结直肠癌术后患者化疗前后外周血NKT及NK细胞表达分析
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摘要
目的观察结直肠癌术后患者化疗前后外周血淋巴细胞亚群的变化,评估患者免疫功能状态变化。方法纳入浙江省肿瘤医院2016年1～12月住院的结直肠癌根治术后Ⅱ～Ⅲ期患者74例,健康对照组为25例同期我院就诊的非恶性肿瘤患者,采用流式细胞术分析辅助化疗第1、6、8周期前1 d外周血淋巴细胞亚群比例。结果结直肠癌根治术后患者外周血中CD3+(P=0.1532)、CD3+CD4+(P=0.1107)、CD3+CD8+(P=0.2576)T细胞与健康对照组比较无差异(P>0.05),而CD3+CD56+NKT细胞(P=0.0210)及CD3-CD56+NK细胞(P=0.0045)较健康对照者显著升高(P<0.05)。术后辅助化疗6周期前NK、NKT细胞比例均无显著变化,P>0.05。8周期前NKT细胞比例无显著变化(P>0.05),NK细胞比例仅轻度下降(19.10±4.63 vs 20.31±4.66,P=0.046)。结论结直肠癌根治术后患者NK及NKT细胞比例较健康人显著升高,且辅助化疗后表达率保持稳定。
Objective To observe the changes of peripheral blood lymphocyte subsets in patients with postoperative colorectal cancer before and after chemotherapy, and to evaluate the changes of immune function status. Methods 74 patients with stage Ⅱ-Ⅲ colorectal cancer after radical resection admitted in Zhejiang Cancer Hospital from January to December 2016 were enrolled. 25 non-malignant patients in the same period in our hospital were selected as the control group. Flow cytometry was used to analyze the proportion of peripheral blood lymphocyte subsets at one day before the first, sixth and eighth cycles of adjuvant chemotherapy. Results There were no differences in CD3+(P =0.1532), CD3+CD4+(P=0.1107), CD3+CD8+(P=0.2576) T cells in the peripheral blood between patients with colorectal cancer after radical operation and control group(P>0.05). While CD3+CD56+NKT cells(P=0.0210) and CD3-CD56+NK cells(P=0.0045) in the patients with colorectal cancer after radical operation were significantly higher than those of the control group(P <0.05). There was no significant change in the proportion of NK and NKT cells before 6 cycles of postoperative adjuvant chemotherapy(P>0.05). There was no significant change in the proportion of NKT cells before 8 cycles(P>0.05), and the proportion of NK cells only decreased slightly(19.10±4.63 vs 20.31±4.66,P=0.046). Conclusion The proportion of NK and NKT cells in patients with colorectal cancer after radical resection was significantly higher than that in healthy people, and the expression rate remains stable after adjuvant chemotherapy.
Objective To observe the changes of peripheral blood lymphocyte subsets in patients with postoperative colorectal cancer before and after chemotherapy, and to evaluate the changes of immune function status. Methods 74 patients with stage Ⅱ-Ⅲ colorectal cancer after radical resection admitted in Zhejiang Cancer Hospital from January to December 2016 were enrolled. 25 non-malignant patients in the same period in our hospital were selected as the control group. Flow cytometry was used to analyze the proportion of peripheral blood lymphocyte subsets at one day before the first, sixth and eighth cycles of adjuvant chemotherapy. Results There were no differences in CD3+(P =0.1532), CD3+CD4+(P=0.1107), CD3+CD8+(P=0.2576) T cells in the peripheral blood between patients with colorectal cancer after radical operation and control group(P>0.05). While CD3+CD56+NKT cells(P=0.0210) and CD3-CD56+NK cells(P=0.0045) in the patients with colorectal cancer after radical operation were significantly higher than those of the control group(P <0.05). There was no significant change in the proportion of NK and NKT cells before 6 cycles of postoperative adjuvant chemotherapy(P>0.05). There was no significant change in the proportion of NKT cells before 8 cycles(P>0.05), and the proportion of NK cells only decreased slightly(19.10±4.63 vs 20.31±4.66,P=0.046). Conclusion The proportion of NK and NKT cells in patients with colorectal cancer after radical resection was significantly higher than that in healthy people, and the expression rate remains stable after adjuvant chemotherapy.
