口腔鳞状细胞癌患者治疗前后外周血免疫细胞的检测及其临床意义的研究
发布时间：2018-07-29 20:22
【摘要】：背景与目的:口腔鳞状细胞癌是口腔颌面部最常见的恶性肿瘤,好发于舌、牙龈、唇、颊、颌骨等部位。目前,该疾病的治疗方法仍以手术为主,并辅以局部放疗、全身化疗等综合治疗,患者虽在组织保存和整体生活质量方面有所受益,但却由于创伤大、高复发率、高转移率等而导致预后欠佳。因此,越来越多的学者致力于口腔颌面部鳞状细胞癌的病因研究,以期从病因入手,寻求更有效的治疗办法。随着免疫学和分子生物学的进展,免疫因素逐渐引起关注。本研究旨在运用流式细胞术,通过对口腔鳞状细胞癌患者手术及化疗前后外周血免疫细胞表达水平的研究,探讨机体自身免疫功能状态的不同,从免疫学角度对口腔鳞状细胞癌的发病机制做进一步研究,有助于优化免疫治疗方案和增强抗肿瘤免疫应答的靶向治疗效果,为口腔鳞状细胞癌的免疫治疗提供可靠的理论依据。资料与方法:1.临床资料:选择郑州大学第一附属医院口腔颌面外科2015年2月至2016年8月经术后病理检查确诊为口腔鳞状细胞癌的患者40例,全部病例均有明确的病理诊断及完整的临床资料。其中男性22例,女性18例;年龄29~81岁。患者入院前未进行过任何抗肿瘤治疗;排除全身淋巴系统来源性疾病;发病部位包括舌、颊、牙龈、口底等部位。另选取15例健康查体者作为健康对照组。2.方法:化疗药物选用氟尿嘧啶注射液,连用5天;奥沙利铂注射液,第1天。治疗组病人分别于手术前2天、手术后3周即术后第一周期化疗前2天、第一周期化疗后2周即第二周期化疗前2天、第二周期化疗后2周采集新鲜外周血。健康对照组常规采集新鲜外周血。采集的血液样本经流式细胞术检测其中的T淋巴细胞亚群CD3+、CD4~+、CD8+的百分率及CD4~+/CD8+的比值;B淋巴细胞(CD19+)百分率;NK细胞(CD56+)百分率。结果:1.手术前口腔鳞状细胞癌患者外周血CD3+、CD4~+、CD8+、NK及B细胞的所占比例与健康对照组人群比较,手术前患者CD3+、CD4~+和B细胞的表达降低,CD8+和NK细胞的表达增加,CD4~+/CD8+比值下降或倒置,差别均有统计学意义(P㩳0.05)。2.手术3周后检测口腔鳞状细胞癌患者外周血免疫细胞,CD3+的表达仍明显低于健康对照组,与术前数据比较虽然显示有小范围的提高,但经统计计算二者间差别无统计学意义(P㧐0.05)。CD4~+的表达也低于健康对照组(P㩳0.05),但与术前比较,有较大幅度的升高(P㩳0.05)。CD8+的表达明显低于术前状态(P㩳0.05),且与健康对照组相比差别有统计学意义(P㩳0.05)。NK细胞的表达与健康对照组比较差别无显著性(P㧐0.05),但手术前后NK细胞的表达却有着明显的变化(P㩳0.05),表现为手术后口腔鳞状细胞癌患者外周血中NK细胞的表达较手术前有所下降。术后B细胞的表达显著低于健康对照组的表达水平(P㩳0.05),与术前相比虽略有升高,但差别无统计学意义(P0.05)。CD4~+/CD8+的比值尽管仍未恢复至健康对照组水平(P㩳0.05),但其值和术前相比也有了一定程度的回升(P㩳0.05)。3.术后3周检测结果即为第一周期化疗前2天检测指标。经一个周期化疗结束后2周前来复诊,抽取外周血检测各免疫细胞表达情况,即为第一周期化疗后检测结果。第一周期化疗后口腔鳞状细胞癌患者外周血中CD3+的表达仍低于健康对照组且较化疗前相比变化不大(P㧐0.05)。CD4~+的表达与化疗前相比无显著性差别(P㧐0.05),同样低于健康对照组(P㩳0.05)。CD8+的表达与化疗前相比有着显著的差别(P㩳0.05),主要表现为化疗后口腔鳞状细胞癌患者外周血中CD8+的表达较化疗前大幅度下降,且与健康对照组比较差别无显著性(P㧐0.05)。NK细胞的表达与化疗前相比变化不大(P㧐0.05),但仍略高于健康对照组(P㧐0.05)。B细胞在低于健康对照组(P㩳0.05)的情况下与化疗前相比有了一定的改善(P㧐0.05)。CD4~+/CD8+的比值尽管仍未恢复至健康对照组水平(P㩳0.05),但较化疗前有所升高(P㧐0.05)。4.第一周期化疗后2周复诊检测结果即为第二周期化疗前2天检测指标。再经第二个周期化疗结束后2周前来复诊,抽取外周血检测各免疫细胞表达情况,即为第二周期化疗后检测结果。第二周期化疗后口腔鳞状细胞癌患者外周血中CD3+的表达较化疗前有小幅度的升高,低于健康对照组(P㧐0.05)。CD4~+和B细胞与化疗前相比表达水平明显增高(P㩳0.05),稍低于健康对照组水平(P0.05)。CD8+和NK细胞化疗后较化疗前表达均有所下降(P0.05),但尚未降至健康对照组水平(P0.05)。CD4~+/CD8+的比值较化疗前有了一定程度的回升(P㩳0.05),接近健康对照组水平(P0.05)。结论:1.口腔鳞状细胞癌患者较正常人存在着免疫抑制现象。2.手术后及经奥沙利铂加氟尿嘧啶的两周期化疗后,口腔鳞状细胞癌患者的免疫功能仍处于低下状态。手术及化疗时的营养支持治疗对患者的免疫状态可起到一定的改善作用,解除机体内部分免疫功能受到抑制的现象,有利于肿瘤患者的治疗。3.外周血中免疫细胞的表达水平可以作为口腔癌患者治疗过程中评估机体免疫状态的临床监测指标。
[Abstract]:Background and objective: oral squamous cell carcinoma is the most common malignant tumor in the oral and maxillofacial region. It is well distributed in the tongue, gingival, lip, cheek and jaw. At present, the treatment of this disease is still based on surgery, combined with local radiotherapy, systemic chemotherapy and other comprehensive treatment, although the patient has benefited from the preservation of the tissue and the quality of the whole life. Therefore, more and more scholars are devoted to the study of the etiology of oral and maxillofacial squamous cell carcinoma in order to seek more effective treatment from the cause of the disease. With the progress of immunology and molecular biology, the immune factors gradually attract attention. This study aims to use flow. Through the study of the expression level of immune cells in peripheral blood of patients with oral squamous cell carcinoma before and after chemotherapy and before and after chemotherapy, a further study on the pathogenesis of oral squamous cell carcinoma is further studied from the immunological point of view, which helps to optimize the immunotherapy scheme and enhance the immune response to the tumor. The effect of targeted therapy provides a reliable theoretical basis for the immunotherapy of oral squamous cell carcinoma. Data and methods: 1. clinical data: 40 cases of oral squamous cell carcinoma were diagnosed in oral and maxillofacial surgery of the First Affiliated Hospital of Zhengzhou University from February 2015 to 8 menstruation after 8 menstruation, and all cases had clear pathology. Diagnosis and complete clinical data, of which 22 men, 18 women, age 29~81 years old. The patients were not treated with any antitumor treatment before admission; the systemic lymphoid diseases were excluded; the sites included the tongue, cheeks, gums, and the bottom of the mouth. 