An intra-tumoral niche maintains and differentiates stem-like CD8 T cells
An intra-tumoral niche maintains and differentiates stem-like CD8 T cells
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DOI：
10.1038/s41586-019-1836-5
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发表时间：
2019-12-19
期刊：
影响因子：
64.8
通讯作者：
Kissick, Haydn
中科院分区：
文献类型：
--
作者：
Jansen, Caroline S.;Prokhnevska, Nataliya;Kissick, Haydn
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相关（1-8）。然而，一些肿瘤具有高CD 8 T细胞浸润而另一些肿瘤没有的原因仍然不清楚。在这里，我们研究了维持CD 8 T细胞对人类癌症的反应的要求。我们发现肿瘤内的CD 8 T细胞由不同的终末分化细胞和干细胞样细胞群组成。在增殖时，干细胞样CD 8 T细胞产生更多终末分化的、表达效应分子的子细胞。对于许多T细胞浸润肿瘤，这种效应分化过程的发生至关重要。此外，我们发现这些干细胞样T细胞存在于肿瘤内密集的抗原呈递细胞龛中，并且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小生境，这表明小生境破坏可能是免疫逃逸的关键机制。
Tumour-infiltrating lymphocytes are associated with a survival benefit in several tumour types and with the response to immunotherapy(1-8). 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.