Plasma IL-6 changes correlate to PD-1 inhibitor responses in NSCLC.
Plasma IL-6 changes correlate to PD-1 inhibitor responses in NSCLC.
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DOI：
10.1136/jitc-2020-000678
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发表时间：
2020-10
影响因子：
10.9
通讯作者：
Walt DR
中科院分区：
文献类型：
--
作者：
Keegan A;Ricciuti B;Garden P;Cohen L;Nishihara R;Adeni A;Paweletz C;Supplee J;Jänne PA;Severgnini M;Awad MM;Walt DR
缺乏基于血液的抗实体瘤免疫检查点阻断（ICB）反应的生物标志物。我们假设，随着程序性细胞死亡蛋白1 （PD-1）途径抑制剂初始剂量的增加，全身细胞因子水平的变化与临床反应相关。新的超灵敏ELISA技术使定量血浆蛋白在亚微克每毫升浓度。我们通过超灵敏单分子阵列检测非小细胞肺癌患者在抗pd -1治疗前和治疗期间的血浆细胞因子。分别采用Kruskall-Wallis检验和Kaplan-Meier图log-rank检验评估与最佳总缓解和无进展生存期（PFS）的关联。白细胞介素6 （IL-6）水平的降低与PFS的改善相关（n=47例患者，中位PFS: 11 vs 4个月，HR 0.45 (95% CI 0.23 ~ 0.89), p=0.04）。IL-6的变化程度在最佳总反应类别之间存在差异（p=0.01），并与C反应蛋白水平的变化相关。我们还探讨了血浆细胞因子水平与免疫相关不良反应的关系，并观察到一些相关性。这项研究表明，成功的ICB在肿瘤微环境外存在系统性的蛋白质组学反应，血浆中IL-6和CRP水平降低。
Blood-based biomarkers of anti-solid tumor immune checkpoint blockade (ICB) response are lacking. We hypothesized that changes in systemic cytokine levels with the initial doses of programmed cell death protein 1 (PD-1) pathway inhibitors would correlate with clinical responses. New ultrasensitive ELISA technology enables quantitation of plasma proteins in sub-picogram-per-milliliter concentrations. We measured plasma cytokines by ultrasensitive single-molecule array assays in patients with non-small-cell lung carcinoma before and during treatment with anti-PD-1 therapy. Association with best overall response and progression-free survival (PFS) was assessed by Kruskall-Wallis test and Kaplan-Meier plots with log-rank test, respectively. A decrease in interleukin 6 (IL-6) levels was associated with improved PFS (n=47 patients, median PFS: 11 vs 4 months, HR 0.45 (95% CI 0.23 to 0.89), p=0.04). The extent of change in IL-6 differed between best overall response categories (p=0.01) and correlated with changes in C reactive protein levels. We also explored plasma cytokine levels in relation to immune-related adverse effects and observed some correlation. This study suggests the presence of a systemic, proteomic reflection of successful ICB outside the tumor microenvironment with plasma decreases in IL-6 and CRP.
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影响因子：
--
作者：
Chen MF;Kuan FC;Yen TC;Lu MS;Lin PY;Chung YH;Chen WC;Lee KD
通讯作者：
Lee KD
影响因子：
28.2
作者：
Chen PL;Roh W;Reuben A;Cooper ZA;Spencer CN;Prieto PA;Miller JP;Bassett RL;Gopalakrishnan V;Wani K;De Macedo MP;Austin-Breneman JL;Jiang H;Chang Q;Reddy SM;Chen WS;Tetzlaff MT;Broaddus RJ;Davies MA;Gershenwald JE;Haydu L;Lazar AJ;Patel SP;Hwu P;Hwu WJ;Diab A;Glitza IC;Woodman SE;Vence LM;Wistuba II;Amaria RN;Kwong LN;Prieto V;Davis RE;Ma W;Overwijk WW;Sharpe AH;Hu J;Futreal PA;Blando J;Sharma P;Allison JP;Chin L;Wargo JA
通讯作者：
Wargo JA
影响因子：
2.8
作者：
Cohen, Limor;Keegan, Alissa;Walt, David R.
通讯作者：
Walt, David R.
影响因子：
4.2
作者：
Wu, Danlu;Milutinovic, Milena Dumont;Walt, David R.
通讯作者：
Walt, David R.
影响因子：
15.9
作者：
Gao, Sizhi Paul;Mark, Kevin G.;Bromberg, Jacqueline F.
通讯作者：
Bromberg, Jacqueline F.