引文
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[15]顾园龙,王东亮,张艳桥.NK细胞在肿瘤免疫治疗中的进展[J].国际免疫学杂志,2012,35(3):215-219.
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[19]Emens IrA,Middleton G.The interplay of immunotherapy and chemotherapy:Harnessing potential synergies[J].Cancer Immunol Res,2015,3(5):436-443.
[20]Ottaiano A,Napolitano M,Scala,et al.Natural killer cells activity in a metastatic colorectal cancer patient with complete and long lasting response to therapy[J].World J Clin Cases,2017,5(11):390-396.
[2]Reeves E,James E.Antigen processing and immune regulation in the response to tumours[J].Immunology,2017,150:16-24.
[3]张国庆,赵宏,温新宇.大肠癌患者化疗前后淋巴细胞亚群变化[J].中国医学科学院学报,2013,35(2):155-160.
[4]Hanahan D,Weinberg RA.Hallmarks of cancer:The next generation[J].Cell,2011,144(5):646-674.
[5]Mohme M,Riethdorf S,Pantel K.Circulating and disseminated tumour cells-mechanisms of immune surveillance and escape[J].Nat Rev Clin Oncol,2017,14:155-167.
[6]Wolf BJ,Choi JE,Exley MA.Novel approaches to exploiting invariant nKT Cells in cancer immunotherapy[J].Frontiers in Immunology,e1664-3224,2018,9:384-384.
[7]Rossjohn J,Pellicci DG,Patel O,et al.Recognition of CD1d-restricted antigens by natural killer Tcells[J].Nat Rev Immunol,2012,12(12):845-857.
[8]Shissler SC,Lee MS,Webb TJ.Mixed signals:Co-stimulation in invariant natural killer T cell-mediated cancer immunotherapy[J].Front Immunol,2017,8:1447.
[9]吴劼,苏敏,王文祥.NKT细胞在肿瘤免疫中的作用与机制的研究进展[J].肿瘤药学,2018,8(4):494-497.
[10]Shissler SC,Bollino DR,Tiper IV,et al.Immunotherapeutic strategies targeting natural killer T cell responses in cancer[J].Immunogenetics,2016,68(8):623-638.
[11]Macho-Fernandez E,Brigl M.The extended family of CD1d-restricted NKT cells:Sifting through a mixed bag of TCRs,antigens,and functions[J/OL].Front Immunol,2015,6:360-365.
[12]陈佳文,艾绍正,吴涛,等.NKT细胞对肿瘤免疫调节的研究进展[J].临床肿瘤学杂志,2017,22(12):1135-1138.
[13]McEwen-Smith RM,Salio M,Cerundolo V.The regulatory role of invariant NKT cells in tumor immunity[J].Cancer Immunol Res,2015,3(5):425-435.
[14]Vivier E,Raulet DH,Morettn A,et al.Innate or adaptive immunity The example of natural killer cells[J].Science,2011,331(6013):44-49.
[15]顾园龙,王东亮,张艳桥.NK细胞在肿瘤免疫治疗中的进展[J].国际免疫学杂志,2012,35(3):215-219.
[16]Trotta AM,Ottaiano A,Scala S,et al.Prospective evaluation of cetuximab-mediated antibody-dependent cell cytotoxicity in metastatic colorectal cancer patients predicts treatment efficacy[J].Cancer Immunol Res,2016,4:366-374.
[17]Smyrk TC,Watson P,Lynch HT,et al.Tumor-inltrating lymphocytes are a marker for microsatellite instability in colorectal carcinoma[J].Cancer,2001,91:2417-2422.
[18]Liosa NJ,Cruise M,Housseau F,et al.The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints[J].Cancer Discov,2015,5(1):43-51.
[19]Emens IrA,Middleton G.The interplay of immunotherapy and chemotherapy:Harnessing potential synergies[J].Cancer Immunol Res,2015,3(5):436-443.
[20]Ottaiano A,Napolitano M,Scala,et al.Natural killer cells activity in a metastatic colorectal cancer patient with complete and long lasting response to therapy[J].World J Clin Cases,2017,5(11):390-396.