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肿瘤组织驻留记忆 T 细胞在乳腺癌的控制和免疫治疗反应中的作用。

Tissue-resident memory T cells in breast cancer control and immunotherapy responses.

机构信息

Division of Research, Peter MacCallum Cancer Centre, University of Melbourne, Melbourne, Victoria, Australia.

Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Victoria, Australia.

出版信息

Nat Rev Clin Oncol. 2020 Jun;17(6):341-348. doi: 10.1038/s41571-020-0333-y. Epub 2020 Feb 28.


DOI:10.1038/s41571-020-0333-y
PMID:32112054
Abstract

The presence of tumour-infiltrating lymphocytes (TILs) is associated with favourable outcomes in patients with breast cancer as well as in those with other solid tumours. T cells make up a considerable proportion of TILs and current evidence suggests that CD8 T cells are a crucial determinant of favourable clinical outcomes. Studies involving tumour material from numerous solid tumour types, including breast cancer, demonstrate that the CD8 TILs include a subpopulation of tissue-resident memory T (T) cells. This subpopulation has features consistent with those of T cells, which have been described as having a role in peripheral immune surveillance and viral immunity in both humans and mice. Patients with early-stage triple-negative breast cancers harbouring greater numbers of T cells have a substantially improved prognosis and longer overall survival. Furthermore, patients with advanced-stage breast cancers with higher levels of T cells have increased response rates to anti-PD-1 antibodies. These findings have motivated efforts to explore whether CD8 T cells include tumour-specific T cells, their functional responses to cognate antigens and their role in responses to immune checkpoint inhibition. In this Review, we focus on the clinical significance of CD8 T cells and the potential ways that these cells can be targeted to improve the success of immunotherapeutic approaches in patients with breast cancer, as well as in those with other solid tumour types.

摘要

肿瘤浸润淋巴细胞(TILs)的存在与乳腺癌患者以及其他实体瘤患者的良好预后相关。T 细胞构成了 TILs 的相当大一部分,现有证据表明 CD8 T 细胞是良好临床结果的关键决定因素。涉及包括乳腺癌在内的多种实体瘤类型的肿瘤标本的研究表明,CD8 TIL 中包括一群组织驻留记忆 T(T)细胞。这群细胞具有与 T 细胞一致的特征,这些 T 细胞被描述为在人类和小鼠中具有外周免疫监视和抗病毒免疫的作用。患有早期三阴性乳腺癌且具有更多 T 细胞的患者具有显著改善的预后和更长的总生存期。此外,T 细胞水平较高的晚期乳腺癌患者对抗 PD-1 抗体的反应率增加。这些发现促使人们努力探索 CD8 T 细胞是否包含肿瘤特异性 T 细胞、它们对同源抗原的功能反应以及它们在免疫检查点抑制反应中的作用。在这篇综述中,我们重点关注 CD8 T 细胞的临床意义以及这些细胞被靶向以提高乳腺癌患者以及其他实体瘤类型患者免疫治疗方法成功的潜在方法。

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[3]
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[7]
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本文引用的文献

[1]
Atezolizumab plus nab-paclitaxel as first-line treatment for unresectable, locally advanced or metastatic triple-negative breast cancer (IMpassion130): updated efficacy results from a randomised, double-blind, placebo-controlled, phase 3 trial.

Lancet Oncol. 2019-11-27

[2]
Precursor exhausted T cells: key to successful immunotherapy?

Nat Rev Immunol. 2019-10-7

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Nat Rev Immunol. 2019-9-30

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Ann Oncol. 2019-12-1

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Tissue-resident memory CD8 T cells amplify anti-tumor immunity by triggering antigen spreading through dendritic cells.

Nat Commun. 2019-9-27

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Trends Immunol. 2019-6-26

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[10]
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Lancet Oncol. 2019-2-11

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