Tumor-infiltrating regulatory T cells inhibit endogenous cytotoxic T cell responses to lung adenocarcinoma.
Tumor-infiltrating regulatory T cells inhibit endogenous cytotoxic T cell responses to lung adenocarcinoma.
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肿瘤浸润的调节性T细胞抑制内源性细胞毒性T细胞对肺腺癌的反应。
DOI：
10.4049/jimmunol.1301317
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发表时间：
2013-08-15
期刊：
影响因子：
--
通讯作者：
Coussens LM
中科院分区：
文献类型：
--
作者：
Ganesan AP;Johansson M;Ruffell B;Yagui-Beltrán A;Lau J;Jablons DM;Coussens LM
免疫细胞在人类非小细胞肺癌（NSCLC）中占肿瘤质量的很大比例，但这种浸润的确切组成和意义尚不清楚。在此，我们检测了人NSCLC以及在CC 10-TAg转基因小鼠中发展的NSCLC的免疫复杂性，并揭示了CD 4 + T淋巴细胞代表了CD 45+免疫细胞的优势群体，并且相对于正常肺组织，CD 4 + FoxP 3+调节性T细胞（TcR）作为总CD 4+细胞的比例显著增加。为了评估增加的Treg细胞的功能意义，我们评估了CD 8 + T细胞缺陷/CC 10-TAg小鼠，并揭示了CD 8 + T细胞显著控制肿瘤生长，其抗肿瘤活性被Treg细胞部分抑制。然而，虽然抗CD 25耗竭mAb作为单一疗法优先耗竭TcB并改善早期肿瘤发展期间CD 8 + T细胞介导的肿瘤进展控制，但类似的单一疗法在后期阶段无效。由于用抗CD 25 mAb治疗的早期NSCLC小鼠表现出与表达升高水平的颗粒酶A、颗粒酶B、穿孔素和干扰素-γ的CD 8 + T细胞浸润相关的肿瘤细胞死亡增加，因此我们评价了卡铂联合治疗，其导致的生存期显著延长，超过了单独化疗的观察结果，表明Treg耗竭联合细胞毒性疗法作为晚期NSCLC的治疗策略可能是有益的。
Immune cells comprise a substantial proportion of the tumor mass in human non-small cell lung cancers (NSCLC), but the precise composition and significance of this infiltration is unclear. Herein we examined immune complexity of human NSCLC as well as NSCLC developing in CC10-TAg transgenic mice, and revealed that CD4+ T lymphocytes represent the dominant population of CD45+ immune cells, and relative to normal lung tissue, CD4+FoxP3+ regulatory T cells (Tregs) were significantly increased as a proportion of total CD4+ cells. To assess the functional significance of increased Treg cells, we evaluated CD8+ T cell-deficient/CC10-TAg mice and revealed that CD8+ T cells significantly controlled tumor growth with anti-tumor activity that was partially repressed by Treg cells. However, while treatment with anti-CD25 depleting mAb as monotherapy preferentially depleted Tregs and improved CD8+ T cell-mediated control of tumor progression during early tumor development, similar monotherapy was ineffective at later stages. Since mice bearing early NSCLC treated with anti-CD25 mAb exhibited increased tumor cell death associated with infiltration by CD8+ T cells expressing elevated levels of granzyme A, granzyme B, perforin and interferon-γ, we therefore evaluated carboplatin combination therapy resulting in a significantly extended survival beyond that observed with chemotherapy alone, indicating that Treg depletion in combination with cytotoxic therapy may be beneficial as a treatment strategy for advanced NSCLC.
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影响因子：
11.2
作者：
Deeb, Kristin K.;Michalowska, Aleksandra M.;Green, Jeffrey E.
通讯作者：
Green, Jeffrey E.
DOI：
10.4049/jimmunol.0903009
发表时间：
2010-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
DiLillo DJ;Yanaba K;Tedder TF
通讯作者：
Tedder TF
影响因子：
13.6
作者：
Mahajan, Deepika;Wang, Yiping;Harris, David C. H.
通讯作者：
Harris, David C. H.
影响因子：
5.3
作者：
Johnson, SK;Kerr, KM;Jeffrey, RR
通讯作者：
Jeffrey, RR
CD4+ CD25+调节性T细胞以转化的生长因子β依赖性方式抑制天然杀伤细胞的功能。
影响因子：
15.3
作者：
Ghiringhelli, F;Ménard, C;Terme, M;Flament, C;Taieb, J;Chaput, N;Puig, PE;Novault, S;Escudier, B;Vivier, E;Lecesne, A;Robert, C;Blay, JY;Bernard, J;Caillat-Zucman, S;Freitas, A;Tursz, T;Wagner-Ballon, O;Capron, C;Vainchencker, W;Martin, F;Zitvogel, L
通讯作者：
Zitvogel, L