Institut National de la Santé et de la Recherche Médicale (INSERM) U753, Laboratoire Immunologie des tumeurs humaines: Interaction effecteurs cytotoxiques-système tumoral, Integrated Research Cancer Institute in Villejuif (IRCIV), Institut de Cancérologie Gustave Roussy (IGR), Villejuif, France.
Cancer Res. 2011 Jan 15;71(2):328-38. doi: 10.1158/0008-5472.CAN-10-2457. Epub 2011 Jan 11.
Interaction of the integrin αE(CD103)β7 expressed on tumor-infiltrating lymphocytes (TIL) with E-cadherin on epithelial tumor cells is required to trigger polarized exocytosis of cytotoxic granules in TIL that elicit tumor cell lysis. In this study, we investigated the functional and signaling properties of CD103 and its individual contribution to T-cell-mediated cancer-cell killing. Our results indicated that the binding of CD103 on tumor-specific CTL to immobilized recombinant E-cadherin-Fc is sufficient to induce the polarization of cytolytic granules, whereas the degranulation of cytolytic granules also requires the coengagement of the T-cell receptor. Moreover, minimal CD103 triggering promotes the phosphorylation of the ERK1/2 kinases and phospholipase Cγ1 (PLCγ1). Inhibiting PLCγ blocks granule relocalization, decreasing T-cell receptor-mediated cytotoxicity. Thus, our results emphasize a unique costimulatory role of CD103 in tumor-specific CTL activation by providing signals that promote T-cell effector functions needed to specifically target and lyse cancer cells.
肿瘤浸润淋巴细胞（TIL）表面表达的整合素 αE（CD103）β7 与上皮肿瘤细胞上的 E-钙黏蛋白相互作用，可触发 TIL 中细胞毒性颗粒的极化胞吐，从而引发肿瘤细胞裂解。在这项研究中，我们研究了 CD103 的功能和信号特性及其对 T 细胞介导的癌细胞杀伤的单独贡献。我们的结果表明，肿瘤特异性 CTL 上的 CD103 与固定化重组 E-钙黏蛋白-Fc 的结合足以诱导细胞毒性颗粒的极化，而细胞毒性颗粒的脱颗粒也需要 T 细胞受体的共结合。此外，最小的 CD103 触发可促进 ERK1/2 激酶和磷脂酶 Cγ1（PLCγ1）的磷酸化。抑制 PLCγ 可阻止颗粒重定位，从而降低 T 细胞受体介导的细胞毒性。因此，我们的结果强调了 CD103 在肿瘤特异性 CTL 激活中的独特共刺激作用，通过提供促进 T 细胞效应功能的信号，这些信号对于特异性靶向和裂解癌细胞是必需的。
