Intratumoral CXCR5+CD8+T associates with favorable clinical outcomes and immunogenic contexture in gastric cancer

Wang, Jieti; Li, Ruochen; Cao, Yifan; Gu, Yun; Fang, Hanji; Fei, Yuchao; Lv, Kunpeng; He, Xingkang; Lin, Chao; Líu, Hao; Zhang, Heng; Li, He; He, Hongyong; Xu, Jiejie; Huang, Hua

doi:10.1038/s41467-021-23356-w

Cited by 46 publications

(38 citation statements)

References 40 publications

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“…Several studies have shown that tumors with a higher TMB can produce more neoantigens, which are more easily recognized by T cells and induce greater immune cytotoxic activity ( Rooney et al, 2015 ). In addition, multiple studies have shown that patients with positive expression of PD-L1 in tumors and infiltration of CD8 + T cells have longer overall survival times ( Wang et al, 2018 ; Wang et al, 2021 ), as was observed in our analysis.…”

Section: Resultssupporting

confidence: 87%

Analysis of DNA Repair-Related Prognostic Function and Mechanism in Gastric Cancer

Wang

Song

et al. 2022

Front. Cell Dev. Biol.

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DNA repair mechanisms have been proven to be essential for cells, and abnormalities in DNA repair could cause various diseases, such as cancer. However, the diversity and complexity of DNA repair mechanisms obscure the functions of DNA repair in cancers. In addition, the relationships between DNA repair, the tumor mutational burden (TMB), and immune infiltration are still ambiguous. In the present study, we evaluated the prognostic values of various types of DNA repair mechanisms and found that double-strand break repair through single-strand annealing (SSA) and nonhomologous end-joining (NHEJ) was the most prognostic DNA repair processes in gastric cancer (GC) patients. Based on the activity of these two approaches and expression profiles, we constructed a HR-LR model, which could accurately divide patients into high-risk and low-risk groups with different probabilities of survival and recurrence. Similarly, we also constructed a cancer-normal model to estimate whether an individual had GC or normal health status. The prognostic value of the HR-LR model and the accuracy of the cancer-normal model were validated in several independent datasets. Notably, low-risk samples, which had higher SSA and NHEJ activities, had more somatic mutations and less immune infiltration. Furthermore, the analysis found that low-risk samples had higher and lower methylation levels in CpG islands (CGIs) and open sea regions respectively, and had higher expression levels of programmed death-ligand 1 (PD-L1) and lower methylation levels in the promoter of the gene encoding PD-L1. Moreover, low-risk samples were characterized primarily by higher levels of CD4+ memory T cells, CD8+ naive T cells, and CD8+ TEM cells than those in high-risk samples. Finally, we proposed a decision tree and nomogram to help predict the clinical outcome of an individual. These results provide an improved understanding of the complexity of DNA repair, the TMB, and immune infiltration in GC, and present an accurate prognostic model for use in GC patients.

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Section: Resultssupporting

confidence: 87%

Analysis of DNA Repair-Related Prognostic Function and Mechanism in Gastric Cancer

Wang

Song

et al. 2022

Front. Cell Dev. Biol.

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“…It has been reported that intratumoral specific CD8 + T cell biomarkers can determine the prognosis and immunoevasive outcomes in ccRCC patients, which is a probable explanation for why ccRCC tumors progress despite a robust CD8 + T cell infiltration ( 23 , 50 , 51 ). However, the randomly selected markers might not reflect the heterogeneity of CD8 + T cells ( 50 , 51 , 64 ). In this study, WGCNA was used to identify CD8 + T cell related module genes, while the unsupervised clustering method was used to better identify novel CD8 + T cell-related molecular patterns.…”

Section: Discussionmentioning

confidence: 99%

CD8+ T Cell-Based Molecular Classification With Heterogeneous Immunogenomic Landscapes and Clinical Significance of Clear Cell Renal Cell Carcinoma

Jiang

Liu

et al. 2021

Front. Immunol.

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The tumor microenvironment (TME) exerts a high impact on tumor biology and immunotherapy. The heterogeneous phenotypes and the clinical significance of CD8+ T cells in TME have not been fully elucidated. Here, a comprehensive immunogenomic analysis based on multi-omics data was performed to investigate the clinical significance and tumor heterogeneity between CD8+ T cell-related molecular clusters. We identified two distinct molecular clusters of ccRCC (C1 and C2) in TCGA and validated in E-MTAB-1980 cohorts. The C1 cluster was characterized by unfavorable prognosis, increased expression levels of CD8+ T cell exhaustion markers, high immune infiltration levels as well as more immune escape mechanisms. The C2 cluster was featured by favorable prognosis, elevated expression levels of CD8+ T cell effector markers, low load of copy number loss and low frequency of 9p21.3 deletion. Moreover, the effect of molecular classifications on Nivolumab therapeutic efficacy in the CheckMate 025 cohort was examined, and the C2 cluster exhibited a better prognosis. Taken together, we determine two CD8+ T cell-related molecular clusters in ccRCC, and provide new insights for evaluating the functions of CD8+ T cells. Our molecular classification is a potential strategy for prognostic prediction and immunotherapeutic guidance for ccRCC patients.

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“…While PD-1 blockade combined with immune modulators, such as TGF-β1 inhibitor, might take patients more benefits than targeted PD-1 alone [ 6 ]. And it was also reported that some subsets of CD8+ T, such as CXCR5+CD8+ T [ 8 ], but not CD8+ T itself connected with better overall survival (OS) in patients with GC. Therefore, it is important to find out the key molecules that regulate immune modulators in TME or/and co-express molecular in CD8+ T that mediated its function.…”

Section: Introductionmentioning

confidence: 99%

Identification hub genes of consensus molecular subtype correlation with immune infiltration and predict prognosis in gastric cancer

Fang

et al. 2021

Discov Onc

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Gastric cancer (GC) has a great fatality rate, meanwhile, there is still a lack of available biomarkers for prognosis. The goal of the research was to discover key and novel potential biomarkers for GC. We screened for the expression of significantly altered genes based on survival rates from two consensus molecular subtypes (CMS) of GC. Subsequently, functional enrichment analysis showed these genes involved in many cancers. And we picked 6 hub genes that could both secreted in the tumor microenvironment and expression enhanced in immune cells. Then, Kaplan Meier survival and expression detected in the tumor pathological stage were utilized to clarify the prognostic of these 6 hub genes. The results indicated that OGN, CHRDL2, C2orf40, THBS4, CHRDL1, and ANGPTL1, respectively, were significantly associated with poor OS in GC patients. And their expression increased with cancer advanced. Moreover, immune infiltration analysis displayed that those hub genes expression positively with M2 macrophage, CD8+ T Cell, most immune inhibitors, and majority immunostimulators. In summary, our results suggested that OGN, CHRDL2, C2orf40, THBS4, CHRDL1, and ANGPTL1 were all potential biomarkers for GC prognosis and might also be potential therapeutic targets for GC.

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Intratumoral CXCR5+CD8+T associates with favorable clinical outcomes and immunogenic contexture in gastric cancer

Cited by 46 publications

References 40 publications

Analysis of DNA Repair-Related Prognostic Function and Mechanism in Gastric Cancer

Analysis of DNA Repair-Related Prognostic Function and Mechanism in Gastric Cancer

CD8+ T Cell-Based Molecular Classification With Heterogeneous Immunogenomic Landscapes and Clinical Significance of Clear Cell Renal Cell Carcinoma

Identification hub genes of consensus molecular subtype correlation with immune infiltration and predict prognosis in gastric cancer

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