Microscopical Imaging of the Cell, Nijmegen Center for Molecular Life Sciences, Radboud University Nijmegen, The Netherlands.
Immunol Lett. 2011 Jul;138(1):19-21. doi: 10.1016/j.imlet.2011.02.016. Epub 2011 Feb 17.
Immunological control of cancer lesions requires local uptake of tumor-specific antigen followed by the activation and expansion of tumor specific cytotoxic T-lymphocytes (CTL). An efficient effector phase further depends upon the entry of activated CTL into the tumor microenvironment and scanning of tumor tissue, which leads to direct interaction of the CTL with target cells followed by apoptosis induction and shrinkage of the tumor lesion. Whereas the antigens and pathways that lead to efficient activation of tumor-specific CTL are well established, the local mechanisms that enable efficient - or deficient - CTL function in the tumor tissue are poorly understood. Firstly, effector T lymphocytes need to be mobile to reach the tumor lesion. Next, they must physically interact with and scan tumor cells for antigenic MHC/peptide complexes. Lastly, CTLs must undergo activation and functional conjugation with target cells to induce apoptosis either by the release of perforins or the engagement of Fas/FasL. All these steps of effector function are interdependent and require the amoeboid migration of CTL through tissue to reach, engage with and leave encountered cells.
癌症病变的免疫控制需要肿瘤特异性抗原的局部摄取，随后激活和扩增肿瘤特异性细胞毒性 T 淋巴细胞 (CTL)。有效的效应期进一步取决于激活的 CTL 进入肿瘤微环境和扫描肿瘤组织，这导致 CTL 与靶细胞的直接相互作用，随后诱导靶细胞凋亡和肿瘤病变缩小。虽然导致肿瘤特异性 CTL 有效激活的抗原和途径已经得到很好的确定，但在肿瘤组织中实现有效或缺陷 CTL 功能的局部机制还知之甚少。首先，效应 T 淋巴细胞需要能够移动才能到达肿瘤病变部位。接下来，它们必须与肿瘤细胞进行物理相互作用，并扫描抗原 MHC/肽复合物。最后，CTL 必须与靶细胞激活和功能共轭，通过释放穿孔素或 Fas/FasL 的结合来诱导凋亡。效应功能的所有这些步骤都是相互依赖的，需要 CTL 通过组织进行变形运动，以到达、与遇到的细胞结合并离开。
