Lotzová E, Savary C A, Freedman R S, Edwards C L, Wharton J T
Department of General Surgery, University of Texas System Cancer Center, M.D. Anderson Hospital and Tumor Institute, Houston 77030.
Int J Cancer. 1988 Aug 15;42(2):225-31. doi: 10.1002/ijc.2910420214.
We investigated the ability of endogenous and recombinant interleukin-2 (IL-2)-stimulated NK cells from normal donors and ovarian cancer patients to mediate lysis of ovarian tumors, and found that peripheral blood (PB) mononuclear cells of normal donors or cancer patients did not display tumoricidal activity against ovarian cell line or fresh ovarian tumors. In addition, ovarian cancer patients displayed a defect in NK-cell activity against the highly NK-sensitive target, K-562. However, lytic activity against ovarian tumors (including cultured and primary tumors) was induced and that against K-562 was potentiated in PB of normal donors and PB and peritoneal cavity of ovarian cancer patients after enrichment of LGL on Percoll density gradient or after stimulation of effector cells with recombinant IL-2 in vitro. The IL-2-generated cytotoxic cells in PB were characterized as NK cells displaying CD16+, NKH1 (Leu-19)+, CD3- and CD5- phenotype, while those in the peritoneal cavity were predominantly CD16-, NKH1+, CD3- and CD5-. Studies on the mechanism of IL-2-dependent generation of cytotoxicity showed that such an effect was mediated via recruitment of tumor-binding cells as well as by an increase in the frequency of cytotoxic cells.
我们研究了来自正常供体和卵巢癌患者的内源性和重组白细胞介素-2（IL-2）刺激的自然杀伤（NK）细胞介导卵巢肿瘤细胞溶解的能力，发现正常供体或癌症患者的外周血（PB）单核细胞对卵巢癌细胞系或新鲜卵巢肿瘤均无杀瘤活性。此外，卵巢癌患者对高度NK敏感靶细胞K-562的NK细胞活性存在缺陷。然而，在通过Percoll密度梯度富集大颗粒淋巴细胞（LGL）后，或在体外使用重组IL-2刺激效应细胞后，正常供体的PB以及卵巢癌患者的PB和腹腔中，针对卵巢肿瘤（包括培养的肿瘤和原发性肿瘤）的溶解活性被诱导，针对K-562的溶解活性增强。PB中IL-2产生的细胞毒性细胞被鉴定为具有CD16 +、NKH1（Leu-19）+、CD3 - 和CD5 - 表型的NK细胞，而腹腔中的细胞毒性细胞主要为CD16 -、NKH1 +、CD3 - 和CD5 -。对IL-2依赖性细胞毒性产生机制的研究表明，这种效应是通过募集肿瘤结合细胞以及增加细胞毒性细胞的频率来介导的。
