Platelets stimulate programmed death-ligand 1 expression by cancer cells: Inhibition by anti-platelet drugs.

血小板活化 药理学 细胞凋亡 细胞生物学 医学
作者
Amir Asgari,Gabriela Lesyk,Erika Poitras,Natasha Govindasamy,Kara Terry,Rachel To,Valentina Back,Jan K. Rudzinski,John D. Lewis,Paul Jurasz
出处
期刊:Journal of Thrombosis and Haemostasis [Wiley]
卷期号:19 (11): 2862-2872
标识
DOI:10.1111/jth.15478
摘要

Background Platelets facilitate hematogenous metastasis in part by promoting cancer cell immunoevasion, although our understanding of platelet function in modulating the adaptive immune system in cancer is limited. A major negative regulator of the adaptive response is the immune checkpoint protein Programmed Death Ligand 1 (PD-L1). Objectives As platelets secrete factors that may increase PD-L1 expression, we investigated whether they up-regulate cancer cell PD-L1, thus promoting immunoevasion, and whether common anti-platelet drugs inhibit this process. Methods Platelets were isolated from human volunteers. A549 lung, PD-L1 null A549, and 786-O renal cancer cells were incubated with and without platelets, and cancer cell PD-L1 expression was measured by qPCR and flow cytometry. Additionally, platelet-cancer cell incubations were performed in the presence of common anti-platelet drugs, and with growth factor neutralizing antibodies. Following incubation with platelets, A549 were co-cultured with T-cells and interleukin-2 (IL-2) levels were measured by flow cytometry as a marker of T-cell activation. Results Platelets increased PD-L1 mRNA and surface protein expression by A549 and 786-0 cells. Combined neutralization of VEGF and PDGF prevented the platelet-induced up-regulation of PD-L1 by A549, as did the anti-platelet drug eptifibatide. A549 incubated with platelets demonstrated a reduced ability to activate human T-cells, an effect reversed by eptifibatide. Conclusions As platelets promote immunoevasion of the adaptive immune response by increasing cancer cell PD-L1 expression and as anti-platelet drugs prevent this immunoevasive response, the investigation of anti-platelet drugs as adjuvant therapy to immune checkpoint inhibitors may be warranted in the treatment of cancer.
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
大幅提高文件上传限制,最高150M (2024-4-1)

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
xrkxrk完成签到 ,获得积分10
刚刚
zhuzhu完成签到 ,获得积分10
刚刚
2秒前
负数完成签到,获得积分10
5秒前
5秒前
itsserene应助Jessica采纳,获得20
6秒前
研友_LmbRgn完成签到 ,获得积分10
8秒前
英俊的铭应助学分采纳,获得10
10秒前
11秒前
123完成签到 ,获得积分10
11秒前
打打应助红蜻蜓采纳,获得10
11秒前
酷波er应助无辜不言采纳,获得10
13秒前
坚强的傲南应助横A采纳,获得10
13秒前
狂炫AD钙奶完成签到,获得积分10
15秒前
有人应助阿尼亚采纳,获得10
16秒前
pengyyang发布了新的文献求助10
19秒前
妇愁者联盟完成签到,获得积分10
20秒前
小机灵鬼完成签到,获得积分10
20秒前
珊珊发布了新的文献求助10
21秒前
小二郎应助勤奋花瓣采纳,获得10
22秒前
22秒前
24秒前
朴实的若南完成签到,获得积分10
26秒前
cc20231022关注了科研通微信公众号
26秒前
滴滴哒哒完成签到 ,获得积分10
26秒前
超级涔完成签到 ,获得积分10
27秒前
闹一闹吧费曼先生完成签到 ,获得积分10
27秒前
28秒前
30秒前
30秒前
小Q发布了新的文献求助10
31秒前
33秒前
maxinghrr完成签到,获得积分10
33秒前
34秒前
徐先生发布了新的文献求助10
35秒前
xxx发布了新的文献求助10
36秒前
38秒前
勤奋花瓣发布了新的文献求助10
40秒前
Owen应助yn采纳,获得10
40秒前
Cheney完成签到 ,获得积分10
41秒前
高分求助中
The Oxford Handbook of Social Cognition (Second Edition, 2024) 1050
Kinetics of the Esterification Between 2-[(4-hydroxybutoxy)carbonyl] Benzoic Acid with 1,4-Butanediol: Tetrabutyl Orthotitanate as Catalyst 1000
The Young builders of New china : the visit of the delegation of the WFDY to the Chinese People's Republic 1000
юрские динозавры восточного забайкалья 800
English Wealden Fossils 700
Handbook of Qualitative Cross-Cultural Research Methods 600
Chen Hansheng: China’s Last Romantic Revolutionary 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 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 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3140205
求助须知:如何正确求助?哪些是违规求助? 2790982
关于积分的说明 7797336
捐赠科研通 2447358
什么是DOI,文献DOI怎么找? 1301860
科研通“疑难数据库(出版商)”最低求助积分说明 626345
版权声明 601194