放射治疗对肺癌患者IL-18、sMICA及NK细胞的影响
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摘要
为探讨肺癌患者放射治疗(简称放疗)前及放疗不同阶段NK细胞存活率及IL-18、可溶性MHC-Ⅰ类链相关蛋白A(soluble MHC classⅠ-related chain A, sMICA)浓度变化,对肿瘤科收治的30例肺癌放疗患者,通过ELISA检测IL-18、sMICA浓度,应用磁珠分选检测NK细胞存活率。结果显示,sMICA浓度在放疗前最低,而在放疗后,随着放疗剂量的增加逐渐降低(P<0.05);IL-18浓度随着放疗剂量的增加并无明显变化,且与放疗前无显著差异(P> 0.05);NK细胞活性在放疗后与放疗前无显著差异,且不随剂量增加而明显变化(P> 0.05)。由此,放疗对肺癌患者外周血中NK细胞的存活率和IL-18浓度无明显影响;放疗可降低患者外周血中肿瘤抗原sMICA浓度,表明肿瘤免疫逃逸功能被抑制,放疗可间接增强机体的免疫功能。
In order to investigate the survival rate of NK cells and the changes of IL-18 and soluble MHC class Ⅰ-related chain A(sMICA) concentrations in different stages of radiation therapy(referred to as radiotherapy) for lung cancer patients, we detected IL-18 and sMICA by ELISA and NK cell survival rate by magnetic bead sorting in 30 patients with lung cancer treated by radiotherapy in the Oncology Department. The results showed that the concentration of sMICA before radiotherapy was generally lower than post-radiotherapy, while among the different dosage groups, the concentration of sMICA decreased gradually with the increase of radiation dose(P < 0.05)(2 000, 4 000, 6 000 cGy), while the concentration of IL-18 did not change significantly with the increase of radiotherapy dosage(P > 0.05). NK cell activity did not change significantly with the increase of radiotherapy dosage(P > 0.05). In conclusion, radiation has no significant effect on the survival rate of NK cells in the peripheral blood of lung cancer patients and does not affect the killing effect of NK cells on tumor cells. Radiotherapy can reduce the sMICA concentration in patients' peripheral blood, indicating that the tumor escape is inhibited and thus indirectly enhances the body's immune function.
In order to investigate the survival rate of NK cells and the changes of IL-18 and soluble MHC class Ⅰ-related chain A(sMICA) concentrations in different stages of radiation therapy(referred to as radiotherapy) for lung cancer patients, we detected IL-18 and sMICA by ELISA and NK cell survival rate by magnetic bead sorting in 30 patients with lung cancer treated by radiotherapy in the Oncology Department. The results showed that the concentration of sMICA before radiotherapy was generally lower than post-radiotherapy, while among the different dosage groups, the concentration of sMICA decreased gradually with the increase of radiation dose(P < 0.05)(2 000, 4 000, 6 000 cGy), while the concentration of IL-18 did not change significantly with the increase of radiotherapy dosage(P > 0.05). NK cell activity did not change significantly with the increase of radiotherapy dosage(P > 0.05). In conclusion, radiation has no significant effect on the survival rate of NK cells in the peripheral blood of lung cancer patients and does not affect the killing effect of NK cells on tumor cells. Radiotherapy can reduce the sMICA concentration in patients' peripheral blood, indicating that the tumor escape is inhibited and thus indirectly enhances the body's immune function.
引文
[1] 丁军颖,王润田.人MICA基因多态性和表达特性与肿瘤的关系[J].现代免疫学,2007,27(2):165-168.
[2] Liu Y,Guo X,Xing M,et al.Prognostic value of serum levels of soluble MICA (sMICA) in patients with prostate cancer[J].Br J Biomed Sci,2018,75(2):98-100.
[3] 王云炎,徐宗源,孟峻嵩,等.MICA基因与肿瘤[J].国际肿瘤学杂志,2013,40(4):243-246.
[4] Herrera FG,Bourhis J,Coukos G.Radiotherapy combination opportunities leveraging immunity for the next oncology practice[J].CA Cancer J Clin,2017,67(1):65-85.
[5] Muroyama Y,Nirschl TR,Kochel CM,et al.Stereotactic radiotherapy increases functionally suppressive regulatory T cells in the tumor microenvironment[J].Cancer Immunol Res,2017,5(11):992-1004.
