scholarly journals Immune infiltrating cells in cholangiocarcinoma may become clinical diagnostic markers: based on bioinformatics analysis.

2021 ◽  
Author(s):  
yongwei Zhang ◽  
Sihan Chen ◽  
Jun Li ◽  
Wei Dai ◽  
yeben Qian
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Visual Analysis ◽  
Immune Cell ◽  
Liver Tumors ◽  
Data Set ◽  
Expression Levels ◽  
Normal Tissues ◽  
Tumor Tissues

Abstract Background: intrahepatic cholangiocarcinoma (ICC) is a malignant tumor originating from the secondary bile duct and its branch epithelium. Among primary liver tumors, the incidence of ICC is second only to hepatocellular carcinoma. tumor microenvironment can regulate the occurrence and development of tumors. This study is dedicated to finding more markers that can diagnose ICC by finding the differential tumor microenvironment cells between ICC and normal tissues. Methods: We wanted to study the infiltration of immune cells between the cholangiocarcinoma of the same patient and its paired non-tumor tissues, to explore the difference of immune cells in the tumor microenvironment and adjacent non-tumor tissues in the same organism. So, we searched the relevant data of patients with ICC from the GEO database and found that the GSE45001 data set meets our research needs. CIBERSORT database is used to calculate immune cell composition. Finally, perform visual analysis and data statistics to find out the differentially expressed immune cells. Results: we found that the expression levels of Dendritic cells activated, Macrophages M2 and T cells regulatory (Tregs) in ICC were higher than normal tissues and the expression levels of Macrophages M1, Monocytes and T cells follicular helper in ICC were lower than normal tissues. Conclusion: These 6 types of immune cells are expected to become molecular markers for clinical diagnosis of ICC.

scholarly journals Immune infiltrating cells in cholangiocarcinoma may become clinical diagnostic markers: based on bioinformatics analysis.

2021 ◽  
Author(s):  
yongwei Zhang ◽  
Sihan Chen ◽  
Jun Li ◽  
Wei Dai ◽  
yeben Qian
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Visual Analysis ◽  
Immune Cell ◽  
Liver Tumors ◽  
Data Set ◽  
Expression Levels ◽  
Normal Tissues ◽  
Tumor Tissues

Abstract Background: intrahepatic cholangiocarcinoma (ICC) is a malignant tumor originating from the secondary bile duct and its branch epithelium. Among primary liver tumors, the incidence of ICC is second only to hepatocellular carcinoma. tumor microenvironment can regulate the occurrence and development of tumors. This study is dedicated to finding more markers that can diagnose ICC by finding the differential tumor microenvironment cells between ICC and normal tissues. Methods: We wanted to study the infiltration of immune cells between the cholangiocarcinoma of the same patient and its paired non-tumor tissues, to explore the difference of immune cells in the tumor microenvironment and adjacent non-tumor tissues in the same organism. So, we searched the relevant data of patients with ICC from the GEO database and found that the GSE45001 data set meets our research needs. CIBERSORT database is used to calculate immune cell composition. Finally, perform visual analysis and data statistics to find out the differentially expressed immune cells. Results: we found that the expression levels of Dendritic cells activated, Macrophages M2 and T cells regulatory (Tregs) in ICC were higher than normal tissues and the expression levels of Macrophages M1, Monocytes and T cells follicular helper in ICC were lower than normal tissues. Conclusion: These 6 types of immune cells are expected to become molecular markers for clinical diagnosis of ICC.

scholarly journals Immune infiltrating cells in cholangiocarcinoma may become clinical diagnostic markers: based on bioinformatics analysis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yongwei Zhang ◽  
Sihan Chen ◽  
Jun Li ◽  
Wei Dai ◽  
Yeben Qian
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Visual Analysis ◽  
Immune Cell ◽  
Liver Tumors ◽  
Data Set ◽  
Expression Levels ◽  
Normal Tissues ◽  
Tumor Tissues

