Chimeric NKG2D T cells require both T cell- and host-derived cytokine secretion and perforin expression to increase tumor antigen presentation and systemic immunity.
Chimeric NKG2D T cells require both T cell- and host-derived cytokine secretion and perforin expression to increase tumor antigen presentation and systemic immunity.
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DOI：
10.4049/jimmunol.0900721
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发表时间：
2009-08-15
期刊：
影响因子：
--
通讯作者：
Sentman CL
中科院分区：
文献类型：
--
作者：
Barber A;Sentman CL
用表达嵌合 NKG2D 受体 (chNKG2D) 的 T 细胞治疗患有卵巢肿瘤的小鼠，会产生针对肿瘤抗原的保护性宿主免疫反应。在这项研究中，确定了 chNKG2D T 细胞诱导宿主针对卵巢肿瘤免疫所需的机制，以及哪些宿主免疫细胞参与肿瘤消除。 chNKG2D T 细胞治疗导致脾脏和肿瘤部位的宿主 NK、CD4+ 和 CD8+ T 细胞产生持续增加的 IFNγ，并且这种情况在 T 细胞注射后持续数周。在 chNKG2D T 细胞治疗的小鼠中，肿瘤抗原呈递增强，并且在用 chNKG2D T 细胞治疗后，肿瘤部位和引流淋巴结中存在更多数量的肿瘤特异性 T 细胞。宿主细胞细胞因子分泌和抗原呈递的增加依赖于 chNKG2D T 细胞来源的穿孔素、IFNγ 和 GM-CSF。宿主免疫机制参与肿瘤消除，因为在缺乏穿孔素、IFNγ、NK 细胞或 T 和 B 细胞 (Rag1−/−) 的小鼠中，肿瘤生长的抑制有限。宿主来源的 GM-CSF 或 CD1 依赖性 NKT 细胞没有任何作用，因为缺乏这些细胞的小鼠能够像接受治疗的野生型 B6 小鼠一样清除肿瘤。总之，chNKG2D T细胞需要细胞毒性和细胞因子分泌，以及宿主免疫细胞的参与才能产生宿主抗肿瘤免疫反应并发挥完全功效。
Treatment of mice bearing established ovarian tumors with T cells expressing chimeric NKG2D receptors (chNKG2D) develop protective host immune responses to tumor antigens. In this study, the mechanisms that chNKG2D T cells require to induce host immunity against ovarian tumors and which of the host immune cells are involved in tumor elimination were determined. Treatment with chNKG2D T cells led to a sustained, increased IFNγ production by host NK, CD4+, and CD8+ T cells in the spleen and at the tumor site and this continued for many weeks after T cell injection. Tumor antigen presentation was enhanced in chNKG2D T cell treated mice, and there were greater numbers of tumor-specific T cells at the tumor site and in draining lymph nodes after treatment with chNKG2D T cells. The increase in host cell cytokine secretion and antigen presentation was dependent on chNKG2D T cell-derived perforin, IFNγ, and GM-CSF. Host immune mechanisms were involved in tumor elimination because inhibition of tumor growth was limited in mice that lacked perforin, IFNγ, NK cells, or T and B cells (Rag1−/−). There was no role for host-derived GM-CSF or CD1-dependent NKT cells, as mice deficient in these were able to clear tumors as well as treated wildtype B6 mice. In summary, chNKG2D T cells required both cytotoxicity and cytokine secretion as well as the participation of host immune cells for development of a host anti-tumor immune response and complete efficacy.
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通过淋巴结消除来清除稳态细胞因子下沉，增强了采用转移的肿瘤特异性CD8+ T细胞的功效。
影响因子：
15.3
作者：
Gattinoni, Luca;Finkelstein, Steven E;Klebanoff, Christopher A;Antony, Paul A;Palmer, Douglas C;Spiess, Paul J;Hwang, Leroy N;Yu, Zhiya;Wrzesinski, Claudia;Heimann, David M;Surh, Charles D;Rosenberg, Steven A;Restifo, Nicholas P
通讯作者：
Restifo, Nicholas P
影响因子：
4.4
作者：
Barber, Amorette;Zhang, Tong;Sentman, Charles L.
通讯作者：
Sentman, Charles L.
影响因子：
4.4
作者：
Barber, Melissa A.;Zhang, Tong;Sentman, Charles L.
通讯作者：
Sentman, Charles L.
影响因子：
11.2
作者：
Huang, B;Zhao, J;Xiong, HB
通讯作者：
Xiong, HB
影响因子：
3.7
作者：
Grundy, Martin A.;Sentman, Charles L.
通讯作者：
Sentman, Charles L.