摘要
目的观察肝癌患者术后单用白细胞介素2（IL-2）培养和IL-12＋IL-2培养的自体肝癌肿瘤浸润淋巴细胞（TIL）输注后，其特异性杀伤力、增殖能力、细胞因子的改变以及细胞免疫功能和临床症状的变化。方法将手术切除的原发性肝癌组织进行体外分离，分别用含IL-2的培养液和含IL-12＋IL-2的培养液培养，诱导TIL的生长。培养10～14d测定细胞杀伤率、细胞因子和增殖能力，待细胞扩增达10^8-9／ml时进行输注，随访观察临床疗效。结果①输注IL-12＋IL-2组TIL对自体肝癌细胞的细胞杀伤率、细胞扩增能力、细胞因子IFN-γ和TNF-α水平均比IL-2组明显增高；②输注IL-12＋IL-2诱导的TIL组与IL-2诱导的TIL组输注后CD3^＋、CD4^＋、CD8^＋均升高，以CD3^＋、CD8^＋升高为主。与输注前比较，差异均有统计学意义；IL-12＋IL-2组与IL-2组间比较，前者CD3^＋、CD8^＋、CD56^＋上明显高于后者，差异均有统计学意义。③输注后两组患者的临床症状均比输注前改善明显，但两组间比较无明显差异。④接受TIL自体输注治疗的患者，其1年、3年、5年生存率均有所提高，IL-12＋IL-2组与IL-2组与同期非TIL治疗组相比较（P〈0．05）。结论白介素12诱导肝癌TIL可明显增强TIL细胞的特异性细胞毒作用且增殖能力明显增强。肝癌患者术后输注IL-12＋IL-2诱导的自体肝癌肿瘤浸润淋巴细胞比输注IL-2诱导的肝癌肿瘤浸润淋巴细胞能更有效地提高肝癌患者机体免疫机能，延长1年生存期，减少复发。
Objective To investigate the effects of the tumor infiltrating lymphocytes （TILs） from primary hepatic carcinoma （ PHC ） induced by interleukin-12 （ IL-12 ） with IL-2, on their cytotoxicity, proliferation, and cytokine production, and the immunological function and survival of the PHC patients. Methods PHC cells and TILs were isolated from the resected tumors and cultured. IL-2 was added into the culture medium with or without IL-12. Ten to 14 days later the eytotoxie activity and proliferation index （PI） of the TILs were calculated. The levels of the cytokine interferon （IFR）-γ and tumor necrosis factor （TNF）- α in the supernatant were tested by ELISA. 20 - 25 days after the operation the TILs were re-infused into the bodies. The clinical manifestation, cytotoxicity of TILs, phenotype of peripheral blood lymphocytes, and survival of patients were observed. Results （1）The cytotoxicity of the TILs of the IL-12 ＋ IL-2 group against the autologous hepatic carcinoma cells was greater than that of the TILs of the IL-2 group （P 〈 0.05 ）. （2） The PI of the TILs of the IL-12 ＋ IL-2 group was 17.78%, significantly higher than that of the IL-2 group （ 10.9%, P 〈0.05）. （3）The levels of IFN-γ and TNF-α of the IL-12 ＋ IL-2 group were （2180 ＋494） pg/ ml and（485 ± 98） pg/ml, both significantly higher than those of the IL-2 group [ （ 1078 ± 309.46） pg/ml and （422.00±15.81） pg/ml, both P〈0.05]. （4） After re-infusion of TILs, the CD3＋ , CDs＋ , CD4~ , and CD56 ＋ rates, especially the CD3^＋ and CD8^＋ rates, of the IL-12 ＋ IL-2 group were all signifieandy higher than those of the IL-2 group （ all P 〈 0.05）. （5） After TIL re-infusion the elinieal manifestation of all patients were improved. （6） 23 of the 25 patients receiving the re-infusion of the TILs of the IL-12 ＋ IL-2 group survived for more than 1 year, with a rate signifieandy higher than that of the IL-2 group （ 17/25, Χ^2 = 4.5, P 〈 0.05 ） , however, there
出处
《中华医学杂志》
CAS
CSCD
北大核心
2008年第14期973-976,共4页
National Medical Journal of China
关键词
肝细胞癌
肿瘤浸润淋巴细胞
免疫治疗
白细胞介素12
Primary hepatic carcinoma （ PHC ）
tumor infiltrating lymphocytes （ TIL ）
Immunotherapy
Interleukin-2 （IL-12）