Abstract Background Intrahepatic cholangiocarcinoma (ICC) is a malignant tumor originating from the secondary bile duct and its branch epithelium. Among primary liver tumors, the incidence of ICC is second only to hepatocellular carcinoma. Tumor microenvironment can regulate the occurrence and development of tumors. This study is dedicated to finding more markers that can diagnose ICC by finding the differential tumor microenvironment cells between ICC and normal tissues. Methods We wanted to study the infiltration of immune cells between the cholangiocarcinoma of the same patient and its paired non-tumor tissues, to explore the difference of immune cells in the tumor microenvironment and adjacent non-tumor tissues in the same organism. So, we searched the relevant data of patients with ICC from the GEO database and found that the GSE45001 data set meets our research needs. CIBERSORT database is used to calculate immune cell composition. Finally, perform visual analysis and data statistics to find out the differentially expressed immune cells. Results We found that the expression levels of dendritic cells activated, macrophages M2, and T cells regulatory (Tregs) in ICC were higher than normal tissues, and the expression levels of macrophages M1, monocytes, and T cells follicular helper in ICC were lower than normal tissues. Conclusion These 6 types of immune cells are expected to become molecular markers for clinical diagnosis of ICC.

scholarly journals Immune Infiltrating Cells in Cholangiocarcinoma May Become Clinical Diagnostic Markers: Based on Bioinformatics Analysis.

2020 ◽  
Author(s):  
Yongwei Zhang ◽  
Sihan Chen ◽  
Jun Li ◽  
Wei Dai ◽  
Yeben Qian
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Immune Cells ◽  
Visual Analysis ◽  
Immune Cell ◽  
Liver Tumors ◽  
Data Set ◽  
Expression Levels ◽  
Normal Tissues ◽  
Tumor Tissues

Abstract Background: intrahepatic cholangiocarcinoma (ICC) is a malignant tumor originating from the secondary bile duct and its branch epithelium. Among primary liver tumors, the incidence of ICC is second only to hepatocellular carcinoma. tumor microenvironment can regulate the occurrence and development of tumors. This study is dedicated to finding more markers that can diagnose ICC by finding the differential tumor microenvironment cells between ICC and normal tissues. Methods: We wanted to study the infiltration of immune cells between the cholangiocarcinoma of the same patient and its paired non-tumor tissues, to explore the difference of immune cells in the tumor microenvironment and adjacent non-tumor tissues in the same organism. So, we searched the relevant data of patients with ICC from the GEO database and found that the GSE45001 data set meets our research needs. CIBERSORT database is used to calculate immune cell composition. Finally, perform visual analysis and data statistics to find out the differentially expressed immune cells.Results: we found that the expression levels of Dendritic cells activated, Macrophages M2 and T cells regulatory (Tregs) in ICC were higher than normal tissues and the expression levels of Macrophages M1, Monocytes and T cells follicular helper in ICC were lower than normal tissues. Conclusion: These 6 types of immune cells are expected to become molecular markers for clinical diagnosis of ICC.

scholarly journals CDCA3 Is a Novel Prognostic Biomarker Associated with Immune Infiltration in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Zhihuai Wang ◽  
Shuai Chen ◽  
Gaochao Wang ◽  
Sun Li ◽  
Xihu Qin
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Immune Cell ◽  
Disease Free Survival ◽  
In Silico Analysis ◽  
Gene Markers ◽  
Free Survival ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Tumor Tissues

Cell division cycle-associated protein-3 (CDCA3) contributes to the regulation of the cell cycle. CDCA3 plays an important role in the carcinogenesis of various cancers; however, the association between CDCA3 expression, prognosis of patients, and immune infiltration in the tumor microenvironment is still unknown. Here, we demonstrated that CDCA3 was differentially expressed between the tumor tissues and corresponding normal tissues using in silico analysis in the ONCOMINE and Tumor Immune Estimation Resource (TIMER) databases. We analyzed the relationship between the expression of CDCA3 and prognosis of patients with hepatocellular carcinoma (HCC) using the Kaplan–Meier plotter database and Gene Expression Profiling Interactive Analysis (GEPIA). Furthermore, we determined the prognostic value of CDCA3 expression using univariate and multivariate analyses. We observed that CDCA3 expression closely correlated with immune infiltration and gene markers of infiltrating immune cells in the TIMER database. CDCA3 was highly expressed in the tumor tissues than in the adjacent normal tissues in various cancers, including HCC. Increased expression of CDCA3 was accompanied by poorer overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). The correlation between CDCA3 expression and OS and disease-free survival (DFS) was also studied using GEPIA. CDCA3 expression was associated with the levels of immune cell infiltration and was positively correlated with tumor purity. Moreover, CDCA3 expression was associated with gene markers such as PD-1, CTLA4, LAG3, and TIM-3 from exhausted T cells, CD3D, CD3E, and CD2 from T cells, and TGFB1 and CCR8 located on the surface of Tregs. Thus, we demonstrated that CDCA3 may be a potential target and biomarker for the management and diagnosis of HCC.

