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首页> 外文期刊>Clinical immunology: The official journal of the Clinical Immunology Society >Adoptive transfer of natural killer cells promotes the anti-tumor efficacy of T cells
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Adoptive transfer of natural killer cells promotes the anti-tumor efficacy of T cells

机译：采用自然杀伤细胞促进T细胞的抗肿瘤疗效

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The density of NK cells in tumors correlates positively with prognosis in many types of cancers. The average number of infiltrating NK cells is, however, quite modest (approximately 30 NK cells/sq.mm), even in tumors deemed to have a "high" density of infiltrating NK cells. It is unclear how such low numbers of tumor-infiltrating NK cells can influence outcome. Here, we used ovalbumin-expressing tumor cell lines and TCR transgenic, OVA-specific cytotoxic T lymphocytes (OT-I-CTLs) to determine whether the simultaneous attack by anti-tumor CTLs and IL-2-activated NK (A-NK) cells synergistically increases the overall tumor cell kill and whether upregulation of tumor MHC class-I by NK cell-derived interferon-gamma (IFN gamma) improves tumor-recognition and kill by anti-tumor CTLs. At equal E:T ratios, A-NK cells killed OVA-expressing tumor cells better than OT-I-CFLs. The cytotoxicity against OVA-expressing tumor cells increased by combining OT-I-CTLs and A-NK cells, but the increase was additive rather than synergistic. A-NK cells adenovirally-transduced to produce IL-12 (A-NKIL-12) produced high amounts of IFN gamma. The addition of a low number of A-NKIL-12 cells to OT-I-CTLs resulted in a synergistic, albeit modest, increase in overall cytotoxicity. Pre-treatment of tumor cells with NK cell-conditioned medium increased tumor MHC expression and sensitivity to CTL-mediated killing. Pre-treatment of CTLs with NK cell-conditioned medium had no effect on CTL cytotoxicity. In vivo, MHC class-I expression by OVA-expressing B16 melanoma lung metastases increased significantly within 24-48 h after adoptive transfer of A-NKIL-12 cells. OT-I-CTLs and A-NKIL-12 cells localized selectively and equally well into OVA-expressing B16 lung metastases and treatment of mice bearing 7-days-old OVA-B16 lung metastases with both A-NKIL-12 cells and OT-I-CTLs lead to a significant prolongation of survival.
机译：肿瘤中NK细胞的密度随着许多类型的癌症中的预后与预后相关。然而，即使在被认为具有“高”密度的渗透NK细胞的肿瘤中，平均渗透NK细胞的平均渗透数量是相当温和的（约30个NK细胞/ SQ.mm）。目前尚不清楚这些低数量的肿瘤渗透NK细胞可以影响结果。在此，我们使用卵磷酸蛋白表达肿瘤细胞系和TCR转基因，卵巢特异性细胞毒性T淋巴细胞（OT-I-CTL）以确定抗肿瘤CTL和IL-2活化NK（A-NK）的同时攻击细胞协同增加了整个肿瘤细胞杀灭，NK细胞衍生的干扰素-γ（IFNγ）的肿瘤MHC类-i的上调是否改善了抗肿瘤CTL的肿瘤识别和杀死。在等于e：T比率，优于OT-I-CFL，A-NK细胞杀死了表达OVA表达的肿瘤细胞。通过组合OT-I-CTL和A-NK细胞来增加针对卵子表达肿瘤细胞的细胞毒性，但增加是添加剂而不是协同作用。 A-NK细胞腺瘤细胞转导产生IL-12（A-NKIL-12）产生大量IFNγ。向OT-I-CTL添加少量的A-NKIL-12细胞导致协同，尽管适度，总体细胞毒性增加。用NK细胞调节培养基提高肿瘤细胞的预处理增加了肿瘤MHC表达和对CTL介导的杀灭的敏感性。用NK细胞条件培养基的CTL预处理对CTL细胞毒性没有影响。在通过OVA表达的B16黑色素瘤肺转移的MHC类-I表达在继承A-NKIL-12细胞后24-48小时内显着增加。 OT-I-CTL和A-NKIL-12细胞选择性地局限性，同样良好地定位在oVA表达的B16肺转移和用A-NKIL-12细胞和OT-携带7天历史的OVA-B16肺转移的小鼠的处理。 I-CTLS导致延长存活率。

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