Antigen loss and tumor-mediated immunosuppression facilitate tumor recurrence.
Antigen loss and tumor-mediated immunosuppression facilitate tumor recurrence.
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DOI：
10.1586/erv.12.107
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发表时间：
2012-11
影响因子：
6.2
通讯作者：
McNeel DG
中科院分区：
文献类型：
--
作者：
Olson BM;McNeel DG
虽然近年来肿瘤免疫治疗取得了显著的成功，但肿瘤用来逃避免疫反应的机制为最大限度地发挥临床效益提供了巨大的障碍。逃逸机制，如抗原丢失，MHC表达减少，以及肿瘤介导的抗肿瘤免疫反应的抑制作用，可以导致最有效的抗肿瘤免疫反应在肿瘤部位变得无能为力。在这项研究中，作者表明，过继转移肿瘤抗原特异性的CD4+和CD8+T细胞与肿瘤细胞免疫相结合，可以在淋巴细胞减少的动物中诱导已建立的皮下肿瘤的消退，但不能诱导淋巴充足的动物皮下肿瘤的消退。然而，使用次佳剂量的转移细胞，然后接种疫苗，作者确定了抗原表达减少的复发肿瘤的发展。在接受类似治疗的动物身上，这些肿瘤仍然可以被根除；然而，他们发现，从复发肿瘤动物身上转移的CD4+T细胞获得了抑制表型。这项工作突出了了解肿瘤逃逸机制的重要性，特别是强调了肿瘤在调节抗原特异性免疫反应中的作用，以及寻找机制以避免开发可存活的逃逸变体的关键重要性。
While tumor immunotherapy has seen notable success in recent years, mechanisms that tumors utilize to escape immune responses have provided significant hurdles to maximal clinical benefit. Escape mechanisms such as antigen loss, decreased MHC expression, as well as tumor-mediated suppressive effects on antitumor immune responses, can cause the most potent antitumor immune response to be rendered powerless at the tumor site. In this study, the authors show that the adoptive transfer of tumor antigen-specific CD4+ and CD8+ T cells combined with tumor cell immunization can elicit regression of established subcutaneous tumors in lymphopenic, but not lymphoreplete, animals. However, using a suboptimal dose of transferred cells followed by vaccination, the authors identify the development of recurrent tumors with reduced antigen expression. These tumors could still be eradicated in similarly treated animals; however, they found that transferred CD4+ T cells from animals with recurrent tumors acquired a suppressive phenotype. This work highlights the importance of understanding mechanisms of tumor escape, particularly underscoring the role of the tumor in modulating antigen-specific immune responses, and the critical importance of finding mechanisms to avoid the development of viable escape variants.
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影响因子：
64.8
作者：
Shankaran, V;Ikeda, H;Schreiber, RD
通讯作者：
Schreiber, RD
影响因子：
64.8
作者：
DuPage, Michel;Mazumdar, Claire;Schmidt, Leah M.;Cheung, Ann F.;Jacks, Tyler
通讯作者：
Jacks, Tyler
影响因子：
15.3
作者：
Zhou, G;Lu, ZB;McCadden, JD;Levitsky, HI;Marson, AL
通讯作者：
Marson, AL
影响因子：
56.9
作者：
Dudley, ME;Wunderlich, JR;Rosenberg, SA
通讯作者：
Rosenberg, SA
影响因子：
4.4
作者：
Jensen, Shawn M.;Twitty, Christopher G.;Fox, Bernard A.
通讯作者：
Fox, Bernard A.