Induction of tumoricidal function in CD4+ T cells is associated with concomitant memory and terminally differentiated phenotype.
Induction of tumoricidal function in CD4+ T cells is associated with concomitant memory and terminally differentiated phenotype.
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DOI：
10.1084/jem.20120532
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发表时间：
2012-10-22
期刊：
影响因子：
--
通讯作者：
Wolchok JD
中科院分区：
文献类型：
--
作者：
Hirschhorn-Cymerman D;Budhu S;Kitano S;Liu C;Zhao F;Zhong H;Lesokhin AM;Avogadri-Connors F;Yuan J;Li Y;Houghton AN;Merghoub T;Wolchok JD
0X 40接合诱导细胞毒性CD 4 + T细胞亚群以根除晚期黑素瘤利用适应性免疫应答治疗恶性肿瘤现在是临床现实。有几种策略用于治疗黑色素瘤;然而，很少有完全反应的结果。CD 4 + T细胞是抗肿瘤免疫的重要和有效的介质，并且特异性CD 4 + T细胞的过继转移可以促进小鼠和患者中的肿瘤消退。OX 40是一种主要在活化的CD 4 + T细胞上表达的共刺激分子，可促进和增强抗肿瘤免疫力，但在小鼠的大肿瘤上的成功有限。我们表明，OX 40的参与，在化疗诱导的淋巴细胞减少症的背景下，诱导一种新的CD 4 + T细胞群体的特征在于表达的主调节eomesodermin，导致终端分化和中央记忆表型，伴随分泌的Th 1和Th 2细胞因子。这种CD 4 + T细胞亚群根除了小鼠中非常晚期的黑素瘤，并且类似的人类肿瘤特异性CD 4 + T细胞群体可以在体外系统中杀死黑素瘤。该疗法的效力扩展到支持抗原丢失变体的旁观者杀伤效应。我们的研究结果表明，这些独特的编程效应CD 4 + T细胞具有独特的表型，具有增加的杀肿瘤能力，并支持使用免疫调节重编程的CD 4 + T细胞的表型。
OX40 engagement induces a cytotoxic CD4+ T cell subpopulation to eradicate advance melanomas Harnessing the adaptive immune response to treat malignancy is now a clinical reality. Several strategies are used to treat melanoma; however, very few result in a complete response. CD4+ T cells are important and potent mediators of anti-tumor immunity and adoptive transfer of specific CD4+ T cells can promote tumor regression in mice and patients. OX40, a costimulatory molecule expressed primarily on activated CD4+ T cells, promotes and enhances anti-tumor immunity with limited success on large tumors in mice. We show that OX40 engagement, in the context of chemotherapy-induced lymphopenia, induces a novel CD4+ T cell population characterized by the expression of the master regulator eomesodermin that leads to both terminal differentiation and central memory phenotype, with concomitant secretion of Th1 and Th2 cytokines. This subpopulation of CD4+ T cells eradicates very advanced melanomas in mice, and an analogous population of human tumor-specific CD4+ T cells can kill melanoma in an in vitro system. The potency of the therapy extends to support a bystander killing effect of antigen loss variants. Our results show that these uniquely programmed effector CD4+ T cells have a distinctive phenotype with increased tumoricidal capability and support the use of immune modulation in reprogramming the phenotype of CD4+ T cells.
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DOI：
10.1056/nejmoa1003466
发表时间：
2010-08-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
Hodi FS;O'Day SJ;McDermott DF;Weber RW;Sosman JA;Haanen JB;Gonzalez R;Robert C;Schadendorf D;Hassel JC;Akerley W;van den Eertwegh AJ;Lutzky J;Lorigan P;Vaubel JM;Linette GP;Hogg D;Ottensmeier CH;Lebbé C;Peschel C;Quirt I;Clark JI;Wolchok JD;Weber JS;Tian J;Yellin MJ;Nichol GM;Hoos A;Urba WJ
通讯作者：
Urba WJ
DOI：
10.1084/jem.20082205
发表时间：
2009-05-11
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hirschhorn-Cymerman D;Rizzuto GA;Merghoub T;Cohen AD;Avogadri F;Lesokhin AM;Weinberg AD;Wolchok JD;Houghton AN
通讯作者：
Houghton AN
影响因子：
32.4
作者：
Hegazy, Ahmed N.;Peine, Michael;Loehning, Max
通讯作者：
Loehning, Max
影响因子：
158.5
作者：
Hunder, Naomi N.;Wallen, Herschel;Yee, Cassian
通讯作者：
Yee, Cassian
DOI：
10.1084/jem.20091279
发表时间：
2010-01-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Budhu S;Loike JD;Pandolfi A;Han S;Catalano G;Constantinescu A;Clynes R;Silverstein SC
通讯作者：
Silverstein SC