Current concepts of tumor-infiltrating lymphocytes in human malignancies
Current concepts of tumor-infiltrating lymphocytes in human malignancies
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DOI：
10.1016/j.jri.2005.06.002
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发表时间：
2005-10-01
影响因子：
3.4
通讯作者：
Ho, HN
中科院分区：
文献类型：
--
作者：
Chiou, SH;Sheu, BC;Ho, HN
肿瘤浸润淋巴细胞（til）是宿主免疫系统识别和防御恶性细胞的表现。tll从字面上定义为“肿瘤浸润淋巴细胞”，其后方位于肿瘤组织内。虽然可以找到这样的细胞，但它们不能控制肿瘤的生长。许多人提出了TILs功能障碍的多种机制，包括免疫监视癌症的作用。然而，只有少数癌症类型，如黑色素瘤，通过激活这些细胞进行免疫治疗带来了好处。TILs的功能缺陷与信号分子异常有关；然而，有相互矛盾的数据。tll的死亡归因于癌源性FasL、PD-1和RCAS1的表达。和癌症激活诱导的细胞死亡（AICD）。通过使用tll和动物模型的研究证实，肿瘤特异性免疫反应的妥协被认为不仅是克隆能量机制的结果，而且是耗尽和/或缺失的结果。此外，功能性细胞毒性CD8(+) TILs可能因癌症诱导的抑制性NK受体上调或近端信号异常而失效。此外，免疫特权部分归因于调节性T细胞募集到肿瘤部位。处于T细胞功能中心的IL-2信号的失效与癌症来源的基质金属蛋白酶（MMPs）的酶活性有关。最后，癌细胞利用IDO表达（妊娠相关免疫抑制的重要酶）可能在肿瘤免疫中发挥作用。癌症类型、起源、发育阶段和个体遗传背景的差异可能解释了差异，甚至矛盾，这可能是免疫疗法仅对少数癌症类型有效的原因。描述TILs功能缺陷背后的机制不仅有助于提高成功治愈的机会，而且有助于理解免疫系统在面对恶性肿瘤时尚未完全确定的作用。2005爱思唯尔爱尔兰有限公司版权所有。
Tumor-infiltrating lymphocytes (TILs) develop as manifestations of the recognition and defense against malignant cells by the host immune system. TlLs were literally defined as "tumor-infiltrating lymphocytes", which a posteriori locate within the tumor tissues. Although such cells can be found, they fail to control the growth of tumor. Many have proposed diverse mechanisms for dysfunction of TILs with regard to the roles of immunosurveillance against cancer. However, only a few cancer types, e.g. melanoma, have seen the benefits brought by activating these cells for immunotherapy. Functional defects of TILs have been linked to abnormalities of signaling molecules; however, there is conflicting data. The death of TlLs was attributed to expression of cancer-derived FasL, PD-1 and RCAS1. and cancer-induced activation-induced cell death (AICD). Confirmed by studies using TlLs and animal models, the compromise of tumor-specific immune responses was thought to result from not only mechanisms of clonal anergy but also exhaustion and/or deletion. Furthermore, functional cytotoxic CD8(+) TILs might be rendered incompetent by cancer-induced up-regulation of inhibitory NK receptors or proximal signaling abnormalities. Additionally, immune privilege was partly attributed to recruitment of regulatory T cells to the tumor sites. The failure of IL-2 signaling, which stands at the center of T cell functionalities, had been linked to the enzymatic activity of cancer-derived matrix metalloproteinases (MMPs). Finally, the exploitation of IDO expression, an important enzyme in pregnancy-related immunosuppression, by cancer cells might play a role in tumor immunity. The disparity of cancer types, origin, developmental stages and individual genetic backgrounds likely account for differences, or even contradictions, which might be the reason why immunotherapy works only on a few cancer types. Delineating the mechanisms behind functional defects of TILs can help not only boost chances of the development of a successful cure but understand the not fully identified roles played by immune system in the face of malignancies. (c) 2005 Elsevier Ireland Ltd. All rights reserved.