Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. Department of Pathology, University of Melbourne, Parkville, Australia. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia.
Cancer Immunology Program, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. Department of Pathology, University of Melbourne, Parkville, Australia. Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia. Department of Immunology, Monash University, Clayton, Australia.
Cancer Res. 2014 Dec 15;74(24):7168-74. doi: 10.1158/0008-5472.CAN-14-2458. Epub 2014 Dec 4.
T cells are a crucial component of the immune response to infection and cancer. In addition to coordinating immunity in lymphoid tissue, T cells play a vital role at the disease site, which relies on their efficient and specific trafficking capabilities. The process of T-cell trafficking is highly dynamic, involving a series of distinct processes, which include rolling, adhesion, extravasation, and chemotaxis. Trafficking of T cells to the tumor microenvironment is critical for the success of cancer immunotherapies such as adoptive cellular transfer. Although this approach has achieved some remarkable responses in patients with advanced melanoma and hematologic malignancy, the success against solid cancers has been more moderate. One of the major challenges for adoptive immunotherapy is to be able to effectively target a higher frequency of T cells to the tumor microenvironment, overcoming hurdles associated with immunosuppression and aberrant vasculature. This review summarizes recent advances in our understanding of T-cell migration in solid cancer and immunotherapy based on the adoptive transfer of natural or genetically engineered tumor-specific T cells and discusses new strategies that may enhance the trafficking of these cells, leading to effective eradication of solid cancer and metastases.
T 细胞是感染和癌症免疫反应的关键组成部分。除了在淋巴组织中协调免疫外，T 细胞在疾病部位也发挥着至关重要的作用，这依赖于它们高效和特异的归巢能力。T 细胞归巢的过程是高度动态的，涉及一系列不同的过程，包括滚动、黏附、渗出和趋化。T 细胞向肿瘤微环境的迁移对于癌症免疫疗法的成功至关重要，如过继细胞转移。尽管这种方法在晚期黑色素瘤和血液恶性肿瘤患者中取得了一些显著的疗效，但在实体瘤中的疗效较为温和。过继免疫疗法的主要挑战之一是能够有效地将更高频率的 T 细胞靶向肿瘤微环境，克服与免疫抑制和异常血管有关的障碍。本综述总结了近年来我们对实体瘤中 T 细胞迁移和基于过继转移天然或基因工程肿瘤特异性 T 细胞的免疫治疗的理解的最新进展，并讨论了可能增强这些细胞归巢的新策略，从而有效消除实体瘤和转移。
