Increased diversity with reduced "diversity evenness" of tumor infiltrating T-cells for the successful cancer immunotherapy.
Increased diversity with reduced "diversity evenness" of tumor infiltrating T-cells for the successful cancer immunotherapy.
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肿瘤浸润T细胞的“多样性均匀度”增加了多样性，以成功地进行癌症免疫疗法。
DOI：
10.1038/s41598-018-19548-y
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发表时间：
2018-01-18
影响因子：
4.6
通讯作者：
Kakimi K
中科院分区：
文献类型：
--
作者：
Hosoi A;Takeda K;Nagaoka K;Iino T;Matsushita H;Ueha S;Aoki S;Matsushima K;Kubo M;Morikawa T;Kitaura K;Suzuki R;Kakimi K
为了优化缺乏免疫相关不良事件的癌症免疫治疗，我们对B16黑色素瘤小鼠接受抗pd -1、抗ctla -4、抗4-1BB、抗cd4或抗pd -1和4-1BB联合抗体的肿瘤浸润CD8+ t细胞进行了TCR库分析。虽然肿瘤中的CD8+ t细胞被这些疗法或多或少地激活和扩增，但只有抗pd -1、抗pd -1/4- 1bb联合或抗cd4治疗才能实现肿瘤生长抑制，而抗ctla -4或抗4- 1bb单药治疗无法实现。CD8+ T细胞效应功能和TCR多样性的增加以及肿瘤中某些TCR克隆型的富集与抗肿瘤作用有关。相反，外周t细胞的多克隆活化与组织损伤有关。因此，最佳的联合治疗通过延长选择性CD8+ t细胞在肿瘤中的特异性激活而不是在周围的激活来增加TCR多样性。提出了在TCR多样性中引入均匀度的概念。
To facilitate the optimization of cancer immunotherapy lacking immune-related adverse events, we performed TCR repertoire analysis of tumor-infiltrating CD8+ T-cells in B16 melanoma-bearing mice receiving anti-PD-1, anti-CTLA-4, anti-4-1BB, anti-CD4 or a combination of anti-PD-1 and 4-1BB antibodies. Although CD8+ T-cells in the tumor were activated and expanded to a greater or lesser extent by these therapies, tumor growth suppression was achieved only by anti-PD-1, anti-PD-1/4-1BB combined, or by anti-CD4 treatment, but not by anti-CTLA-4 or anti-4-1BB monotherapy. Increased CD8+ T cell effector function and TCR diversity with enrichment of certain TCR clonotypes in the tumor was associated with anti-tumor effects. In contrast, polyclonal activation of T-cells in the periphery was associated with tissue damage. Thus, optimal combination therapy increases TCR diversity with extended activation of selective CD8+ T-cells specifically in the tumor but not in the periphery. Incorporation of the concept of evenness for the TCR diversity is proposed.
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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：
10.1038/nrc3239
发表时间：
2012-03-22
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Pardoll DM
通讯作者：
Pardoll DM
DOI：
10.1158/1078-0432.ccr-13-2648
发表时间：
2014-05-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Robert L;Tsoi J;Wang X;Emerson R;Homet B;Chodon T;Mok S;Huang RR;Cochran AJ;Comin-Anduix B;Koya RC;Graeber TG;Robins H;Ribas A
通讯作者：
Ribas A
一种新的高通量测序方法，用于确定T细胞受体（TCR）α和β曲目的多样性和相似性，并确定潜在的新不变TCRα链。
影响因子：
3
作者：
Kitaura K;Shini T;Matsutani T;Suzuki R
通讯作者：
Suzuki R
影响因子：
64.5
作者：
Riaz N;Havel JJ;Makarov V;Desrichard A;Urba WJ;Sims JS;Hodi FS;Martín-Algarra S;Mandal R;Sharfman WH;Bhatia S;Hwu WJ;Gajewski TF;Slingluff CL Jr;Chowell D;Kendall SM;Chang H;Shah R;Kuo F;Morris LGT;Sidhom JW;Schneck JP;Horak CE;Weinhold N;Chan TA
通讯作者：
Chan TA