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首页> 外文期刊>Journal of Reproductive Immunology >Current concepts of tumor-infiltrating lymphocytes in human malignancies.
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Current concepts of tumor-infiltrating lymphocytes in human malignancies.

机译：人类恶性肿瘤中肿瘤浸润淋巴细胞的最新概念。

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Tumor-infiltrating lymphocytes (TILs) develop as manifestations of the recognition and defense against malignant cells by the host immune system. TILs 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 TILs was attributed to expression of cancer-derived FasL, PD-1 and RCAS1, and cancer-induced activation-induced cell death (AICD). Confirmed by studies using TILs 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 curebut understand the not fully identified roles played by immune system in the face of malignancies.
机译：肿瘤浸润淋巴细胞（TIL）的发展是宿主免疫系统识别和防御恶性细胞的表现。 TIL被字面上定义为“肿瘤浸润淋巴细胞”，其位于肿瘤组织内。尽管可以找到这种细胞，但它们无法控制肿瘤的生长。关于针对癌症的免疫监视的作用，许多人提出了多种TILs功能障碍的机制。但是，只有少数几种癌症，例如黑色素瘤已经看到了激活这些细胞进行免疫治疗所带来的好处。 TIL的功能缺陷与信号分子的异常有关。但是，存在冲突的数据。 TIL的死亡归因于癌症衍生的FasL，PD-1和RCAS1的表达，以及癌症诱导的激活诱导的细胞死亡（AICD）。通过使用TIL和动物模型的研究证实，肿瘤特异性免疫反应的损害不仅被认为是克隆无反应性机制的原因，也是疲惫和/或缺失的结果。此外，功能性细胞毒性CD8（+）TILs可能会因癌症诱导的抑制性NK受体上调或近端信号异常而变得无能。另外，免疫特权部分归因于调节性T细胞募集到肿瘤部位。位于T细胞功能中心的IL-2信号传导失败与癌症衍生的基质金属蛋白酶（MMP）的酶促活性有关。最后，癌细胞利用IDO表达（一种与妊娠有关的免疫抑制的重要酶）可能在肿瘤免疫中起作用。癌症类型，来源，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几种癌症起作用的原因。描绘TILs功能缺陷背后的机制不仅可以帮助增加成功治愈方法的机会，而且可以了解免疫系统在面对恶性肿瘤时尚未完全确定的作用。

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