放疗对食管癌患者免疫功能及预后的影响

doi:10.3760/cma.j.issn.1673422X.2016.12.002

摘要/Abstract

摘要： 目的观察食管癌患者放疗前后免疫功能的动态变化，探讨与其相关的临床预后因素。方法选取2010年1月至2013年12月在南通大学第二附属医院放疗科就诊的食管癌放疗患者90例，分别于放疗前、放疗结束及放疗后3个月使用流式细胞仪检测患者外周血T淋巴细胞亚群及NK细胞比例，以30例本院健康体检者外周血人群为对照观察其变化。分析患者放疗前后免疫功能变化与临床特征及预后的关系。结果食管癌患者放疗前外周血CD4+、CD8+、CD4+/CD8+比值、NK细胞百分比分别为28.23%±8.22%、31.79%±7.61%、0.93±0.34、11.37%±4.57%，与对照组（36.03%±9.71%、27.26%±7.70%、1.34±0.27、15.31%±5.13%）相比，差异均有统计学意义（t=4.292，P=0.000；t=2.811，P=0.006；t=5.894，P=0.000；t=3.965，P=0.000）；放疗前外周血CD3+细胞百分比为58.13%±9.46%，与对照组（60.06%±8.67%）相比，差异无统计学意义（t=0.998，P=0.325）。放疗后3个月免疫指标CD3+（59.27%±9.92%）、CD4+（30.51%±9.04%）、CD8+（29.79%±6.98%）、NK细胞（10.62%±4.43%）逐渐恢复到放疗前水平（t=0.789，P=0.431；t=1.769，P=0.079；t=1.837，P=0.068；t=1.113，P=0.267)。放疗后免疫功能改变（CD4+、CD8+、CD4+/CD8+、NK细胞）与是否存在骨髓抑制（t=4.050，P=0.001；t=2.180，P=0.015；t=2.130，P=0.020；t=3.520，P=0.003）及照射体积大小（t=5.170，P=0.000；t=3.350，P=0.026；t=8.750，P=0.000；t=2.490，P=0.043）有关。生存分析显示：放疗后3个月免疫功能恢复良好的患者其中位生存时间优于恢复不良者（23个月∶17个月，χ2=6.820，P=0.009）。结论食管癌患者放疗前处于免疫功能抑制状态，放疗实施会进一步加重免疫抑制，其加重程度与骨髓抑制及照射体积相关；放疗后3个月患者免疫功能有所恢复，恢复良好者预后较好。

关键词: 食管肿瘤, 放射疗法, T淋巴细胞亚群, 自然杀伤细胞

Abstract: ObjectiveTo observe the dynamic changes of the immune function in patients with esophageal cancer during the radiotherapy and also to explore its association with the clinical prognosis factors. MethodsTotally 90 cases with esophageal cancer received radiotherapy in Second Affiliated Hospital of Nantong University from January 2010 to December 2013 were collected. The proportions of Tlymphocyte subsets and natural killer (NK) cells in the peripheral blood were detected by the flow cytometry from start to finish and 3 months after radiotherapy. Meanwhile, 30 cases of healthy subjects were taken as control. The changes of the immune function in the patients during the radiotherapy and the correlation between the changes and clinicopathologic features were analyzed, as well as the clinical prognostic factors were further evaluated. ResultsThe difference of proportions of CD4+ T cells (28.23%±8.22%), CD8+ T cells (31.79%±7.61%), CD4+/CD8+ ratio (0.93±0.34) and NK cells (11.37%±4.57%) in preradiotherapy patients with esophageal cancer were statistically significant (t=4.292, P=0.000; t=2.811, P=0.006; t=5.894, P=0.000; t=3.965, P=0.000) compared with control group (36.03%±9.71%, 27.26%±7.70%, 1.34±0.27, 15.31%±5.13%); but the proportions of CD3+ T cells (58.13%±9.46%) had no obvious difference (t=0.988, P=0.325) compared with control group (60.06%±8.67%). The immune function of esophageal patients in 3 months after radiotherapy such as CD3+ (59.27%±9.92%), CD4+ (30.51%±9.04%), CD8+ (29.79%±6.98%) and NK cells (10.62%±4.43%) gradually returned to the preradiotherapy levels (t=0.789, P=0.431; t=1.769, P=0.079; t=1.837, P=0.068; t=1.113, P=0.267). The changes of immune function (CD4+, CD8+, CD4+/CD8+ ratio, NK cells) after radiotherapy were related to the bone marrow suppression (t=4.050, P=0.001; t=2.180, P=0.015; t=2.130, P=0.020; t=3.520, P=0.003) and irradiation volumes (t=5.170, P=0.000; t=3.350, P=0.026; t=8.750, P=0.000; t=2.490, P=0.043). Survival analysis showed that the patients whose immune function recovered better in 3 months after radiotherapy had a longer median survival time than those recovered bad (23 months vs. 17 months, χ2=6.820, P=0.009). ConclusionThe patients of esophageal cancer are immunosuppressive before radiotherapy and will further aggravated after radiotherapy. The degree of immunosuppression is associated with bone marrow suppression and irradiation volumes. The immune function of patients are recovered in 3 months after radiotherapy, and the patients whose immune function recovered better have good prognosis.

