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肿瘤内微环境维持并分化干细胞样CD8 T细胞
2019-12-12 19:40

美国埃默里大学医学院Haydn Kissick研究小组的一项最新工作表明,肿瘤内的微环境维持并分化干细胞样CD8 T细胞。 该研究于2019年12月11日在线发表于国际一流学术期刊《自然》。

研究人员探究了维持CD8 T细胞反应抵御人类肿瘤所需的要求。研究人员发现肿瘤内的CD8 T细胞内由不同数量的终末分化和干细胞样细胞组成。增殖时,干细胞样CD8 T细胞产生更多末端分化的表达效应分子的子细胞。 对于许多T细胞浸润的肿瘤,至关重要的是发生这种效应分化过程。

此外,研究人员发现这些干细胞样T细胞驻留在肿瘤内的致密抗原呈递细胞微环境中,未能形成这些结构的肿瘤不会被T细胞广泛浸润。 进行性疾病患者缺乏这些免疫功能,这表明微环境破坏可能是免疫逃逸的关键机制。

据介绍,肿瘤浸润淋巴细胞与几种肿瘤类型的生存获益以及对免疫治疗的反应有关。 但是,目前尚不清楚某些肿瘤具有高CD8 T细胞浸润的原因。

附:英文原文

Title: An intra-tumoral niche maintains and differentiates stem-like CD8 T cells

Author: Caroline S. Jansen, Nataliya Prokhnevska, Viraj A. Master, Martin G. Sanda, Jennifer W. Carlisle, Mehmet Asim Bilen, Maria Cardenas, Scott Wilkinson, Ross Lake, Adam G. Sowalsky, Rajesh M. Valanparambil, William H. Hudson, Donald McGuire, Kevin Melnick, Amir I. Khan, Kyu Kim, Yun Min Chang, Alice Kim, Christopher P. Filson, Mehrdad Alemozaffar, Adeboye O. Osunkoya, Patrick Mullane, Carla Ellis, Rama Akondy, Se Jin Im, Alice O. Kamphorst, Adriana Reyes, Yuan Liu, Haydn Kissick

Issue&Volume: 2019-12-11

Abstract: Tumour-infiltrating lymphocytes are associated with a survival benefit in several tumour types and with the response to immunotherapy1,2,3,4,5,6,7,8. However, the reason some tumours have high CD8 T cell infiltration while others do not remains unclear. Here we investigate the requirements for maintaining a CD8 T cell response against human cancer. We find that CD8 T cells within tumours consist of distinct populations of terminally differentiated and stem-like cells. On proliferation, stem-like CD8 T cells give rise to more terminally differentiated, effector-molecule-expressing daughter cells. For many T cells to infiltrate the tumour, it is critical that this effector differentiation process occur. In addition, we show that these stem-like T cells reside in dense antigen-presenting-cell niches within the tumour, and that tumours that fail to form these structures are not extensively infiltrated by T cells. Patients with progressive disease lack these immune niches, suggesting that niche breakdown may be a key mechanism of immune escape.

DOI: 10.1038/s41586-019-1836-5

Source: https://www.nature.com/articles/s41586-019-1836-5

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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