Bystander killing of cancer requires the cooperation of CD4(+) and CD8(+) T cells during the effector phase.
Bystander killing of cancer requires the cooperation of CD4(+) and CD8(+) T cells during the effector phase.
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DOI：
10.1084/jem.20092450
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发表时间：
2010-10-25
期刊：
影响因子：
--
通讯作者：
Schreiber H
中科院分区：
文献类型：
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作者：
Schietinger A;Philip M;Liu RB;Schreiber K;Schreiber H
非恶性间质的杀伤需要在肿瘤微环境中的效应期期间CD4+和CD8+ T细胞之间的合作。癌症通常通过肿瘤抗原和抗原呈递主要组织相容性复合物分子的丢失或下调来逃避细胞毒性T淋巴细胞介导的破坏。因此，我们已经集中我们的努力，免疫策略，破坏癌细胞的生存和生长所必需的非恶性基质细胞。在这项研究中，我们开发了一种非T细胞受体转基因的免疫活性肿瘤模型，以确定荷瘤宿主自身的免疫系统是否可以通过基质靶向消除癌细胞，以及CD4+ T细胞在此过程中与CD8+ T细胞一起发挥什么作用。我们发现，侵袭性癌症可以通过靶向肿瘤间质的T细胞来根除。然而，成功的消除需要CD4+和CD8+ T细胞的合作，不仅在诱导阶段，而且在效应阶段的肿瘤微环境，这意味着一个新的作用，为CD4+ T细胞，以前没有描述。我们的研究证明了基质靶向作为癌症免疫疗法的潜力，并表明成功的抗癌策略必须在正确的时间和正确的地点促进CD4+和CD8+ T细胞之间的合作。
Killing of nonmalignant stroma requires cooperation between CD4+ and CD8+ T cells during the effector phase in the tumor microenvironment. Cancers frequently evade cytotoxic T lymphocyte–mediated destruction through loss or down-regulation of tumor antigens and antigen-presenting major histocompatibility complex molecules. Therefore, we have concentrated our efforts on immunological strategies that destroy nonmalignant stromal cells essential for the survival and growth of cancer cells. In this study, we developed a non–T cell receptor transgenic, immunocompetent tumor model to determine whether tumor-bearing hosts’ own immune systems could eliminate cancer cells through stromal targeting and what role CD4+ T cells play alongside CD8+ T cells in this process. We found that aggressive cancers could be eradicated by T cell targeting of tumor stroma. However, successful elimination required the cooperation of CD4+ and CD8+ T cells not only during the induction phase but also during the effector phase in the tumor microenvironment, implying a new role for CD4+ T cells that has not been previously described. Our study demonstrates the potential of stromal targeting as a cancer immunotherapy and suggests that successful anticancer strategies must facilitate cooperation between CD4+ and CD8+ T cells at the right times and the right places.