Key words: Esophageal neoplasms, Radiotherapy, Tlymphocyte subsets, Natural killer cells

王小博, 吴迪军, 陈卫平, 刘健. 放疗对食管癌患者免疫功能及预后的影响[J]. 国际肿瘤学杂志, 2016, 43(12): 886-891.

WANG Xiao-Bo, WU Di-Jun, CHEN Wei-Ping, LIU Jian. Influence of radiotherapy on the immune function and prognosis of patients with esophageal cancer[J]. Journal of International Oncology, 2016, 43(12): 886-891.

参考文献

1］ Liu JY, Li F, Wang LP, et al. CTLvs Treg lymphocyteattracting chemokines, CCL4 and CCL20, are strong reciprocal predictive markers for survival of patients with oesophageal squamous cell carcinoma［J］. Br J Cancer, 2015, 113(5): 747755. DOI: 10.1038/bjc.2015.290. ［2］ Wang G, Sun Y, Ji C, et al. Correlation between the CD4+CD25 high regulatory T cells and the outcome of chemotherapy in advanced esophageal carcinoma［J］. Hepatogastroenterology, 2013, 60(124): 704708. DOI: 10.5754/hge12953. ［3］王俞, 崔书中. 恶性肿瘤患者的免疫功能状态及免疫治疗研究进展［J］. 中国肿瘤临床, 2014, 41(13): 876879. DOI: 10.3969/j.issn.10008179.20131206. ［4］ Nabeki B, Ishigami S, Uchikado Y, et al. Interleukin32 expression and Treg infiltration in esophageal squamous cell carcinoma［J］. Anticancer Res, 2015, 35(5): 29412947. ［5］陈传生, 游涛, 林纲, 等. 同步放化疗对食管癌患者T淋巴细胞亚群及自然杀伤细胞的影响［J］. 海南医学院学报, 2014, 20(12): 17111713. DOI: 10.13210/j.cnki.jhmu.20141011.002. ［6］陈超, 李华峰. 放疗前后食管癌患者红细胞免疫功能和T淋巴细胞亚群的变化［J］. 浙江医学, 2015, 37(3): 229231. ［7］ Tsuchikawa T, Md MM, Yamamura Y, et al. The immunological impact of neoadjuvant chemotherapy on the tumor microenvironment of esophageal squamous cell carcinoma［J］. Ann Surg Oncol, 2012, 19(5): 17131719. DOI: 10.1245/s104340111906x. ［8］ Reginato E, Lindenmann J, Langner C, et al. Photodynamic therapy downregulates the function of regulatory T cells in patients with esophageal squamous cell carcinoma［J］. Photochem Photobiol Sci, 2014, 13(9): 12811289. DOI: 10.1039/c4pp00186a. ［9］ Narita M, Kanda T, Abe T, et al. Immune responses in patients with esophageal cancer treated with SART1 peptidepulsed dendritic cell vaccine［J］. Int J Oncol, 2015, 46(4): 16991709. DOI: 10.3892/ijo.2015.2846. ［10］王胜根, 杨朝群. 放疗中不同等效方野对T淋巴细胞亚群和IL2的影响［J］. 农垦医学, 2007, 29(2): 105107. DOI: 10.3969/j.issn.10081127.2007.02.010. ［11］王忠明, 刘桂荣, 黄关宏, 等. 食管癌放疗患者T淋巴细胞和自然杀伤细胞水平的临床研究［J］. 肿瘤研究与临床, 2011, 23(10): 674677. DOI: 10.3760/cma.j.issn.10069801.2011.10.008.

