创作:Lexi 审核:Lexi 2019年07月08日
  • 分析35个结直肠癌(CRC)组织、26个肿瘤相关淋巴结、17份健康结直肠粘膜、19份外周血样的免疫细胞标记物、肿瘤浸润淋巴细胞功能、转录组和空间分布;
  • 发现一群Lin–CD7+CD127–CD56+CD45RO+淋巴细胞群体在CRC组织中富集,且有细胞杀伤活力;
  • 该细胞群体表现出组织驻留表型(CD103+CD69+),且在DNA错配修复(MMR)缺陷的CRC中高度富集;
  • 该细胞群在肿瘤组织中的出现与肿瘤相关杀伤T细胞、辅助T细胞、 γδ T细胞的肿瘤浸润程度相关。
Gut [IF:23.059]

High-dimensional cytometric analysis of colorectal cancer reveals novel mediators of antitumour immunity



2019-07-03, Article

Abstract & Authors:展开

Objective: A comprehensive understanding of anticancer immune responses is paramount for the optimal application and development of cancer immunotherapies. We unravelled local and systemic immune profiles in patients with colorectal cancer (CRC) by high-dimensional analysis to provide an unbiased characterisation of the immune contexture of CRC.
Design : Thirty-six immune cell markers were simultaneously assessed at the single-cell level by mass cytometry in 35 CRC tissues, 26 tumour-associated lymph nodes, 17 colorectal healthy mucosa and 19 peripheral blood samples from 31 patients with CRC. Additionally, functional, transcriptional and spatial analyses of tumour-infiltrating lymphocytes were performed by flow cytometry, single-cell RNA-sequencing and multispectral immunofluorescence.
Results : We discovered that a previously unappreciated innate lymphocyte population (Lin–CD7+CD127–CD56+CD45RO+) was enriched in CRC tissues and displayed cytotoxic activity. This subset demonstrated a tissue-resident (CD103+CD69+) phenotype and was most abundant in immunogenic mismatch repair (MMR)-deficient CRCs. Their presence in tumours was correlated with the infiltration of tumour-resident cytotoxic, helper and γδ T cells with highly similar activated (HLA-DR+CD38+PD-1+) phenotypes. Remarkably, activated γδ T cells were almost exclusively found in MMR-deficient cancers. Non-activated counterparts of tumour-resident cytotoxic and γδ T cells were present in CRC and healthy mucosa tissues, but not in lymph nodes, with the exception of tumour-positive lymph nodes.
Conclusion : This work provides a blueprint for the understanding of the heterogeneous and intricate immune landscape of CRC, including the identification of previously unappreciated immune cell subsets. The concomitant presence of tumour-resident innate and adaptive immune cell populations suggests a multitargeted exploitation of their antitumour properties in a therapeutic setting.

First Authors:
Natasja L de Vries

Correspondence Authors:
Noel F C C de Miranda

All Authors:
Natasja L de Vries,Vincent van Unen,Marieke E Ijsselsteijn,Tamim Abdelaal,Ruud van der Breggen,Arantza Farina Sarasqueta,Ahmed Mahfouz,Koen C M J Peeters,Thomas Höllt,Boudewijn P F Lelieveldt,Frits Koning,Noel F C C de Miranda