化疗对非小细胞肺癌患者外周血NK细胞受体表达的影响及其临床意义

Effect of chemotherapy on the expression of NK cell receptor in peripheral blood of patients with non-small cell lung cancer and its clinical significance

目的探讨非小细胞肺癌患者外周血自然杀伤(natural killer,NK)细胞活化性受体及抑制性受体在化疗前后的变化及其临床意义。方法选取非小细胞肺癌患者50例(Ⅰ~ⅢA期、ⅢB~Ⅳ期各25例)及健康体检者(对照组)10例。用流式细胞仪检测外周血NK细胞活化性受体NKG2D、NCR类(NKp30、NKp44、NKp46)及抑制性受体CD158a、CD158b、CD158e,ⅢB~Ⅳ期化疗2个周期后受体表达。按CD56表达强度对CD56^dim及CD56 bright分别统计。结果非小细胞肺癌ⅢB~Ⅳ期患者CD56^dim活化性受体NKG2D、NKp30低于健康体检者和Ⅰ~ⅢA期患者,非小细胞肺癌Ⅰ~ⅢA期和ⅢB~Ⅳ期CD56^dim活化性受体NKp44表达低于健康体检者(P<0.05)。3组CD56^dim活化性受体NKp46差异均无统计学意义(P>0.05)。3组CD56 bright活化性受体NKG2D、NKp30、NKp44、NKp46差异无统计学意义(P>0.05)。3组CD56^dim抑制性受体CD158a、CD158b、CD158e及CD56 bright抑制性受体CD158a、CD158b、CD158e差异均无统计学意义(P>0.05)。因入组人员缺失,ⅢB~Ⅳ期化疗2个周期后患者入组14例。化疗后非小细胞肺癌ⅢB~Ⅳ期患者CD56^dim活化性受体NKp30、NKp44表达均高于化疗前(P<0.05)。化疗后CD56^dim活化性受体NKp46、NKG2D及抑制性受体CD158a、CD158b、CD158e与化疗前差异均无统计学意义(P>0.05);化疗后CD56 bright活化性受体NKp30、NKp44、NKp46、NKG2D及抑制性受体CD158a、CD158b、CD158e与化疗前差异均无统计学意义(P>0.05)。化疗2个周期后14例患者PR率达78.5%(11/14)。结论ⅢB~Ⅳ期CD56^dim NK细胞活化性受体表达降低,可能与肿瘤微环境导致NK细胞活化性受体细胞毒性作用降低有关;化疗后可以提高NK细胞活化性受体NKp30、NKp44表达,推测化疗可通过提高机体NK细胞活性而发挥其对肿瘤的杀伤作用。

Objective To investigate the changes and clinical significance of natural killer(NK)cell activating receptors and inhibitory receptors in patients with non-small cell lung cancer before and after chemotherapy.Methods Fifty patients with non-small cell lung cancer(25 cases each in stagesⅠ-ⅢA andⅢB-Ⅳ)and 10 healthy subjects(control group)were selected.Flow cytometry was used to detect peripheral blood NK cell activating receptors NKG2D,NCRs(NKp30,NKp44,NKp46)and inhibitory receptors CD158a,CD158b,CD158e,and receptor expression after two cycles of chemotherapy of stagesⅢB toⅣ.CD56^dim and CD56 bright were counted according to the expression intensity of CD56.Results The CD56^dim activated receptors NKG2D and NKp30 in patients with stageⅢB-Ⅳin non-small cell lung cancer were lower than those in healthy subjects and patients in stageⅠ-ⅢA,the expression of CD56^dim activated receptor NKp44 of non-small cell lung cancer in stageⅠ-ⅢA andⅢB-Ⅳwas lower than that of healthy subjects(P<0.05).There was no significant difference between three groups in CD56^dim activated receptor NKp46(P>0.05).There was no significant difference between the three groups in the expression of NKG2D,NKp30,NKp44 and NKp46(P>0.05).There was no significant difference in the CD56^dim inhibitory receptors CD158a,CD158b,CD158e and CD56 bright inhibitory receptors CD158a,CD158b,and CD158e in three groups(P>0.05).Due to the lack of enrolled staff,14 patients were enrolled after two cycles chemotherapy of stageⅢB toⅣ.The percentages of CD56^dim activated receptors NKp30 and NKp44 in patients with stageⅢB-Ⅳnon-small cell lung cancer after chemotherapy were higher than those before treatment(P<0.05).After chemotherapy,CD56^dim activating receptors NKp46,NKG2D and inhibitory receptors CD158a,CD158b,CD158e were not statistically different from those before chemotherapy(P>0.05).After chemotherapy,there was no significant difference in the activation receptor NKp30,NKp44,NKp46,NKG2D and the inhibition receptor CD158a,CD158b and CD158e between two groups(P>0.05).After 2 cycles of chemotherapy,the PR rate of 14 patients reached 78.5%(11/14).Conclusion The decreased expression of activated receptors in CD56^dim NK cells in stageⅢB-Ⅳmay be related to the decreased cytotoxicity of activated receptors on NK cells caused by tumor microenvironment.After chemotherapy,the expression of NKp30 and NKp44 can be increased.It is speculated that chemotherapy can play its killing effect on tumor by improving the activity of NK cells.