Contraction of T cell richness in lung cancer brain metastases.
Contraction of T cell richness in lung cancer brain metastases.
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DOI：
10.1038/s41598-018-20622-8
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发表时间：
2018-02-01
影响因子：
4.6
通讯作者：
Jen J
中科院分区：
文献类型：
--
作者：
Mansfield AS;Ren H;Sutor S;Sarangi V;Nair A;Davila J;Elsbernd LR;Udell JB;Dronca RS;Park S;Markovic SN;Sun Z;Halling KC;Nevala WK;Aubry MC;Dong H;Jen J
对于适应性免疫系统如何对非小细胞肺癌中的克隆进化和肿瘤异质性做出反应知之甚少。我们分析了20例完全切除的非小细胞肺癌原发灶和成对脑转移瘤患者的T细胞受体β互补决定区3。除了肿瘤突变负荷和预测的新抗原之外，我们还表征了成对之间T细胞克隆的丰富度、丰度和重叠。我们发现，与成对的原发性癌症相比，脑转移瘤中独特的T细胞克隆的数量显着收缩。绝大多数T细胞克隆对单个病变是特异性的，并且成对病变之间的T细胞克隆的重叠最小。尽管T细胞克隆数量收缩，脑转移瘤的非同义突变负荷高于原发性病变。我们的研究结果表明，尽管在转移性病变中观察到更高的突变负荷，但原发性肺癌中的T细胞克隆比其配对转移瘤更丰富。这些结果可能对免疫疗法有影响。
Very little is known about how the adaptive immune system responds to clonal evolution and tumor heterogeneity in non-small cell lung cancer. We profiled the T-cell receptor β complementarity determining region 3 in 20 patients with fully resected non-small cell lung cancer primary lesions and paired brain metastases. We characterized the richness, abundance and overlap of T cell clones between pairs, in addition to the tumor mutation burden and predicted neoantigens. We found a significant contraction in the number of unique T cell clones in brain metastases compared to paired primary cancers. The vast majority of T cell clones were specific to a single lesion, and there was minimal overlap in T cell clones between paired lesions. Despite the contraction in the number of T cell clones, brain metastases had higher non-synonymous mutation burdens than primary lesions. Our results suggest that there is greater richness of T cell clones in primary lung cancers than their paired metastases despite the higher mutation burden observed in metastatic lesions. These results may have implications for immunotherapy.
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影响因子：
4.6
作者：
Harris MG;Hulseberg P;Ling C;Karman J;Clarkson BD;Harding JS;Zhang M;Sandor A;Christensen K;Nagy A;Sandor M;Fabry Z
通讯作者：
Fabry Z
DOI：
10.1016/s1470-2045(16)30053-5
发表时间：
2016-07
期刊：
The Lancet. Oncology
影响因子：
--
作者：
Goldberg SB;Gettinger SN;Mahajan A;Chiang AC;Herbst RS;Sznol M;Tsiouris AJ;Cohen J;Vortmeyer A;Jilaveanu L;Yu J;Hegde U;Speaker S;Madura M;Ralabate A;Rivera A;Rowen E;Gerrish H;Yao X;Chiang V;Kluger HM
通讯作者：
Kluger HM
影响因子：
50.5
作者：
Ilie, M.;Long-Mira, E.;Hofman, P.
通讯作者：
Hofman, P.
影响因子：
6.7
作者：
Mansfield, A. S.;Dong, H.
通讯作者：
Dong, H.
影响因子：
30.8
作者：
Li, Bo;Li, Taiwen;Liu, X. Shirley
通讯作者：
Liu, X. Shirley