Institut National de la Santé et de la Recherche Medicale U753, Team 1: Tumor Antigens and T-cell Reactivity, Integrated Research Cancer Institute in Villejuif, Institut de Cancérologie Gustave Roussy, Villejuif, France.
Cancer Res. 2012 Dec 15;72(24):6325-32. doi: 10.1158/0008-5472.CAN-12-2027. Epub 2012 Dec 7.
Immune system-mediated eradication of neoplastic cells requires induction of a strong long-lasting antitumor T-cell response. However, generation of tumor-specific effector T cells does not necessarily result in tumor clearance. CTL must first be able to migrate to the tumor site, infiltrate the tumor tissue, and interact with the target to finally trigger effector functions indispensable for tumor destruction. Chemokines are involved in circulation, homing, retention, and activation of immunocompetent cells. Although some of them are known to contribute to tumor growth and metastasis, others are responsible for changes in the tumor microenvironment that lead to extensive infiltration of lymphocytes, resulting in tumor eradication. Given their chemoattractive and activating properties, a role for chemokines in the development of the effector phase of the antitumor immune response has been suggested. Here, we emphasize the role of the chemokine-chemokine receptor network at multiple levels of the T-cell-mediated antitumor immune response. The identification of chemokine-dependent molecular mechanisms implicated in tumor-specific CTL trafficking, retention, and regulation of their in situ effector functions may offer new perspectives for development of innovative immunotherapeutic approaches to cancer treatment.
免疫系统介导的肿瘤细胞消除需要诱导强烈的、持久的抗肿瘤 T 细胞反应。然而，产生肿瘤特异性效应 T 细胞并不一定能导致肿瘤清除。CTL 必须首先能够迁移到肿瘤部位，渗透到肿瘤组织中，并与靶细胞相互作用，最终触发对肿瘤破坏至关重要的效应功能。趋化因子参与免疫细胞的循环、归巢、保留和激活。虽然其中一些趋化因子已知有助于肿瘤生长和转移，但其他趋化因子则负责改变肿瘤微环境，导致淋巴细胞广泛浸润，从而消除肿瘤。鉴于趋化因子具有趋化性和激活特性，有人提出趋化因子在抗肿瘤免疫反应的效应阶段的发展中起作用。在这里，我们强调了趋化因子-趋化因子受体网络在 T 细胞介导的抗肿瘤免疫反应的多个水平上的作用。鉴定与肿瘤特异性 CTL 迁移、保留和调节其原位效应功能相关的趋化因子依赖性分子机制，可能为开发创新的癌症治疗免疫治疗方法提供新的视角。
