Isopentenyl pyrophosphate-activated CD56+ {gamma}{delta} T lymphocytes display potent antitumor activity toward human squamous cell carcinoma.
Isopentenyl pyrophosphate-activated CD56+ {gamma}{delta} T lymphocytes display potent antitumor activity toward human squamous cell carcinoma.
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DOI：
10.1158/1078-0432.ccr-07-4912
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发表时间：
2008-07-01
期刊：
影响因子：
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通讯作者：
Chapoval AI
中科院分区：
文献类型：
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作者：
Alexander AA;Maniar A;Cummings JS;Hebbeler AM;Schulze DH;Gastman BR;Pauza CD;Strome SE;Chapoval AI
αβ T淋巴细胞上CD 56（一种自然杀伤（NK）细胞相关分子）的表达与其增强的抗肿瘤效应功能相关。CD 56也在γδ T细胞的亚群上表达。然而，CD 56 + γδ T细胞的抗肿瘤效应子功能的特征很差。为了研究CD 56 + γδ T细胞在肿瘤杀伤中的潜在效应器作用，我们使用来自健康供体的PBMC的异戊烯基焦磷酸（IPP）和IL-2扩增的γδ T细胞。30%至70%的IPP+IL-2扩增的γδ T细胞在其表面上表达⑶ 56。有趣的是，虽然CD 56+和CD 56 − γδ T细胞表达的参与调节γδ T细胞细胞毒性的受体水平相当（例如NKG 2D和CD 94），但只有CD 56 + γδ T淋巴细胞能够杀死鳞状细胞癌（SCC）和其他实体瘤细胞系。这种效应可能是由溶细胞颗粒的释放增强介导的，因为在暴露于肿瘤细胞系后，与CD 56 −对照相比，CD 56 + γδ T淋巴细胞表达更高水平的CD 107 a。肿瘤细胞系的裂解被康卡霉素A和抗γδTCR +抗NKG 2D mAb的组合阻断，表明CD 56 + γδ T细胞的裂解活性涉及穿孔素-颗粒酶途径，并且主要依赖于γδTCR/NKGD 2。重要的是，表达CD 56的γδ T淋巴细胞对Fas配体和化学诱导的凋亡具有抗性。我们的数据表明，CD 56 + γδ T细胞是一种有效的抗肿瘤效应细胞，能够杀死SCC，并可能在头颈癌和其他恶性肿瘤患者中发挥重要的治疗作用。
The expression of CD56, a natural killer (NK) cell-associated molecule, on αβ T lymphocytes correlates with their increased anti-tumor effector function. CD56 is also expressed on a subset of γδ T cells. However, anti-tumor effector functions of CD56+ γδ T cells are poorly characterized. To investigate the potential effector role of CD56+ γδ T cells in tumor killing, we employed isopentenyl pyrophosphate (IPP) and IL-2 expanded γδ T cells from PBMC of healthy donors. Thirty to 70% of IPP+IL-2 expanded γδ T cells express CD56 on their surface. Interestingly, while both CD56+ and CD56− γδ T cells express comparable levels of receptors involved in the regulation of γδ T cell cytotoxicity (e.g. NKG2D and CD94) only CD56+ γδ T lymphocytes are capable of killing squamous cell carcinoma (SCC) and other solid tumor cell lines. This effect is likely mediated by the enhanced release of cytolytic granules, since CD56+ γδ T lymphocytes expressed higher levels of CD107a compared to CD56− controls, following exposure to tumor cell lines. Lysis of tumor cell lines is blocked by concanomycin A and a combination of anti-γδTCR + anti-NKG2D mAb, suggesting that the lytic activity of CD56+ γδ T cells involves the perforin-granzyme pathway and is mainly γδTCR/NKGD2 dependent. Importantly, CD56 expressing γδ T lymphocytes are resistant to Fas ligand and chemically induced apoptosis. Our data indicate that CD56+ γδ T cells are potent anti-tumor effectors capable of killing SCC and may play an important therapeutic role in patients with head and neck cancer and other malignancies.