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[过继性免疫治疗与肾转移性癌。白细胞介素-4对肿瘤浸润淋巴细胞(TIL)的调节作用]

[Adoptive immunotherapy and metastasized cancer of the kidney. Regulator effects of interleukin-4 on tumor infiltrating lymphocytes (TIL)].

作者信息

Peyret C, Bochner B, Lee T Y, Tso C L, Dekernion J B, Belldegrun A

机构信息

Service d'Urologie, hôpital Cochin, Paris.

出版信息

Chirurgie. 1991;117(9):700-9.

PMID:1843670
Abstract

Adoptive immunotherapy is a new therapeutic approach of the treatment of advanced renal cell cancer. Experimental studies have shown that the cells with the highest cytolytic activity are tumor infiltrating lymphocytes (TIL). The effects of interleukin-4 (IL-4) on the expansion, proliferation, phenotype and antitumor activity of TIL were studied. Cultures were obtained from three primary renal tumors and one group of tumor invaded, regional lymph nodes. IL-4 induced a significant increase in lymphocytes expansion and proliferation, but the response was dependent of the concurrent dose of IL-2 in culture. TIL grown in the presence of IL-4 significantly reduced the level of non specific, non MHC restricted antitumor activity while exhibiting no effect on the level of autologous killing. The effects of irradiated autologous tumor stimulation on TIL cultures were also evaluated. Addition of autologous tumor increased expansion and proliferation of all cultures and significantly enhanced levels of autologous killing. IL-4 and autologous tumor stimulation are effective growth factors when used in combination with a lose dose IL-2 regimen and may be of significant benefit in the expansion of TIL for clinical trials.

摘要

过继性免疫疗法是治疗晚期肾细胞癌的一种新的治疗方法。实验研究表明,具有最高细胞溶解活性的细胞是肿瘤浸润淋巴细胞(TIL)。研究了白细胞介素-4(IL-4)对TIL的扩增、增殖、表型和抗肿瘤活性的影响。培养物取自三个原发性肾肿瘤和一组肿瘤浸润的区域淋巴结。IL-4诱导淋巴细胞扩增和增殖显著增加,但该反应依赖于培养物中IL-2的同时剂量。在IL-4存在下生长的TIL显著降低了非特异性、非MHC限制性抗肿瘤活性水平,而对自体杀伤水平无影响。还评估了辐照自体肿瘤刺激对TIL培养物的影响。添加自体肿瘤可增加所有培养物的扩增和增殖,并显著提高自体杀伤水平。当与低剂量IL-2方案联合使用时,IL-4和自体肿瘤刺激是有效的生长因子,可能对TIL的扩增用于临床试验有显著益处。

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