TIL therapy broadens the tumor-reactive CD8(+) T cell compartment in melanoma patients.
TIL therapy broadens the tumor-reactive CD8(+) T cell compartment in melanoma patients.
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DOI：
10.4161/onci.18851
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发表时间：
2012-07-01
期刊：
影响因子：
7.2
通讯作者：
Schumacher TN
中科院分区：
文献类型：
--
作者：
Kvistborg P;Shu CJ;Heemskerk B;Fankhauser M;Thrue CA;Toebes M;van Rooij N;Linnemann C;van Buuren MM;Urbanus JH;Beltman JB;Thor Straten P;Li YF;Robbins PF;Besser MJ;Schachter J;Kenter GG;Dudley ME;Rosenberg SA;Haanen JB;Hadrup SR;Schumacher TN
有强有力的证据表明，过继性T细胞转移和T细胞检查点阻断均可导致人黑色素瘤消退。然而，关于这些癌症疗法对肿瘤反应性T细胞区室的影响的数据很少。为了解决这个问题，我们分析了治疗诱导的T细胞对一组145个黑素瘤相关的CD8 + T细胞表位的反应性。使用这种方法，我们证明，从黑色素瘤患者的个体肿瘤浸润淋巴细胞产物包含对共享的黑色素瘤相关抗原的反应性的独特模式，并且这些反应的组合幅度是令人惊讶的低。重要的是，TIL治疗增加了体内肿瘤反应性T细胞区室的宽度，并且治疗后观察到的T细胞反应性几乎可以完全由匹配细胞产物内观察到的反应性来解释。这些结果确立了高通量监测用于分析免疫活性治疗剂的价值，并表明可以通过制备更明确的肿瘤反应性T细胞产物来增强TIL治疗的临床疗效。
There is strong evidence that both adoptive T cell transfer and T cell checkpoint blockade can lead to regression of human melanoma. However, little data are available on the effect of these cancer therapies on the tumor-reactive T cell compartment. To address this issue we have profiled therapy-induced T cell reactivity against a panel of 145 melanoma-associated CD8+ T cell epitopes. Using this approach, we demonstrate that individual tumor-infiltrating lymphocyte cell products from melanoma patients contain unique patterns of reactivity against shared melanoma-associated antigens, and that the combined magnitude of these responses is surprisingly low. Importantly, TIL therapy increases the breadth of the tumor-reactive T cell compartment in vivo, and T cell reactivity observed post-therapy can almost in full be explained by the reactivity observed within the matched cell product. These results establish the value of high-throughput monitoring for the analysis of immuno-active therapeutics and suggest that the clinical efficacy of TIL therapy can be enhanced by the preparation of more defined tumor-reactive T cell products.
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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
影响因子：
11.2
作者：
Corbiere, Veronique;Chapiro, Jacques;Coulie, Pierre G.
通讯作者：
Coulie, Pierre G.
影响因子：
2.9
作者：
Schmitt, Anita;Tonn, Torsten;Schmitt, Michael
通讯作者：
Schmitt, Michael
影响因子：
11.5
作者：
Besser, Michal J.;Shapira-Frommer, Ronnie;Schachter, Jacob
通讯作者：
Schachter, Jacob
影响因子：
45.3
作者：
Robbins, Paul F.;Morgan, Richard A.;Rosenberg, Steven A.
通讯作者：
Rosenberg, Steven A.