15 healthy subjects were selected as the healthy control group.2. method: the chemotherapeutic drug fluoruria was selected. Injection of pyrimidine for 5 days; Oxaliplatin Injection, first days. The patients in the treatment group were 2 days before the operation, 3 weeks after the operation, 2 days before the first cycle of chemotherapy, 2 days before the first cycle of chemotherapy, 2 days before the second cycle of chemotherapy, and 2 weeks after the second cycle of chemotherapy. The healthy control group collected the blood from the fresh peripheral blood. The percentage of CD3+, CD4~+, CD8+, and CD4~+/CD8+, the percentage of B lymphocyte (CD19+), and the percentage of NK cells (CD56+) were measured by flow cytometry, and the percentage of NK cells (CD56+) in the peripheral blood of 1. patients with oral squamous cell carcinoma before operation was compared with those of the healthy control group compared with those of the healthy control group. The expression of CD3+, CD4~+ and B cells decreased, the expression of CD8+ and NK cells increased, the CD4~+/CD8+ ratio decreased or inverted, the difference was statistically significant (P? 0.05).2. operation 3 weeks after the detection of the peripheral blood immune cells in patients with oral squamous cell carcinoma. The expression of CD3+ was still significantly lower than that in the healthy control group. There was no statistically significant difference between the two groups (P? 0.05).CD4~+ was also lower than the healthy control group (P? 0.05), but compared with pre operation, the expression of.CD8+ was significantly lower than that before the operation (P? 0.05), and compared with the healthy control group, the difference was statistically significant (P? 0.05).NK cells. There was no significant difference between the control group and the healthy control group (P? 0.05), but the expression of NK cells before and after operation was obviously changed (P? 0.05). The expression of NK cells in the peripheral blood of the patients with oral squamous cell carcinoma after operation was lower than that before operation. The expression of B cells after operation was significantly lower than that of the healthy control group (P? 0.05), and the operation of the cells was significantly lower than that of the healthy control group. Although the former was slightly higher, the difference was not statistically significant (P0.05), although the ratio of.CD4~+/CD8+ was still not restored to the level of the healthy control group (P? 0.05), but the value of the difference was also increased to a certain extent compared to the preoperative (P? 0.05).3. after the 3 week of the first cycle chemotherapy, which was 2 weeks before the end of one cycle chemotherapy. After the first cycle chemotherapy, the expression of CD3+ in the peripheral blood of the patients with oral squamous cell carcinoma after the first cycle was still lower than that in the healthy control group and compared with that before the chemotherapy (P? 0.05).CD4~+ expression was not significantly different from that before chemotherapy (P? 0.05). Compared with the healthy control group (P? 0.05), the expression of.CD8+ was significantly different from that before chemotherapy (P? 0.05). The expression of CD8+ in the peripheral blood of patients with oral squamous cell carcinoma after chemotherapy was significantly lower than that before chemotherapy, and there was no significant difference between the healthy control group and the healthy control group (P? 0.05).NK cells. Big (P? 0.05), but still slightly higher than the healthy control group (P? 0.05).B cells in lower than the healthy control group (P? 0.05), compared with pre chemotherapy (P? 0.05).CD4~+/CD8+ ratio although still not recovered to the level of health control group (P? 0.05), but higher than before chemotherapy (P? 0.05).4. first cycle after the first period of chemotherapy after 2 review detection knot The results were 2 days before second cycles of chemotherapy. After second cycles of chemotherapy, the results were taken 2 weeks after the end of chemotherapy, and the expression of the immune cells was detected in the peripheral blood, that is, after the second cycles of chemotherapy. The expression of CD3+ in the peripheral blood of the patients with oral squamous cell carcinoma after second cycles of chemotherapy was slightly higher than