CD8+CD226high T cells in liver metastases dictate the prognosis of colorectal cancer patients treated with chemotherapy and radical surgery

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外文摘要：CD226 has been reported to participate in the rescue of CD8+T cell dysfunction.In this study,we aimed to assess the prognostic value of CD226 in tumor-infiltrating lymphocytes(TILs)derived from colorectal cancer(CRC)liver metastases treated with chemotherapy and radical surgery.TILs from 43 metastases were isolated and analyzed ex vivo using flow cytometry.CD155 and CD3 levels in the tumor microenvironment were assessed by immunohistochemistry.Exploration and validation of biological processes highlighted in this study were performed by bioinformatics analysis of bulk RNA-seq results for 28 CRC liver metastases pretreated with chemotherapy as well as public gene expression datasets.CD226 expression contributes to the definition of the immune context in CRC liver metastases and primary tumors.CD226 on CD8+T cells was not specifically coexpressed with other immune checkpoints,such as PD1,TIGIT,and TIM3,in liver metastases.Multivariate Cox regression analysis revealed CD226 expression on CD8+T cells to be an independent prognostic factor(p=0.003),along with CD3 density at invasion margins(p=0.003)and TIGIT expression on CD4+T cells(p=0.019).CD155 was not associated with the prognostic value of CD226.Gene expression analysis in a validation dataset confirmed the prognostic value of CD226 in CRC liver metastases but not in primary tumors.Downregulation of CD226 on CD8+TILs in the liver microenvironment was restored by IL15 treatment.Overall,CD226 expression on liver metastasis-infiltrating CD8+T cells selectively contributes to immune surveillance of CRC liver metastases and has prognostic value for patients undergoing radical surgery.

外文关键词：

CD226 antigenColorectal NeoplasmsLiver metastasisLymphocytesTumor-Infiltrating

作者：

Julien Viot、Syrine Abdeljaoued、Angélique Vienot、Evan Seffar、Laurie Spehner、Adeline Bouard、Kamal Asgarov、Jean-René Pallandre、Elodie Renaude、Elodie Klajer、Chloé Molimard、Franck Monnien、Frederic Bibeau、Celia Turco、Bruno Heyd、Paul Peixoto、Eric Hervouet、Romain Loyon、Alexandre Doussot、Christophe Borg、Marie Kroemer

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作者单位：

Department of Medical Oncology,Biotechnology and Immuno-Oncology Platform,University Hospital of Besancon,Besancon,France

INSERM,EFS BFC,UMR1098,RIGHT,University of Franche-Comté,Interactions Greffon-Hôte-Tumeur/Ingénierie Cellulaire et Génique,Besancon,France

Department of Pathology,University Hospital of Besancon,Besancon,France

Department of Surgery,University Hospital of Besancon,Besancon,France

EPIGENEXP platform,University of Bourgogne Franche-Comté,Besancon,France

Department of Pharmacy,University Hospital of Besancon,Besancon,France

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出版年：

2023

DOI：

10.1038/s41423-023-00978-2

中国免疫学杂志(英文版)

中国免疫学会

中国免疫学杂志(英文版)

CSTPCDCSCDSCI

影响因子：0.731

ISSN：1672-7681

年,卷(期)：2023.20(4)

参考文献量45