M2-polarized and tumor-associated macrophages alter NK cell phenotype and function in a contact-dependent manner

生物 髓源性抑制细胞 癌症研究 细胞毒性 白细胞介素12 细胞 淋巴因子激活杀伤细胞 Janus激酶3 肿瘤微环境 细胞生物学 白细胞介素21 巨噬细胞 免疫学 体外 免疫系统 T细胞 细胞毒性T细胞 癌症 抑制器 生物化学 遗传学
作者
Tamara Krneta,Amy Gillgrass,Sophie M. Poznanski,Marianne V. Chew,Amanda J. Lee,Martin Kolb,Ali A. Ashkar
出处
期刊:Journal of Leukocyte Biology [Oxford University Press]
卷期号:101 (1): 285-295 被引量:92
标识
DOI:10.1189/jlb.3a1215-552r
摘要

Abstract The crosstalk between NK cells and M1 macrophages has a vital role in the protection against infections and tumor development. However, macrophages in the tumor resemble an M2 phenotype, and, at present, their effect on NK cells is less clear. This study investigated whether tumor-associated macrophages (TAMs) have a role in altering NK cell function and phenotype using in vitro cocultures of murine NK cells with peritoneal or bone marrow-derived, M2-polarized macrophages or TAMs isolated from spontaneous mouse breast tumors. We report here that both peritoneal and bone marrow-derived M2 macrophages, as well as TAMs, substantially inhibit NK cell activation and concordant cytotoxicity against tumor cells. The mechanism for this inhibition was found to require contact between the respective cell types. Both M2 macrophages and TAMs are producers of the immunosuppressive cytokine TGF-β. The inhibition of TGF-β restored the cytotoxicity of NK cells in contact with M2 macrophages, implicating TGF-β in the mechanism for NK cell inhibition. In addition to affecting NK cell function, TAMs also induced a CD27lowCD11bhigh-exhausted NK cell phenotype, which corresponds with the reduced activation and cytotoxicity observed. This study reveals a novel implication of TAMs in the tumor-associated inhibition of NK cell function by demonstrating their capacity to directly alter NK cell cytotoxicity and phenotype in a contact-dependent mechanism involving TGF-β. These findings identify the interaction between NK cells and TAMs as a prospective therapeutic target to enhance NK cell effector function for effective NK cell cancer therapies.

科研通智能强力驱动
Strongly Powered by AbleSci AI
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
111222完成签到 ,获得积分20
1秒前
稳重傲柔发布了新的文献求助10
1秒前
科研通AI2S应助张鑫采纳,获得10
1秒前
任性雨筠发布了新的文献求助10
2秒前
科研通AI5应助lezbj99采纳,获得10
2秒前
小许同学完成签到,获得积分10
2秒前
2秒前
4秒前
科研通AI2S应助goldfish采纳,获得30
4秒前
5秒前
科研通AI5应助hahaha采纳,获得10
5秒前
lixiang完成签到,获得积分20
6秒前
9秒前
9秒前
9秒前
爬不起来发布了新的文献求助10
10秒前
楼藏鸟完成签到,获得积分10
11秒前
孔难破发布了新的文献求助10
13秒前
科研通AI5应助江峰采纳,获得10
14秒前
15秒前
124完成签到,获得积分10
16秒前
17秒前
李爱国应助嘻嘻采纳,获得10
17秒前
科研通AI2S应助任性雨筠采纳,获得10
17秒前
18秒前
发发完成签到 ,获得积分10
19秒前
heyheybaby发布了新的文献求助10
21秒前
23秒前
wyl发布了新的文献求助10
24秒前
等待戈多发布了新的文献求助30
24秒前
研友_VZG7GZ应助jiayou采纳,获得10
25秒前
25秒前
27秒前
27秒前
27秒前
嘻嘻发布了新的文献求助10
28秒前
ZiruiDing完成签到 ,获得积分10
29秒前
猴儿完成签到,获得积分20
29秒前
qiulong发布了新的文献求助10
30秒前
康师傅冰红茶完成签到,获得积分10
30秒前
高分求助中
Basic Discrete Mathematics 1000
Technologies supporting mass customization of apparel: A pilot project 600
Introduction to Strong Mixing Conditions Volumes 1-3 500
Tip60 complex regulates eggshell formation and oviposition in the white-backed planthopper, providing effective targets for pest control 400
A Field Guide to the Amphibians and Reptiles of Madagascar - Frank Glaw and Miguel Vences - 3rd Edition 400
China Gadabouts: New Frontiers of Humanitarian Nursing, 1941–51 400
The Healthy Socialist Life in Maoist China, 1949–1980 400
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 物理 生物化学 纳米技术 计算机科学 化学工程 内科学 复合材料 物理化学 电极 遗传学 量子力学 基因 冶金 催化作用
热门帖子
关注 科研通微信公众号,转发送积分 3799816
求助须知:如何正确求助?哪些是违规求助? 3345094
关于积分的说明 10323610
捐赠科研通 3061657
什么是DOI,文献DOI怎么找? 1680474
邀请新用户注册赠送积分活动 807093
科研通“疑难数据库(出版商)”最低求助积分说明 763462