that before the chemotherapy. The expression level of.CD4~+ and B cells in the healthy control group (P? 0.05) was significantly higher than that before chemotherapy (P? 0.05). The ratio of.CD8+ and NK cells in the healthy control group (P0.05) was lower than that before chemotherapy (P0.05), but the ratio of the level (P0.05).CD4~+/CD8+ of the healthy control group had not been reduced to a certain extent before the chemotherapy. P? 0.05), close to the level of health control group (P0.05). Conclusion: 1. oral squamous cell carcinoma patients have immune suppression after.2. surgery and after two cycles of oxaliplatin plus fluorouracil, the immune function of patients with oral squamous cell carcinoma is still low. The immune state can be improved and the immune function of the body is suppressed. The expression level of the immune cells in the peripheral blood of.3. can be used as a clinical monitoring index to evaluate the immune state of the oral cancer patients during the treatment process.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R739.8
本文编号：2153899
[Abstract]:Background and objective: oral squamous cell carcinoma is the most common malignant tumor in the oral and maxillofacial region. It is well distributed in the tongue, gingival, lip, cheek and jaw. At present, the treatment of this disease is still based on surgery, combined with local radiotherapy, systemic chemotherapy and other comprehensive treatment, although the patient has benefited from the preservation of the tissue and the quality of the whole life. Therefore, more and more scholars are devoted to the study of the etiology of oral and maxillofacial squamous cell carcinoma in order to seek more effective treatment from the cause of the disease. With the progress of immunology and molecular biology, the immune factors gradually attract attention. This study aims to use flow. Through the study of the expression level of immune cells in peripheral blood of patients with oral squamous cell carcinoma before and after chemotherapy and before and after chemotherapy, a further study on the pathogenesis of oral squamous cell carcinoma is further studied from the immunological point of view, which helps to optimize the immunotherapy scheme and enhance the immune response to the tumor. The effect of targeted therapy provides a reliable theoretical basis for the immunotherapy of oral squamous cell carcinoma. Data and methods: 1. clinical data: 40 cases of oral squamous cell carcinoma were diagnosed in oral and maxillofacial surgery of the First Affiliated Hospital of Zhengzhou University from February 2015 to 8 menstruation after 8 menstruation, and all cases had clear pathology. Diagnosis and complete clinical data, of which 22 men, 18 women, age 29~81 years old. The patients were not treated with any antitumor treatment before admission; the systemic lymphoid diseases were excluded; the sites included the tongue, cheeks, gums, and the bottom of the mouth. 15 healthy subjects were selected as the healthy control group.2. method: the chemotherapeutic drug fluoruria was selected. Injection of pyrimidine for 5 days; Oxaliplatin Injection, first days. The patients in the treatment group were 2 days before the operation, 3 weeks after the operation, 2 days before the first cycle of chemotherapy, 2 days before the first cycle of chemotherapy, 2 days before the second cycle of chemotherapy, and 2 weeks after the second cycle of chemotherapy. The healthy control group collected the blood from the fresh peripheral blood. The percentage of CD3+, CD4~+, CD8+, and CD4~+/CD8+, the percentage of B lymphocyte (CD19+), and the percentage of NK cells (CD56+) were measured by flow cytometry, and the percentage of NK cells (CD56+) in the peripheral blood of 1. patients with oral squamous cell carcinoma before operation was compared with those of the healthy control group compared with those of the healthy control group. The expression of CD3+, CD4~+ and B cells decreased, the expression of CD8+ and NK cells increased, the CD4~+/CD8+ ratio decreased or inverted, the difference was statistically significant (P? 0.05).2. operation 3 weeks after the detection of the peripheral blood immune cells in patients with oral squamous