[6] Okamura H,Tsutsi H,Komatsu T,et al.Cloning of a new cytokine that indues IFN-gamma production by T cell[J].Nature,1995,387(6552):88-91.
[7] Avanzi MP,Yeku O,Li XH,et al.Engineered tumor-targeted T cells mediate enhanced anti-tumor efficacy both directly and through activation of the endogenous immune system[J].Cell Rep,2018,23(7):2130-2141.
[8] Esmailbeig M,Ghaderi A.Interleukin-18:A regulator of cancer and autoimmune diseases[J].Eur Cytokine Netw,2017,28(4):127-140.
[9] Tse BW,Russell PJ,Lochner M,et al.IL-18 inhibits growth of murine orthotopic prostate carcinomas via both adaptive and innate immune mechanisms[L].PLoS One,2011,6(9):e24241.
[10] Yamanishi K,Mukai K,Hashimoto T,et al.Physiological and molecular effects of interleukin-18 administration on the mouse kidney[J].J Transl Med,2018,16(1):51.
[11] 徐玢,马小彤,董成亚,等.小鼠IL-18基因修饰瘤苗的抗白血病作用研究[J].现代免疫学,2007,27(4):274-278.
[12] 郭兴军.白介素18对胰腺癌免疫治疗作用及其机制的研究[D].武汉:华中科技大学,2015.
[13] 王晓梦,李玲,于津浦,等.四种NK细胞体外扩增方案的比较[J].中国肿瘤生物治疗杂志,2013,20(3):336-341.
[14] Senju H,Kumagai A,Nakamura Y,et al.Effect of IL-18 on the expansion and phenotype of human natural killer cells:Application to cancer immunotherapy[J].Int J Biol Sci,2018,14(3):331-340.
[2] Liu Y,Guo X,Xing M,et al.Prognostic value of serum levels of soluble MICA (sMICA) in patients with prostate cancer[J].Br J Biomed Sci,2018,75(2):98-100.
[3] 王云炎,徐宗源,孟峻嵩,等.MICA基因与肿瘤[J].国际肿瘤学杂志,2013,40(4):243-246.
[4] Herrera FG,Bourhis J,Coukos G.Radiotherapy combination opportunities leveraging immunity for the next oncology practice[J].CA Cancer J Clin,2017,67(1):65-85.
[5] Muroyama Y,Nirschl TR,Kochel CM,et al.Stereotactic radiotherapy increases functionally suppressive regulatory T cells in the tumor microenvironment[J].Cancer Immunol Res,2017,5(11):992-1004.
[6] Okamura H,Tsutsi H,Komatsu T,et al.Cloning of a new cytokine that indues IFN-gamma production by T cell[J].Nature,1995,387(6552):88-91.
[7] Avanzi MP,Yeku O,Li XH,et al.Engineered tumor-targeted T cells mediate enhanced anti-tumor efficacy both directly and through activation of the endogenous immune system[J].Cell Rep,2018,23(7):2130-2141.
[8] Esmailbeig M,Ghaderi A.Interleukin-18:A regulator of cancer and autoimmune diseases[J].Eur Cytokine Netw,2017,28(4):127-140.
[9] Tse BW,Russell PJ,Lochner M,et al.IL-18 inhibits growth of murine orthotopic prostate carcinomas via both adaptive and innate immune mechanisms[L].PLoS One,2011,6(9):e24241.
[10] Yamanishi K,Mukai K,Hashimoto T,et al.Physiological and molecular effects of interleukin-18 administration on the mouse kidney[J].J Transl Med,2018,16(1):51.
[11] 徐玢,马小彤,董成亚,等.小鼠IL-18基因修饰瘤苗的抗白血病作用研究[J].现代免疫学,2007,27(4):274-278.
[12] 郭兴军.白介素18对胰腺癌免疫治疗作用及其机制的研究[D].武汉:华中科技大学,2015.
[13] 王晓梦,李玲,于津浦,等.四种NK细胞体外扩增方案的比较[J].中国肿瘤生物治疗杂志,2013,20(3):336-341.
[14] Senju H,Kumagai A,Nakamura Y,et al.Effect of IL-18 on the expansion and phenotype of human natural killer cells:Application to cancer immunotherapy[J].Int J Biol Sci,2018,14(3):331-340.