075.
[29] Derosa L, Routy B, Thomas AM, et al.Intestinal Akkermansia muciniphila predicts clinical response to PD-1 blockade in patients with advanced non-small-cell lung cancer[J]. Nat Med, 2022, 28(2): 315-324.
[30] Blacher E, Bashiardes S, Shapiro H, et al.Potential roles of gut microbiome and metabolites in modulating ALS in mice[J]. Nature, 2019, 572(7770): 474-480.
[31] Derrien M, Belzer C, De Vos WM.Akkermansia muciniphila and its role in regulating host functions[J]. Microb. Pathog, 2017, 106: 171-181.
[32] Koh A, De Vadder F, Kovatcheva-Datchary P, et al.From dietary fiber to host physiology: short-chain fatty acids as key bacterial metabolites[J]. Cell, 2016, 165(6): 1332-1345.
[33] 薛佳艺, 朱晓燕, 危常磊, 等. 25 例口腔鳞癌患者唾液代谢组学分析[J]. 上海口腔医学, 2021, 30(2): 201-205.
[34] Carley A, Maurya S, Fasano M, et al.Short-chain fatty acids outpace ketone oxidation in the failing heart[J]. Circulation, 2021, 143(18): 1797-1808.
[35] Bachem A, Makhlouf C, Binger K, et al. Microbiota-derived short-chain fatty acids promote the memory potential of antigen-activated CD8 T cells [J]. Immunity, 2019, 51(2): 285-297.e5.
[36] Zheng DW, Li RQ, An JX, et al.Prebiotics-encapsulated probiotic spores regulate gut microbiota and suppress colon cancer[J]. Adv Mater, 2020, 32(45): e2004529.