cell carcinoma. The expression of CD3+ was still significantly lower than that in the healthy control group. There was no statistically significant difference between the two groups (P? 0.05).CD4~+ was also lower than the healthy control group (P? 0.05), but compared with pre operation, the expression of.CD8+ was significantly lower than that before the operation (P? 0.05), and compared with the healthy control group, the difference was statistically significant (P? 0.05).NK cells. There was no significant difference between the control group and the healthy control group (P? 0.05), but the expression of NK cells before and after operation was obviously changed (P? 0.05). The expression of NK cells in the peripheral blood of the patients with oral squamous cell carcinoma after operation was lower than that before operation. The expression of B cells after operation was significantly lower than that of the healthy control group (P? 0.05), and the operation of the cells was significantly lower than that of the healthy control group. Although the former was slightly higher, the difference was not statistically significant (P0.05), although the ratio of.CD4~+/CD8+ was still not restored to the level of the healthy control group (P? 0.05), but the value of the difference was also increased to a certain extent compared to the preoperative (P? 0.05).3. after the 3 week of the first cycle chemotherapy, which was 2 weeks before the end of one cycle chemotherapy. After the first cycle chemotherapy, the expression of CD3+ in the peripheral blood of the patients with oral squamous cell carcinoma after the first cycle was still lower than that in the healthy control group and compared with that before the chemotherapy (P? 0.05).CD4~+ expression was not significantly different from that before chemotherapy (P? 0.05). Compared with the healthy control group (P? 0.05), the expression of.CD8+ was significantly different from that before chemotherapy (P? 0.05). The expression of CD8+ in the peripheral blood of patients with oral squamous cell carcinoma after chemotherapy was significantly lower than that before chemotherapy, and there was no significant difference between the healthy control group and the healthy control group (P? 0.05).NK cells. Big (P? 0.05), but still slightly higher than the healthy control group (P? 0.05).B cells in lower than the healthy control group (P? 0.05), compared with pre chemotherapy (P? 0.05).CD4~+/CD8+ ratio although still not recovered to the level of health control group (P? 0.05), but higher than before chemotherapy (P? 0.05).4. first cycle after the first period of chemotherapy after 2 review detection knot The results were 2 days before second cycles of chemotherapy. After second cycles of chemotherapy, the results were taken 2 weeks after the end of chemotherapy, and the expression of the immune cells was detected in the peripheral blood, that is, after the second cycles of chemotherapy. The expression of CD3+ in the peripheral blood of the patients with oral squamous cell carcinoma after second cycles of chemotherapy was slightly higher than that before the chemotherapy. The expression level of.CD4~+ and B cells in the healthy control group (P? 0.05) was significantly higher than that before chemotherapy (P? 0.05). The ratio of.CD8+ and NK cells in the healthy control group (P0.05) was lower than that before chemotherapy (P0.05), but the ratio of the level (P0.05).CD4~+/CD8+ of the healthy control group had not been reduced to a certain extent before the chemotherapy. P? 0.05), close to the level of health control group (P0.05). Conclusion: 1. oral squamous cell carcinoma patients have immune suppression after.2. surgery and after two cycles of oxaliplatin plus fluorouracil, the immune function of patients with oral squamous cell carcinoma is still low. The immune state can be improved and the immune function of the body is suppressed. The expression level of the immune cells in the peripheral blood of.3. can be used as a clinical monitoring index to evaluate the immune state of the oral cancer patients during the treatment process.
【学位授予单位】：郑州大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R739.8
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