Dataset Information

Identification and validation of an immunogenic subtype of gastric cancer with abundant intratumoural CD103⁺CD8⁺ T cells conferring favourable prognosis.

ABSTRACT:

Background

Intratumoural CD103⁺CD8⁺ T cells have been linked to prolonged survival in several malignancies. However, the clinical significance of CD103⁺CD8⁺ T cells in gastric cancer remains unexplored.

Methods

Gastric cancer tissues from Zhongshan Hospital and data from Gene Expression Omnibus were obtained and analysed. Immunohistochemistry and flow cytometry were performed to detect the number and phenotypical characteristics of CD103⁺CD8⁺ T cells. The effect of programmed cell death protein-1 (PD-1) blockade on CD103⁺CD8⁺ T cells was evaluated with the use of an in vitro study based on fresh tumour tissues.

Results

CD103⁺CD8⁺ T cells predicted superior overall survival and provided better prognostic power than total CD8⁺ T cells in gastric cancer. Patients with high CD103⁺CD8⁺ T cell infiltration also gained more benefit from adjuvant chemotherapy. Flow cytometry analysis showed that CD103⁺CD8⁺ T cells exerted superior anti-tumour effects with stronger retention capacity and cytotoxicity. Moreover, an in vitro study showed that CD103⁺CD8⁺ T cells were more functionally restored after PD-1 blockade than CD103^-CD8⁺ T cells.

Conclusions

CD103⁺CD8⁺ T cells might be a useful marker to predict prognosis and therapeutic efficacy for gastric cancer patients. Efforts to increase intratumoural CD103⁺CD8⁺ T cell frequency might be a novel therapeutic strategy in gastric cancer.

SUBMITTER: Li R

PROVIDER: S-EPMC7217759 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

Identification and validation of an immunogenic subtype of gastric cancer with abundant intratumoural CD103<sup>+</sup>CD8<sup>+</sup> T cells conferring favourable prognosis.

Li Ruochen R Liu Hao H Cao Yifan Y Wang Jieti J Chen Yifan Y Qi Yangyang Y Lv Kunpeng K Liu Xin X Yu Kuan K Lin Chao C Zhang Heng H He Hongyong H Li He H Chen Lingli L Shen Zhenbin Z Qin Jing J Zhang Weijuan W Sun Yihong Y Xu Jiejie J

British journal of cancer 20200324 10

<h4>Background</h4>Intratumoural CD103<sup>+</sup>CD8<sup>+</sup> T cells have been linked to prolonged survival in several malignancies. However, the clinical significance of CD103<sup>+</sup>CD8<sup>+</sup> T cells in gastric cancer remains unexplored.<h4>Methods</h4>Gastric cancer tissues from Zhongshan Hospital and data from Gene Expression Omnibus were obtained and analysed. Immunohistochemistry and flow cytometry were performed to detect the number and phenotypical characteristics of CD103 ...[more]

PMID: 32205862

Similar Datasets

Project description:BackgroundGastric cancer (GC) is a leading malignant disease in numerous countries, including Taiwan with limited therapeutic options. Animal viruses including oncolytic avian reovirus (ARV) have the possibility to avoid pre-existing immunity in humans, while being safe and immunostimulatory. Here, we provide a novel insight into oncolytic ARV and UV-ARV-sensitized patient's peripheral blood mononuclear cells (P-PBMCs) and tumor infiltrating lymphocytes (TILs) killing primary GC (PGC) cells through the surface TLR3 and TRAIL/DR4/DR5 immunogenic apoptosis pathway.MethodsWe conducted a comprehensive study to reveal whether ARV- or UV-inactivated ARV (UV-ARV)-modulated P-PBMCs or TILs killing ARV- and UV-ARV-sensitized AGS cells and PGC cells derived from clinical patients and to investigate the regulation of surface TLR3 receptor and upstream signaling pathways. Apoptosis analysis by flow cytometry and Western blot, suppression of signal pathway by specific inhibitors, in situ proximity ligation assay (PLA), time-resolved flurometry and lactate dehydrogenase (LDH) cytotoxicity assays, and an in vitro co-culture model were established to study the interplay between ARV- and UV-ARV-sensitized P-PBMCs and TILs to kill PGC cells and their upstream pathways.ResultsOur results reveal that increased levels of DR4 and DR5 were observed in ARV and UV-ARV sensitized PGC cells through the TLR3/p38/p53 signaling pathway. Importantly, we found that the σC protein of ARV or UV-ARV interacted with surface TLR3 of CD8+ TILs, thereby triggering the TLR3/NF-κB/IFN-γ/TRAIL signaling pathway which induces immunogenic apoptosis of PGC cells. This study sheds further light on the molecular basis behind ARV oncolysis and facilitates the ARV or UV-ARV as a cancer therapeutic.ConclusionsThe study provides novel insights into ARV- or UV-ARV-sensitized P-PBMCs and CD8+ TILs to kill PGC cells through the immunogenic apoptosis pathway. We conclude that P-PBMCs can easily be obtained from GC patients and provide a rich source as TILs to kill PGC cells.

Dataset Information

Identification and validation of an immunogenic subtype of gastric cancer with abundant intratumoural CD103⁺CD8⁺ T cells conferring favourable prognosis.

Background

Methods

Results

Conclusions

Publications

Identification and validation of an immunogenic subtype of gastric cancer with abundant intratumoural CD103<sup>+</sup>CD8<sup>+</sup> T cells conferring favourable prognosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Identification and validation of an immunogenic subtype of gastric cancer with abundant intratumoural CD103+CD8+ T cells conferring favourable prognosis.

Background

Methods

Results

Conclusions

Publications

Identification and validation of an immunogenic subtype of gastric cancer with abundant intratumoural CD103<sup>+</sup>CD8<sup>+</sup> T cells conferring favourable prognosis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Identification and validation of an immunogenic subtype of gastric cancer with abundant intratumoural CD103⁺CD8⁺ T cells conferring favourable prognosis.