Circulating T Cell Subpopulations Correlate With Immune Responses at the Tumor Site and Clinical Response to PD1 Inhibition in Non-Small Cell Lung Cancer.
Circulating T Cell Subpopulations Correlate With Immune Responses at the Tumor Site and Clinical Response to PD1 Inhibition in Non-Small Cell Lung Cancer.
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DOI：
10.3389/fimmu.2018.01613
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发表时间：
2018
影响因子：
7.3
通讯作者：
Nadler SG
中科院分区：
文献类型：
--
作者：
Manjarrez-Orduño N;Menard LC;Kansal S;Fischer P;Kakrecha B;Jiang C;Cunningham M;Greenawalt D;Patel V;Yang M;Golhar R;Carman JA;Lezhnin S;Dai H;Kayne PS;Suchard SJ;Bernstein SH;Nadler SG
靶向PD 1-PDL 1轴的药物已经改变了癌症治疗。影响PD 1-PDL 1抑制剂临床反应的因素包括肿瘤突变负荷、肿瘤免疫浸润和局部PDL 1表达。为了确定在没有检查点阻断的情况下抗肿瘤免疫应答的外周相关性，我们对黑色素瘤和非小细胞肺癌（NSCLC）患者的循环T细胞亚群和匹配的肿瘤基因表达进行了回顾性研究。值得注意的是，肿瘤炎症基因转录增加的黑色素瘤和非小细胞肺癌患者血液中的CD 4+和CD 8+中央记忆T细胞（CM）与效应T细胞（Eff）比率较高。因此，我们评估了第二个NSCLC队列中的CM/Eff T细胞比率。数据显示高CM/Eff T细胞比率与肿瘤PDL 1表达增加相关。此外，在该NSCLC队列中接受纳武单抗的22名患者中，具有高CM/Eff T细胞比率的患者具有更长的无进展生存期（PFS）（中位生存期：91天vs. 215天）。这些研究结果表明，通过提供一个了解免疫系统状态的窗口，外周T细胞亚群可以告知抗肿瘤免疫应答的状态，并确定黑色素瘤和NSCLC中对检查点抑制剂临床应答的潜在血液生物标志物。
Agents targeting the PD1–PDL1 axis have transformed cancer therapy. Factors that influence clinical response to PD1–PDL1 inhibitors include tumor mutational burden, immune infiltration of the tumor, and local PDL1 expression. To identify peripheral correlates of the anti-tumor immune response in the absence of checkpoint blockade, we performed a retrospective study of circulating T cell subpopulations and matched tumor gene expression in melanoma and non-small cell lung cancer (NSCLC) patients. Notably, both melanoma and NSCLC patients whose tumors exhibited increased inflammatory gene transcripts presented high CD4+ and CD8+ central memory T cell (CM) to effector T cell (Eff) ratios in blood. Consequently, we evaluated CM/Eff T cell ratios in a second cohort of NSCLC. The data showed that high CM/Eff T cell ratios correlated with increased tumor PDL1 expression. Furthermore, of the 22 patients within this NSCLC cohort who received nivolumab, those with high CM/Eff T cell ratios, had longer progression-free survival (PFS) (median survival: 91 vs. 215 days). These findings show that by providing a window into the state of the immune system, peripheral T cell subpopulations inform about the state of the anti-tumor immune response and identify potential blood biomarkers of clinical response to checkpoint inhibitors in melanoma and NSCLC.
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影响因子：
15.9
作者：
Berger, Carolina;Jensen, Michael C.;Riddell, Stanley R.
通讯作者：
Riddell, Stanley R.
影响因子：
82.9
作者：
Gros A;Parkhurst MR;Tran E;Pasetto A;Robbins PF;Ilyas S;Prickett TD;Gartner JJ;Crystal JS;Roberts IM;Trebska-McGowan K;Wunderlich JR;Yang JC;Rosenberg SA
通讯作者：
Rosenberg SA
DOI：
10.1073/pnas.0503726102
发表时间：
2005-07-05
影响因子：
11.1
作者：
Klebanoff, CA;Gattinoni, L;Restifo, NP
通讯作者：
Restifo, NP
影响因子：
8
作者：
Yan, Yiyi;Cao, Siyu;Dong, Haidong
通讯作者：
Dong, Haidong
影响因子：
50.5
作者：
Hui, R.;Garon, E. B.;Rizvi, N. A.
通讯作者：
Rizvi, N. A.