CAJ | 학술논문

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10-14 d测定细胞杀伤率、细胞因子和增殖能力,待细胞扩增达108-9/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+、CIM+、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+、CD 56+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.
목적 관찰간암환자술후단용백세포개소2(IL-2)배양화IL-12+IL-2배양적자체간암종류침윤림파세포(TIL)수주후,기특이성살상력、증식능력、세포인자적개변이급세포면역공능화림상증상적변화.방법 장수술절제적원발성간암조직진행체외분리,분별용함IL-2적배양액화함IL-12+IL-2적배양액배양,유도TIL적생장.배양10-14 d측정세포살상솔、세포인자화증식능력,대세포확증체108-9/ml시진행수주,수방관찰림상료효.결과 ①수주IL-12+IL-2조TIL대자체간암세포적세포살상솔、세포확증능력、세포인자IFN-γ화TNF-α수평균비IL-2조명현증고;②수주IL-12+IL-2유도적TIL조여IL-2유도적TIL조수주후CD3+、CIM+、CD8+균승고,이CD3+、CD8+승고위주.여수주전비교,차이균유통계학의의;IL-12+IL-2조여IL-2조간비교,전자CD3+、CD8+、CD 56+상명현고우후자,차이균유통계학의의.③수주후량조환자적림상증상균비수주전개선명현,단량조간비교무명현차이.④접수TIL자체수주치료적환자,기1년、3년、5년생존솔균유소제고,IL-12+IL-2조여IL-2조여동기비TIL치료조상비교(P＜0.05).결론 백개소12유도간암TIL가명현증강TIL세포적특이성세포독작용차증식능력명현증강.간암환자술후수주IL-12+IL-2유도적자체간암종류침윤림파세포비수주IL-2유도적간암종류침윤림파세포능경유효지제고간암환자궤체면역궤능,연장1년생존기,감소복발.
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 cytotoxic 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 the autologous hepatic carcinoma cells was greater than that of the TILs of the IL-2 group(P＜0. 05). ml and(485±98)pg/ml, both significantly higher than those of the IL-2 group[(1078±309. 46)pg/ml and CD56+ rates, especially the CD3+ and CD8+ rates, of the IL-12+IL-2 group were all significantly group survived for more than 1 year, with a rate significantly higher than that of the IL-2 group(17/25, x2=4. 5, P＜0. 05), however, there were no significant differences in the 3-year and 5-year survival rates between these 2 groups(both P＞0. 05). The number of patients who showed recurrence in less than 1 year was 17 in the IL-2 group, with a rate significantly higher that of the IL-12+IL-2 group(8/25, X2=4. 32, P＜0. 05). However, there was no significant difference in the recurrence rate ≤3 years between these 2 groups(x2=1. 56, P＞0. 05). Conclusion TILs from primary hepatic carcinoma induced by IL-12 can obviously enhance specific cytotoxicity and proliferation of TILs. TILs induced by IL-12+IL-2 increase the patients'immunological function, prolong the 1-year survival, and decreases recurrence more effectively than the TILs induced by IL-2 only.