scholarly journals Myeloid Immune Cells CARriying a New Weapon Against Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Rodrigo Nalio Ramos ◽  
Samuel Campanelli Freitas Couto ◽  
Theo Gremen M. Oliveira ◽  
Paulo Klinger ◽  
Tarcio Teodoro Braga ◽  
...  
Keyword(s):  
Gene Therapy ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Solid Tumors ◽  
Immune Cells ◽  
Scientific Community ◽  
Immune Cell ◽  
Clinical Results ◽  
Mononuclear Phagocytes ◽  
Soluble Factors

Chimeric antigen receptor (CAR) engineering for T cells and natural killer cells (NK) are now under clinical evaluation for the treatment of hematologic cancers. Although encouraging clinical results have been reported for hematologic diseases, pre-clinical studies in solid tumors have failed to prove the same effectiveness. Thus, there is a growing interest of the scientific community to find other immune cell candidate to express CAR for the treatment of solid tumors and other diseases. Mononuclear phagocytes may be the most adapted group of cells with potential to overcome the dense barrier imposed by solid tumors. In addition, intrinsic features of these cells, such as migration, phagocytic capability, release of soluble factors and adaptive immunity activation, could be further explored along with gene therapy approaches. Here, we discuss the elements that constitute the tumor microenvironment, the features and advantages of these cell subtypes and the latest studies using CAR-myeloid immune cells in solid tumor models.

scholarly journals CCR4, CCR8, and P2RY14 as Prognostic Factors in Head and Neck Squamous Cell Carcinoma Are Involved in the Remodeling of the Tumor Microenvironment

2021 ◽  
Vol 11 ◽  
Author(s):  
Liangliang Meng ◽  
Xiaoxi He ◽  
Quan Hong ◽  
Bo Qiao ◽  
Xiao Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
T Cells ◽  
B Cells ◽  
Tumor Microenvironment ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Protein Level ◽  
Hub Genes ◽  
Normal Tissues ◽  
Tumor Tissues

The tumor microenvironment (TME) plays a critical role in the initiation and progression of cancer. However, the specific mechanism of its regulation in head and neck squamous cell carcinoma (HNSCC) remains unclear. In this study, we first applied the ESTIMATE method to calculate the immune and stromal scores in patients’ tumor tissues from The Cancer Genome Atlas (TCGA) database. GSE41613, GSE30784, and GSE37991 data sets from the Gene Expression Omnibus (GEO) database were recruited for further validation. Differentially expressed genes (DEGs) were identified and then analyzed by Cox regression analysis and protein-protein interaction (PPI) network construction. DEGs significantly associated with prognosis and TME will be identified as hub genes. These genes were also validated at the protein level by immunohistochemical analysis of 10 pairs of primary tumor tissues and the adjacent normal tissues from our institution. The relationship between hub genes expression and immune cell fraction estimated by CIBERSORT software was also examined. 275 DEGs were significantly associated with TME. CCR4, CCR8, and P2RY14 have then identified as hub genes by intersection Cox and PPI analysis. Further investigation revealed that the expression of CCR4, CCR8, and P2RY14 was negatively correlated with clinicopathological characteristics (clinical stage, T stage) and positively associated with survival in HNSCC patients, especially in male patients. The expression of CCR8 and P2RY14 was lower in males than in females. CCR8 and P2RY14 were differentially expressed in tumor tissues than normal tissues, and the results were validated at the protein level by immunohistochemistry experiments. Gene set enrichment analysis (GSEA) showed that the high expression groups’ hub genes were mainly enriched for immune-related activities. In the low-expression groups, genes were primarily enriched in metabolic pathways. CIBERSORT results showed that the expression of these genes was all negatively correlated with the fraction of memory B cells and positively correlated with the fraction of the other four cells, including naive B cells, resting T cells CD4 memory, T cells follicular helper, and T cells regulatory (Tregs). The results suggest that CCR4, CCR8, and P2RY14 may be responsible for maintaining the immune dominance of TME, thus leading to a better prognosis.

