Data from Predictive and Dynamic Signature for Antiangiogenics in Combination with a PD1 Inhibitor in Soft-Tissue Sarcoma: Correlative Studies Linked to the IMMUNOSARC Trial

相关 签名(拓扑) 软组织肉瘤 肉瘤 软组织 医学 肿瘤科 内科学 计算机科学 病理 数学 几何学 语言学 哲学
作者
David S. Moura,Jesús M. López Martí,Iva Benešová,Carlos E. de Andrea,Davide di Lernia,Serena Lacerenza,José L. Mondaza-Hernández,Marta Martín‐Ruiz,Marta Ramírez-Calvo,Giovanni Grignani,Javier Martínez‐Trufero,Andrés Redondo,Claudia Valverde,Silvia Stacchiotti,Antonio López‐Pousa,José Antonio López‐Guerrero,Antonio Gutiérrez,Victor Encinas-Tobajas,Nadia Hindi,Dario Sangiolo,José A. López-Martín,Zuzana Střížová,Javier Martín‐Broto
标识
DOI:10.1158/1078-0432.c.7541193
摘要

<div>Purpose:<p>The IMMUNOSARC trial combined an antiangiogenic agent (sunitinib) with a PD1 inhibitor (nivolumab) in advanced sarcomas. Here, we present the first correlative studies of the soft-tissue sarcoma cohort enrolled in this trial.</p>Experimental Design:<p>Formalin-fixed paraffin-embedded and peripheral blood samples were collected at baseline and week 13. Formalin-fixed paraffin-embedded samples were used for transcriptomics and multiplex immunofluorescence, whereas peripheral blood samples were used for multiplexed immunoassays. Flow cytometry and Luminex assays were performed to validate translational findings in tumor-isolated cells and peripheral blood mononuclear cells derived from patients.</p>Results:<p>The density of intratumoral CD8<sup>+</sup> T cells, measured by multiplexed immunophenotyping, was significantly increased after treatment. This augment was accompanied by the dynamic significant increase in the gene expressions of <i>CD86</i>, <i>CHI3L1</i>, <i>CXCL10</i>, <i>CXCL9</i>, <i>LAG3</i>, and <i>VCAM1</i> and the decrease in the expression levels of <i>NR4A1</i>. In peripheral blood, 12 proteins were significantly modulated by treatment at week 13. A score integrating the dynamic expression of the 7 genes and the 12 soluble factors separated 2 groups with distinct progression-free survival (PFS): 4.1 months [95% confidence interval, 3.5–not reached (NR)] versus 17 months (95% confidence interval, 12.0–NR), <i>P</i> = 0.014. This molecular score was predictive of PFS when applied to the normalized data determined in the baseline samples.</p>Conclusions:<p>Treatment with sunitinib and nivolumab inflamed the sarcoma microenvironment, increasing CD8<sup>+</sup> T-cell density and the expression of several genes/proteins with relevance in the response to PD1 inhibitors. A molecular signature identified two groups of patients with distinct PFS for the combination of antiangiogenics plus PD1 inhibitor therapy.</p></div>
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
728完成签到,获得积分10
3秒前
xiaofeng5838完成签到,获得积分10
3秒前
ronnie完成签到,获得积分10
3秒前
6秒前
寒冷芷蕊完成签到,获得积分20
6秒前
6秒前
Jane完成签到,获得积分10
6秒前
一氧化二氢完成签到,获得积分10
12秒前
凡事发生必有利于我完成签到,获得积分10
13秒前
yihaiqin完成签到 ,获得积分10
17秒前
轩辕剑身完成签到,获得积分0
17秒前
coolkid完成签到 ,获得积分0
18秒前
你怎么那么美完成签到,获得积分10
18秒前
游艺完成签到 ,获得积分10
21秒前
冬月完成签到 ,获得积分10
21秒前
薛乎虚完成签到 ,获得积分10
22秒前
23秒前
大胖完成签到,获得积分10
23秒前
野火197完成签到,获得积分10
27秒前
28秒前
量子星尘发布了新的文献求助10
31秒前
April完成签到,获得积分10
31秒前
周舟完成签到 ,获得积分10
34秒前
V_I_G完成签到 ,获得积分10
35秒前
nick完成签到,获得积分10
36秒前
高高高完成签到 ,获得积分10
39秒前
彪壮的亦瑶完成签到 ,获得积分10
40秒前
科研通AI2S应助科研通管家采纳,获得10
42秒前
Perry应助科研通管家采纳,获得60
42秒前
Akim应助科研通管家采纳,获得10
42秒前
鱼雷完成签到,获得积分10
43秒前
廿伊发布了新的文献求助10
45秒前
我是125完成签到,获得积分10
47秒前
依人如梦完成签到 ,获得积分10
48秒前
49秒前
PDIF-CN2完成签到,获得积分10
53秒前
雪雪完成签到 ,获得积分10
54秒前
55秒前
Willow完成签到,获得积分10
58秒前
研研研完成签到,获得积分10
59秒前
高分求助中
【提示信息,请勿应助】关于scihub 10000
Les Mantodea de Guyane: Insecta, Polyneoptera [The Mantids of French Guiana] 3000
徐淮辽南地区新元古代叠层石及生物地层 3000
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
Handbook of Industrial Diamonds.Vol2 1100
Global Eyelash Assessment scale (GEA) 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 550
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 4038157
求助须知:如何正确求助?哪些是违规求助? 3575869
关于积分的说明 11373842
捐赠科研通 3305650
什么是DOI,文献DOI怎么找? 1819255
邀请新用户注册赠送积分活动 892655
科研通“疑难数据库(出版商)”最低求助积分说明 815022