Tumour radiosensitivity is associated with immune activation in solid tumours.
Tumour radiosensitivity is associated with immune activation in solid tumours.
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DOI：
10.1016/j.ejca.2017.08.001
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发表时间：
2017-10
期刊：
影响因子：
--
通讯作者：
Torres-Roca JF
中科院分区：
文献类型：
--
作者：
Strom T;Harrison LB;Giuliano AR;Schell MJ;Eschrich SA;Berglund A;Fulp W;Thapa R;Coppola D;Kim S;Frakes J;Foekens J;Mulé JJ;Torres-Roca JF
我们的目标是确定肿瘤放射敏感性是否与所有肿瘤类型的免疫系统激活相关（通过两个基因表达特征（GES）测量）。我们通过机构去识别化数据库中的基因表达分析，鉴定了 10,240 个基因组图谱不同的实体原发性肿瘤。分析中包括两个单独的 GES：放射敏感性指数 (RSI) GES（作为放射敏感性衡量标准的 10 基因 GES）和 12 趋化因子 (12-CK) 特征（作为免疫激活衡量标准的 12 基因 GES）。我们在所有肿瘤样本中测试了 RSI 和 12-CK 是否相互关联，并在一项探索性分析中，在一个由 282 例仅接受手术和术后放疗而未进行全身治疗的早期乳腺癌病例组成的特征明确的独立队列中，检验了它们在预测无远处转移生存 (DMFS) 方面的预后意义。 RSI评分越低，肿瘤放射敏感性越高；而12-CK得分越高，免疫激活程度越高。使用≤0.3745的RSI切点，在所有肿瘤样本中，与RSI高肿瘤（-0.17 [-0.82,0.42]；p<0.001）相比，RSI低肿瘤（n=4,291, 41.9%）的中位12-CK GES值（0.54 [范围-0.136,1.095]）显着更高， 表明放射敏感性与免疫激活有关。在对早期乳腺癌病例的探索性分析中，包含患者年龄、RSI 和 12-CK 的多变量模型为 DMFS 提供了强大的复合模型 (p=0.02)，其中 RSI (HR 0.63 [95%CI 0.36,1.09]) 和 12-CK (HR 0.66 [0.41,1.04]) 各自提供了可比较的贡献。通过两个 GES 测量，肿瘤放射敏感性与免疫激活相关。
Our goal was to determine whether tumor radiosensitivity is associated with activation of the immune system across all tumor types as measured by two gene expression signatures (GES). We identified 10,240 genomically profiled distinct solid primary tumors with gene expression analysis available from an institutional de-identified database. Two separate GES were included in the analysis, the radiosensitivity index (RSI) GES (a 10-gene GES as a measure of radiosensitivity), and the 12-chemokine (12-CK) signature (a 12-gene GES as a measure of immune activation). We tested whether the RSI and 12-CK were associated with each other across all tumor samples, and in an exploratory analysis, their prognostic significance in predicting distant metastasis-free survival (DMFS) among a well-characterized, independent cohort of 282 early-stage breast cancer cases treated with surgery and post-operative radiation alone without systemic therapy. The lower the RSI score, the higher the tumor radiosensitivity; whereas, the higher the 12-CK score the higher the immune activation. Using an RSI cut-point of ≤0.3745, RSI-low tumors (n=4,291, 41.9%) had a significantly higher median 12-CK GES value (0.54 [range −0.136,1.095]) compared with RSI-high tumors (−0.17 [−0.82,0.42]; p<0.001) across all tumor samples, indicating that radiosensitivity is associated with immune activation. In an exploratory analysis of early stage breast cancer cases, a multivariable model with patient age, RSI and 12-CK provided a strong composite model for DMFS (p=0.02), with RSI (HR 0.63 [95%CI 0.36,1.09]) and 12-CK (HR 0.66 [0.41,1.04]) each providing comparable contributions. Tumor radiosensitivity is associated with immune activation as measured by two GES.
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DOI：
10.1097/ppo.0b013e318238216e
发表时间：
2011-11
期刊：
Cancer journal (Sudbury, Mass.)
影响因子：
--
作者：
Fenstermacher DA;Wenham RM;Rollison DE;Dalton WS
通讯作者：
Dalton WS
DOI：
10.1158/1078-0432.ccr-09-0265
发表时间：
2009-09-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Dewan MZ;Galloway AE;Kawashima N;Dewyngaert JK;Babb JS;Formenti SC;Demaria S
通讯作者：
Demaria S
影响因子：
3.5
作者：
Crittenden M;Kohrt H;Levy R;Jones J;Camphausen K;Dicker A;Demaria S;Formenti S
通讯作者：
Formenti S
影响因子：
11.5
作者：
Eschrich, Steven A.;Fulp, William J.;Torres-Roca, Javier F.
通讯作者：
Torres-Roca, Javier F.
影响因子：
3.4
作者：
Bernstein, Michael B.;Garnett, Charlie T.;Guha, Chandan
通讯作者：
Guha, Chandan