scholarly journals Single-cell Map of Diverse Immune Phenotypes Driven by the Tumor Microenvironment

2017 ◽  
Author(s):  
Elham Azizi ◽  
Ambrose J. Carr ◽  
George Plitas ◽  
Andrew E. Cornish ◽  
Catherine Konopacki ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Single Cell ◽  
Cancer Progression ◽  
Immune Cells ◽  
Immune Cell ◽  
Phenotypic Diversity ◽  
Macrophage Polarization ◽  
Sequencing Data ◽  
Significant Similarity

SUMMARYKnowledge of immune cell phenotypes in the tumor microenvironment is essential for understanding mechanisms of cancer progression and immunotherapy response. We created an immune map of breast cancer using single-cell RNA-seq data from 45,000 immune cells from eight breast carcinomas, as well as matched normal breast tissue, blood, and lymph node. We developed a preprocessing pipeline, SEQC, and a Bayesian clustering and normalization method, Biscuit, to address computational challenges inherent to single-cell data. Despite significant similarity between normal and tumor tissue-resident immune cells, we observed continuous tumor-specific phenotypic expansions driven by environmental cues. Analysis of paired single-cell RNA and T cell receptor (TCR) sequencing data from 27,000 additional T cells revealed the combinatorial impact of TCR utilization on phenotypic diversity. Our results support a model of continuous activation in T cells and do not comport with the macrophage polarization model in cancer, with important implications for characterizing tumor-infiltrating immune cells.

scholarly journals The bioinformatics and experimental analysis of AlkB family for prognosis and immune cell infiltration in hepatocellular carcinoma

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12123
Author(s):  
Bi Peng ◽  
Yuanliang Yan ◽  
Zhijie Xu
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Metal Ion ◽  
Immune Cell ◽  
Disease Free Survival ◽  
Normal Liver ◽  
Expression Levels ◽  
Normal Tissues ◽  
Molecular Profiles

Background Serving as N6-methyladenosine demethylases, the AlkB family is involved in the tumorigenesis of hepatocellular carcinoma (HCC). However, the molecular profiles and clinical values of the AlkB family in HCC are not well known. Methods Several bioinformatics tools and in vitro experiments were used to identify the immune-related profiles and prognostic values of AlkB family in HCC. Results In this study expression levels of ALKBH1/2/3/4/7 were all remarkably increased in HCC tissues when compared with normal tissues. Quantitative PCR (qPCR) and immunohistochemistry were used to validate the expression of AlkB family members in HCC tissues and normal liver tissues. In addition, high expression levels of ALKBH4 were negatively correlated with overall survival (OS) and disease-free survival (DFS) in patients with HCC. Increased ALKBH4 was also associated with pathological stage in HCC patients. The molecular profiles of AlkB family in HCC were mainly associated with peptidyl-serine modification, peptidyl-tyrosine modification, regulation of metal ion transport, etc. Furthermore, tumor-infiltrating immune cell analysis indicated that ALKBH1/2/3/4/5/6/7/8 and FTO were related to the infiltration of different immune cell, such as CD8+ T cells, macrophages, neutrophils, dendritic cells and CD4+ T cells. We also discovered that the methylation levels of ALKBH1/2/4/5/6/8 and FTO were remarkably reduced in HCC tissues. Conclusions Collectively, our findings may deepen the understanding of specific molecular profiles of the AlkB family in HCC pathology. In particular, ALKBH4 could serve as a promising prognostic candidate for treating HCC, and these results might potentiate the development of more reliable therapeutic strategies for patients with HCC.

scholarly journals Recruitment and Expansion of Tregs Cells in the Tumor Environment—How to Target Them?

