腫瘤內微環境維持並分化幹細胞樣CD8 T細胞

腫瘤內微環境維持並分化幹細胞樣CD8 T細胞

作者：

小柯機器人

發布時間：2019/12/12 19:40:52

美國埃默裡大學醫學院Haydn Kissick研究小組的一項最新工作表明，腫瘤內的微環境維持並分化幹細胞樣CD8 T細胞。 該研究於2019年12月11日在線發表於國際一流學術期刊《自然》。

研究人員探究了維持CD8 T細胞反應抵禦人類腫瘤所需的要求。研究人員發現腫瘤內的CD8 T細胞內由不同數量的終末分化和幹細胞樣細胞組成。增殖時，幹細胞樣CD8 T細胞產生更多末端分化的表達效應分子的子細胞。 對於許多T細胞浸潤的腫瘤，至關重要的是發生這種效應分化過程。

此外，研究人員發現這些幹細胞樣T細胞駐留在腫瘤內的緻密抗原呈遞細胞微環境中，未能形成這些結構的腫瘤不會被T細胞廣泛浸潤。 進行性疾病患者缺乏這些免疫功能，這表明微環境破壞可能是免疫逃逸的關鍵機制。

據介紹，腫瘤浸潤淋巴細胞與幾種腫瘤類型的生存獲益以及對免疫治療的反應有關。 但是，目前尚不清楚某些腫瘤具有高CD8 T細胞浸潤的原因。

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