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目的:研究γδT和Th17细胞在肝细胞癌(HCC)组织及外周血中的表达,探讨T细胞子集在肝细胞癌(HCC)微环境中变化的意义。方法:ELISA方法检测51例HCC患者和30例正常对照组血中IL-17、IL-23、IFN-γ浓度;并采用流式细胞术检测其中的34例手术患者的外周血单个核细胞(PBMC)及癌组织、癌旁肝组织中IL-17~+γδT和Th17的水平。结果:HCC患者血清IL-17、IL-23浓度随肿瘤TNM分期的增加而升高,且IL-17随着肿瘤的进展升高更显著(P<0.01);而IFN-γ水平则降低,与对照组比较均有显著差异(P<0.01);HCC患者外周血PBMC、非肿瘤浸润淋巴细胞(NIL)和肿瘤浸润淋巴细胞(TIL)中Th17分别为(2.82±0.52)%、(4.39±1.19)%和(6.08±1.39)%,比较有显著差异(P<0.05和P<0.01);HCC患者外周血PBMC、NIL和TIL中IL-17~+γδT分别为(3.41±0.47)%、(6.03±1.34)%和(10.27±1.52)%,比较有显著差异(P<0.01)。Th17和IL-17~+γδT细胞随着肿瘤的进展,Ⅰ、Ⅱ、Ⅲ、Ⅳ期期肿瘤组织中IL-17~+γδT浸润数目分别为(6.70±1.04)%、(6.91±1.07)%、(8.70±2.28)%、(10.13±2.05)%,Ⅲ、Ⅳ期与Ⅰ、Ⅱ期比较有显著差异(P<().01)。结论:HCC患者血清中IL-17浓度升高与癌组织及癌旁组织中γδT和Th17细胞浸润有关;在肿瘤生长的微环境中,γδT细胞可能是促进而不是抗肿瘤的效应细胞,IL-17浓度随TNM分期的增加而升高,IL-17可能促进了HCC的血管形成和肿瘤的增殖、侵袭和远处转移;γδT细胞在肿瘤微环境中浸润产生极少量的IFN-γ,致细胞毒功能下降,抑制了机体对肿瘤细胞的免疫监视功能。
Objective: To investigate the expression of γδT and Th17 cells in hepatocellular carcinoma (HCC) tissues and peripheral blood and to explore the significance of T cell subsets in hepatocellular carcinoma (HCC) microenvironment. Methods: The levels of IL-17, IL-23 and IFN-γ in 51 HCC patients and 30 normal controls were detected by ELISA. Flow cytometry was used to detect the levels of peripheral blood mononuclear cells PBMC), as well as the levels of IL-17 ~ + γδT and Th17 in the adjacent tissues. Results: The serum levels of IL-17 and IL-23 in HCC patients increased with the increase of TNM staging, and IL-17 increased more significantly with tumor progression (P <0.01); while the level of IFN-γ decreased, (2.82 ± 0.52)% and (4.39 ±)% respectively in PBMC, non-tumor infiltrating lymphocytes (NIL) and tumor infiltrating lymphocytes (TIL) IL-17 ~ + γδT in PBMC, NIL and TIL were (3.41 ± 0.47)%, 1.19% and (6.08 ± 1.39)%, respectively (6.03 ± 1.34)% and (10.27 ± 1.52)%, respectively, with significant difference (P <0.01). The numbers of IL-17 ~ + γδT infiltration in tumor tissues of stage Ⅰ, Ⅱ, Ⅲ and Ⅳ were (6.70 ± 1.04)% and (6.91 ± 1.07)% respectively with the progression of Th17 and IL-17 ~ + γδT cells. , (8.70 ± 2.28)% and (10.13 ± 2.05)%, respectively. There was a significant difference between stage Ⅲ and Ⅳ and stage Ⅰ and Ⅱ (P <(subscript 0)). CONCLUSIONS: Elevated serum IL-17 levels in HCC patients are related to the infiltration of γδT and Th17 cells in cancer tissues and paracancerous tissues. In the microenvironment of tumor growth, γδT cells may be the effector cells rather than antitumor cells. IL- 17 concentration increased with the increase of TNM staging, IL-17 may promote the angiogenesis of HCC and tumor proliferation, invasion and distant metastasis; γδ T cells infiltrated in the tumor microenvironment produced a very small amount of IFN-γ, induced cells Decreased toxic function, inhibit the body’s immune surveillance of tumor cells.