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1850
Author(s):  
Justine Cinier ◽  
Margaux Hubert ◽  
Laurie Besson ◽  
Anthony Di Roio ◽  
Céline Rodriguez ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Tumor Microenvironment ◽  
Poor Prognosis ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
Major Function ◽  
Normal Tissues ◽  
Tumor Environment ◽  
Plastic Transformation

Regulatory T cells (Tregs) are present in a large majority of solid tumors and are mainly associated with a poor prognosis, as their major function is to inhibit the antitumor immune response contributing to immunosuppression. In this review, we will investigate the mechanisms involved in the recruitment, amplification and stability of Tregs in the tumor microenvironment (TME). We will also review the strategies currently developed to inhibit Tregs’ deleterious impact in the TME by either inhibiting their recruitment, blocking their expansion, favoring their plastic transformation into other CD4+ T-cell subsets, blocking their suppressive function or depleting them specifically in the TME to avoid severe deleterious effects associated with Treg neutralization/depletion in the periphery and normal tissues.

scholarly journals 492 Integration of high dimensional datasets in an immunocompetent mammary mouse model reveals pathways of tolerance and resistance to immune checkpoint blockade

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A528-A528
Author(s):  
Lin Ma ◽  
Jian-Hua Mao ◽  
Mary Helen Barcellos-Hoff ◽  
Jade Moore
Keyword(s):  
Tumor Microenvironment ◽  
Immune Cells ◽  
Transforming Growth Factor ◽  
Immune Cell ◽  
Systemic Disease ◽  
Ct Imaging ◽  
High Dimensional ◽  
Cytokine Signaling ◽  
Immune Infiltrate ◽  
Pet Ct

BackgroundCheckpoint inhibitors can induce robust and durable responses in a subset of patients. Extending this benefit to more patients could be facilitated by better understanding of how interacts with immune cells with the tumor microenvironment, which is a critical barrier to control both local and systemic disease. The composition and pattern of the immune infiltrate associates with the likelihood of response to immunotherapy. Inflamed tumors that exhibit a brisk immune cell infiltrate are responsive, while those in which immune cells are completely or partially excluded are not. Transforming growth factor β (TGFβ) is immunosuppressive and associated with the immune excluded phenotype.MethodsUsing an immune competent mammary tumor derived transplant (mTDT) model recently developed in our lab, exhibits inflamed, excluded or deserts immune infiltrate phenotypes based on localization of CD8 lymphocytes. Using whole transcriptome deep sequencing, cytof, and PET-CT imaging, we evaluated the tumor, microenvironment, and immune pathway activation among immune infiltrate phenotypes.ResultsThree distinct inflamed tumors phenotypes were identified: ‘classically’ inflamed characterized by pathway evidence of increased CD8+ T cells and decreased PD-L1 expression, inflamed tumors with pathways indicative of neovascularization and STAT3 signaling and reduced T cell mobilization, and an inflamed tumor with increased immunosuppressive myeloid phenotypes. Excluded tumors were characterized by TGFβ gene expression and pro-inflammatory cytokine signaling (e.g. TNFα, IL1β), associated with decreased leukocytes homing and increased immune cell death of cells. We visualized and quantified TGFβ activity using PET-CT imaging of 89Zr-fresolimumab, a TGFβ neutralizing antibody. TGFβ activity was significantly increased in excluded tumors compared to inflamed or desert tumors, which was supported by quantitative pathology (Perkin Elmer) of its canonical signaling target, phosphorylated SMAD2 (pSMAD2). pSMAD2 was positively correlated with PD-L1 expression in the stroma of excluded tumors. In contrast, in inflamed tumors, TGFβ activity positively correlated with increased F4/80 positive macrophages and negatively correlated with expression of PD-L1. CyTOF analysis of tumor and spleen immune phenotypes revealed increased trafficking of myeloid cells in mice bearing inflamed tumors compared to excluded and deserts.ConclusionsThe immunocompetent mTDT provides a model that bridges the gap between the immune landscape and tumor microenvironment. Integration of these high-dimensional data with further studies of response to immunotherapies will help to identify tumor features that favor response to treatment or the means to convert those that are unresponsive.

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