CD122+CD8+ Treg suppress vaccine-induced antitumor immune responses in lymphodepleted mice.
CD122+CD8+ Treg suppress vaccine-induced antitumor immune responses in lymphodepleted mice.
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DOI：
10.1002/eji.200839210
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发表时间：
2010-05
影响因子：
5.4
通讯作者：
Hu, Hong-Ming
中科院分区：
文献类型：
--
作者：
Wang, Li-Xin;Li, Yuhuan;Yang, Guojun;Pang, Pui-yi;Haley, Dan;Walker, Edwin B.;Urba, Walter J.;Hu, Hong-Ming
肿瘤特异性T细胞过继转移前的淋巴清除显著提高了过继T细胞治疗晚期黑色素瘤患者的临床疗效，并增加了肿瘤疫苗在动物模型中的治疗效果。淋巴耗竭减少了淋巴细胞之间的竞争，从而为肿瘤特异性T细胞的增强扩增和存活创造了“空间”。在淋巴耗竭的宿主体内，抗原特异的T细胞仍然需要与经历淋巴细胞减少症驱动的增殖的其他淋巴细胞竞争。在这里，我们描述了原始T细胞、Treg细胞和NK细胞经历淋巴细胞减少症驱动的增殖的相对能力。我们发现，经历淋巴细胞减少驱动的增殖的主要群体是CD122+记忆样T细胞群(CD122+CD8+Treg)，这些细胞与抗原驱动的黑色素瘤特异性T细胞的增殖竞争。去除CD122+CD8+Treg可导致肿瘤特异性T细胞的大量扩增和肿瘤功能效应/记忆T细胞的浸润。我们的结果表明，在重组淋巴耗竭小鼠中，CD122+CD8+Treg由淋巴细胞减少驱动的增殖限制了DC疫苗联合过继转移肿瘤特异性T细胞的抗肿瘤效果。
Lymphodeleption prior to adoptive transfer of tumor-specific T cells greatly improves the clinical efficacy of adoptive T-cell therapy for patients with advanced melanoma, and increases the therapeutic efficacy of cancer vaccines in animal models. Lymphodepletion reduces competition between lymphocytes, and thus creates “space” for enhanced expansion and survival of tumor-specific T cells. Within the lymphodepleted host, Ag-specific T cells still need to compete with other lymphocytes that undergo lymphopenia-driven proliferation. Herein, we describe the relative capacity of naïve T cells, Treg, and NK cells to undergo lymphopenia-driven proliferation. We found that the major population that underwent lymphopenia-driven proliferation was the CD122+ memory-like T-cell population (CD122+CD8+ Treg), and these cells competed with Ag-driven proliferation of melanoma-specific T cells. Removal of CD122+CD8+ Treg resulted in a greater expansion of tumor-specific T cells and tumor infiltration of functional effector/memory T cells. Our results demonstrate the lymphopenia-driven proliferation of CD122+CD8+ Treg in reconstituted lymphodepleted mice limited the antitumor efficacy of DC vaccination in conjunction with adoptive transfer of tumor-specific T cells.
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DOI：
10.1084/jem.20021387
发表时间：
2003-02-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Barthlott T;Kassiotis G;Stockinger B
通讯作者：
Stockinger B
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：
32.4
作者：
Min, BK;McHugh, R;Paul, WE
通讯作者：
Paul, WE
影响因子：
5.4
作者：
McNally, JM;Zarozinski, CC;Welsh, RM
通讯作者：
Welsh, RM
DOI：
10.1084/jem.20051409
发表时间：
2005-11-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen Z;Herman AE;Matos M;Mathis D;Benoist C
通讯作者：
Benoist C