[1]	杨蜜, 别俊, 张加勇, 邓佳秀, 唐组阁, 卢俊. 局部晚期可切除食管癌新辅助治疗疗效及预后分析[J]. 国际肿瘤学杂志, 2024, 51(6): 332-337.
[2]	高凡, 王萍, 杜超, 褚衍六. 肠道菌群与结直肠癌非手术治疗的相关研究进展[J]. 国际肿瘤学杂志, 2024, 51(6): 376-381.
[3]	刘静, 刘芹, 黄梅. 基于SMOTE算法的食管癌放化疗患者肺部感染的预后模型构建[J]. 国际肿瘤学杂志, 2024, 51(5): 267-273.
[4]	万芳, 杨钢, 李睿, 万启晶. 食管癌患者血清miR-497、miR-383水平及临床意义[J]. 国际肿瘤学杂志, 2024, 51(4): 204-209.
[5]	李书月, 马辰莺, 周菊英, 徐晓婷, 秦颂兵. 寡转移非小细胞肺癌的放疗进展[J]. 国际肿瘤学杂志, 2024, 51(3): 170-174.
[6]	李济时, 陆钊群, 刘俊茹, 吕建勋, 陈霜, 沈琳, 徐志渊, 吴平安. 新辅助放疗联合部分喉切除术治疗喉滑膜肉瘤1例并文献复习[J]. 国际肿瘤学杂志, 2024, 51(2): 123-125.
[7]	中国医师协会放射肿瘤治疗医师分会, 中华医学会放射肿瘤治疗学分会, 中国抗癌协会肿瘤放射治疗专业委员会. 中国食管癌放射治疗指南（2023年版）[J]. 国际肿瘤学杂志, 2024, 51(1): 1-20.
[8]	高新雨, 李振江, 孙洪福, 韩丹, 赵倩, 刘成新, 黄伟. 基于MR加速器的MR引导放疗在食管癌患者中的临床应用[J]. 国际肿瘤学杂志, 2024, 51(1): 37-42.
[9]	崔腾璐, 吕璐, 孙鹏飞. 放疗联合免疫治疗在头颈部鳞状细胞癌治疗中的应用[J]. 国际肿瘤学杂志, 2023, 50(9): 548-552.
[10]	山东省医学会肺癌食管癌多学科联合委员会. 山东省医学会食管癌多学科规范化诊疗指南（2023年版）[J]. 国际肿瘤学杂志, 2023, 50(7): 385-397.
[11]	李青珊, 谢鑫, 张楠, 刘帅. 放疗联合系统治疗在乳腺癌中的应用进展[J]. 国际肿瘤学杂志, 2023, 50(6): 362-367.
[12]	邢明泉, 葛洪峰, 张丽侠, 韩浩, 吴维霞. 疑似免疫性血小板减少症的侵袭性自然杀伤细胞白血病1例[J]. 国际肿瘤学杂志, 2023, 50(5): 318-320.
[13]	许萌, 姜伟, 朱海涛, 曹雄锋. 癌相关成纤维细胞在肿瘤放疗抵抗中的研究进展[J]. 国际肿瘤学杂志, 2023, 50(4): 227-230.
[14]	石小琪, 汪红艳. 肠道菌群与放射性肠炎的相互作用及研究进展[J]. 国际肿瘤学杂志, 2023, 50(4): 244-247.
[15]	冀世玉, 张明鑫, 谢华红, 白渊, 王彤. 不同支架治疗晚期食管癌患者的疗效观察[J]. 国际肿瘤学杂志, 2023, 50(2): 76-81.