scRNA-seq of gastric tumor shows complex intercellular interaction with an alternative T cell exhaustion trajectory

Sun, Keyong; Xu, Runda; Ma, Fuhai; Yang, Ning; Li, Yang; Xiao-feng, Sun; Jin, Peng; Kang, Wenzhe; Jia, Lemei; Xiong, Jianping; Hu, Haitao; Tian, Yantao; Lan, Xun

doi:10.1038/s41467-022-32627-z

Cited by 63 publications

(53 citation statements)

References 70 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In gastric cancer, LAMP3+ DCs were predicted to deliver attracting and activating signals to lymphocytes. However, LAMP3+ DCs inhibited anti-tumor T cell activity through a high expression of PD-L1 ( 31 ). In lymph node metastasized tumors, LAMP3+ DCs showed a stronger interaction with Tregs to enhance immunosuppression ( 32 ).…”

Section: Discussionmentioning

confidence: 99%

LAMP3 expression in the liver is involved in T cell activation and adaptive immune regulation in hepatitis B virus infection

Wang

Jin

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

BackgroundThe disease burden caused by chronic hepatitis B virus (HBV) infection is still heavy, and the current treatment scheme has not achieved a complete cure. Changes in natural and adaptive immunity usually accompany chronic HBV infection. As a marker expressed on dendritic cells (DCs), whether lysosome-associated membrane glycoprotein 3 (LAMP3) participates in chronic HBV infection deserves further analysis.MethodsWe retrieved chronic HBV infection transcriptional information from the Gene Expression Omnibus (GEO) database. The LAMP3 expression in the liver of patients with chronic hepatitis B (CHB) was analyzed in three GEO datasets and confirmed in our validation cohort (27 patients with CHB). Differentially expressed genes were obtained from one CHB cohort by comparing LAMP3high and LAMP3low expression subgroups. These genes underwent Gene Ontology, Kyoto Encyclopedia of Genes and Genomes analysis, and Gene Set Enrichment Analysis to decipher the influence of LAMP3 on the biological process and immunity changes in HBV infection. Furthermore, we investigated the potential relationship between LAMP3 levels, the abundance of infiltrating immune cells, and liver dysfunction.ResultsCompared to healthy controls, LAMP3 expression was upregulated in the transcriptional profiles of the liver in patients with CHB. The high LAMP3 expression was related to T cell activation and the chemokine signaling pathway. The LAMP3 gene was positively linked to marker sets of infiltrating activated regulatory T cells (Treg), T cell exhaustion, monocytes, and DCs. Moreover, CHB patients with high LAMP3 expression had unfavorable liver dysfunction.ConclusionsLAMP3 is a gene related to HBV infection, which might be involved in HBV infection by regulating T cell activation and adaptive immune response.

show abstract

Section: Discussionmentioning

confidence: 99%

LAMP3 expression in the liver is involved in T cell activation and adaptive immune regulation in hepatitis B virus infection

Wang

Jin

et al. 2023

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…( 76 ) performed single-cell sequencing on a variety of tumor-infiltrating T cells, including gastric cancer and esophageal cancer, and found that the exhausted T cells were mainly from effector memory T cells and tissue-resident T cells. Recent study has found that the exhaustion of CD8 + T cells is accompanied by an increase in the number of Tc17 cells with poor cytolytic capacity ( 77 ).The scRNA-seq of gastric tumor also showed Tc17 exhaustion pathway originating from Trm ( 78 ). Another single-cell sequencing results showed that Trm cells could be divided into three subsets: Hobit-enriched CD103 hi PD-1 lo Trm, Granzyme K-enriched CD103 lo PD-1 hi Trm, and CD103 hi PD-1 hi CTLA hi LAG3 hi TIGIT hi Trm, while the last subset is considered as exhaustion-related subtype ( 79 ).…”

Section: Overview Of Tissue-resident Memory T Cellsmentioning

confidence: 99%

Tissue-resident memory T cells in gastrointestinal tumors: turning immune desert into immune oasis

et al. 2023

View full text Add to dashboard Cite

Tissue-resident memory T cells (Trm) are a particular type of T cell subgroup, which stably reside in tissues and have been revealed to be the most abundant memory T cell population in various tissues. They can be activated in the local microenvironment by infection or tumor cells and rapidly clean them up to restore homeostasis of local immunity in gastrointestinal tissues. Emerging evidence has shown that tissue-resident memory T cells have great potential to be mucosal guardians against gastrointestinal tumors. Therefore, they are considered potential immune markers for immunotherapy of gastrointestinal tumors and potential extraction objects for cell therapy with essential prospects in clinical translational therapy. This paper systematically reviews the role of tissue-resident memory T cells in gastrointestinal tumors and looks to the future of their prospect in immunotherapy to provide a reference for clinical application.

show abstract

“…Specifically in digestive system cancers, TAMs are similarly thought to have mutual modulation with T cells, including but not limited to blocking the recruitment and priming of T cells and resulting in T-cell exclusion within the TME. In GC, TAMs and LAMP3 + dendritic cells (DCs) are involved in mediating T-cell activity and form intercellular interaction hubs with tumor-associated stromal cells[ 37 ]. IL-10 + TAM infiltration yielded an immunoevasive TME featured by Treg cell infiltration and CD8 + T-cell dysfunction[ 38 ].…”

Section: Tam Status In Tumorsmentioning

confidence: 99%

Role of tumor-associated macrophages in common digestive system malignant tumors

Shen¹,

Chen²,

Li³

et al. 2023

World J Gastrointest Oncol

View full text Add to dashboard Cite

Many digestive system malignant tumors are characterized by high incidence and mortality rate. Increasing evidence has revealed that the tumor microenvironment (TME) is involved in cancer initiation and tumor progression. Tumor-associated macrophages (TAMs) are a predominant constituent of the TME, and participate in the regulation of various biological behaviors and influence the prognosis of digestive system cancer. TAMs can be mainly classified into the antitumor M1 phenotype and protumor M2 phenotype. The latter especially are crucial drivers of tumor invasion, growth, angiogenesis, metastasis, immunosuppression, and resistance to therapy. TAMs are of importance in the occurrence, development, diagnosis, prognosis, and treatment of common digestive system malignant tumors. In this review, we summarize the role of TAMs in common digestive system malignant tumors, including esophageal, gastric, colorectal, pancreatic and liver cancers. How TAMs promote the development of tumors, and how they act as potential therapeutic targets and their clinical applications are also described.

show abstract

scRNA-seq of gastric tumor shows complex intercellular interaction with an alternative T cell exhaustion trajectory

Cited by 63 publications

References 70 publications

LAMP3 expression in the liver is involved in T cell activation and adaptive immune regulation in hepatitis B virus infection

LAMP3 expression in the liver is involved in T cell activation and adaptive immune regulation in hepatitis B virus infection

Tissue-resident memory T cells in gastrointestinal tumors: turning immune desert into immune oasis

Role of tumor-associated macrophages in common digestive system malignant tumors

Contact Info

Product

Resources

About