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目的研究肿瘤浸润淋巴细胞生物治疗中淋巴细胞端粒酶活性 (telom erase activation,TA)变化的情况。方法分离患者肿瘤浸润淋巴细胞以 IL - 2体外扩增后回输患者 ,同时随访疗效。应用 TRAP- PCR检测 TA。结果发现肿瘤浸润淋巴细胞的 TA明显高于肿瘤未浸润淋巴细胞 TA(t=2 .819,P<0 .0 5 ) ,体外扩增淋巴细胞的 TA0 .0 82± 0 .0 14明显高于肿瘤未浸润淋巴细胞 TA 0 .0 2 6± 0 .0 0 6 (t=12 .81,P<0 .0 1)。回输 30 d后的淋巴细胞 TA与扩增前的肿瘤浸润淋巴细胞 TA接近。端粒酶阳性扩增肿瘤浸润淋巴细胞生物治疗缓解率 5 6 .2 5 %与有效率 75 .0 0 %明显高于端粒酶阴性的扩增肿瘤浸润淋巴细胞生物治疗缓解率 30 .0 0 %与有效率 5 0 .0 0 %。结论增殖培养可引起肿瘤浸润淋巴细胞端粒酶活性的改变 ,选择端粒酶阳性的体外扩增肿瘤浸润淋巴细胞进行生物治疗有希望进一步提高恶性肿瘤患者的生存率
Objective To study the changes of telomerase activity (TA) in lymphocyte biotherapy of tumor infiltrating lymphocytes. METHODS: Patients with tumor-infiltrating lymphocytes were isolated and transferred back to patients after IL-2 expansion in vitro. The efficacy was followed up. TRAP-PCR was used to detect TA. The results showed that the TA of tumor-infiltrating lymphocytes was significantly higher than that of tumor-infiltrating lymphocytes (t=2.819, P<0.05). The TA0.882±0.14 of lymphocytes expanded in vitro was significantly higher than that of tumor-infiltrating lymphocytes. Tumor non-infiltrating lymphocytes were TA 0 .0 2 6± 0 . 0 0 6 (t=12.81, P<0.01). After 30 days of reinfusion, lymphocyte TA was close to the pre-expansion tumor infiltrating lymphocyte TA. The response rate of telomerase-positive amplification of tumor-infiltrating lymphocytes was 56.25% and the effective rate was 75.00%. It was significantly higher than that of telomerase-negative tumor-infiltrating lymphocytes biotherapy. 30. 0 0 % and efficiency 5.00%. Conclusion Proliferation culture can cause changes in telomerase activity in tumor-infiltrating lymphocytes. Selective telomerase-enhanced in vitro expansion of tumor-infiltrating lymphocytes for biological therapy promises to further improve the survival rate of patients with malignant tumors.