The Effect of CD86 Expression on the Proliferation and the Survival of CLL Cells

Takács, Ferenc; Tolnai-Kriston, C.; Hernádfői, Márk; Szabó, Orsolya; Szalóki, Gábor; Szepesi, Ágota; Czeti, Ágnes; Matolcsy, András; Barna, Gábor

doi:10.1007/s12253-018-0512-7

Cited by 10 publications

(15 citation statements)

References 17 publications

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“…Although CD86 has been reported to be associated with poor prognosis in chronic lymphocytic leukemia (9), myeloma (29), and overall glioma (30), there was no report of its prognostic value in LGG and melanoma. As shown in the present study, CD86 expression level was significantly correlated with worse survival and it was upregulated as the tumor grade increases in LGG.…”

Section: Discussionmentioning

confidence: 99%

“…CD86 (B7-2), an immunoglobulin-like protein on antigen presenting cells (APCs), works in parallel with the CD80 (B7-1) as a natural ligand for CD28 and CTLA-4 (9). CD86 promotes T-cell proliferation, function and survival by interacting with CD28 as a co-stimulator, while in activated T cells it interacts with CTLA-4 and acts as a suppressor (10,11).…”

Section: Introductionmentioning

confidence: 99%

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Integrated Analysis Reveals Prognostic Value and Immune Correlates of CD86 Expression in Lower Grade Glioma

Qiu

Tian

et al. 2021

Front. Oncol.

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BackgroundCD86 has great potential to be a new target of immunotherapy by regulating cancer immune response. However, it remains unclear whether CD86 is a friend or foe in lower-grade glioma (LGG).MethodsThe prognostic value of CD86 expression in pan-cancer was analyzed using Cox regression and Kaplan-Meier analysis with data from the cancer genome atlas (TCGA). Cancer types where CD86 showed prognostic value in overall survival and disease-specific survival were identified for further analyses. The Chinese Glioma Genome Atlas (CGGA) dataset were utilized for external validation. Quantitative real-time PCR (qRT-PCR), Western blot (WB), and Immunohistochemistry (IHC) were conducted for further validation using surgical samples from Jiangsu Province hospital. The correlations between CD86 expression and tumor immunity were analyzed using the Estimation of Stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm, Tumor IMmune Estimation Resource (TIMER) database, and expressions of immune checkpoint molecules. Gene Set Enrichment Analysis (GSEA) was performed using clusterprofiler r package to reveal potential pathways.ResultsPan-cancer survival analysis established CD86 expression as an unfavorable prognostic factor in tumor progression and survival for LGG. CD86 expression between Grade-II and Grade-III LGG was validated using qRT-PCR and WB. Additionally, CD86 expression in LGG with unmethylated O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter was significantly higher than those with methylated MGMT (P<0.05), while in LGG with codeletion of 1p/19q it was significantly downregulated as opposed to those with non-codeletion (P<2.2*10-16). IHC staining validated that CD86 expression was correlated with MGMT status and X1p/19q subtypes, which was independent of tumor grade. Multivariate regression validated that CD86 expression acts as an unfavorable prognostic factor independent of clinicopathological factors in overall survival of LGG patients. Analysis of tumor immunity and GSEA revealed pivotal role of CD86 in immune response for LGG.ConclusionsIntegrated analysis shows that CD86 is an unfavorable prognostic biomarker in LGG patients. Targeting CD86 may become a novel approach for immunotherapy of LGG.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Integrated Analysis Reveals Prognostic Value and Immune Correlates of CD86 Expression in Lower Grade Glioma

Qiu

Tian

et al. 2021

Front. Oncol.

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“…Expression of CD86 on CLL cells is signi cantly lower than on non-tumor B-cells [33], and its expression increased on activated B-cells [34] suggesting that CD86 could be a marker for the activation of CLL cells [35,36]. The expression of CD86 may have a prognostic impact on CLL, because the increased expression of CD86 is associated with worse prognosis [18,37]. According to Herman et al the expression of CD86 is decreased during ibrutinib treatment [31].…”

Section: Discussionmentioning

confidence: 99%

“…in bone marrow (BM) or in the lymph nodes (LN)) in clinical setting, it would be useful to nd markers on which expression on CLL cells in peripheral blood could predict the progression of the disease in their microenvironment as well. Considering this lack of scienti c experience, in this study we aimed to examine further markers on peripheral blood CLL cells that play important roles in the pathogenesis of CLL (CD69, CD184, CD27, CD185, CD86) by ow cytometry [13][14][15][16][17][18]. Moreover, we examined whether the expression of these markers correlates with ibrutinib treatment or resistance.…”

Section: Introductionmentioning

confidence: 99%

Detection of emerging ibrutinib resistance by flow cytometry in patients with chronic lymphocytic leukemia

Takács

Kotmayer

Czeti

et al. 2021

Preprint

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Background: Bruton ’ s tyrosine kinase inhibitor ibrutinib has revolutionized the treatment of chronic lymphocytic leukemia (CLL). Although ibrutinib is a highly effective drug, continuous treatment is required to maintain remission, which may lead to acquired ibrutinib resistance. Early detection of acquired resistance preceding clinical disease progression is an important issue. This is why our aim was to investigate several phenotypic markers on CLL cells to reveal changes in their expression during ibrutinib treatment in sensitive and clinically resistant patients. Materials and methods: In our study 28 (treatment naive, ibrutinib sensitive, clinically ibrutinib resistant) peripheral blood (PB), and 6 paired PB and bone marrow (BM) samples from CLL patients were examined. The expression of several surface markers (CD69, CD184, CD86, CD185, CD27) was assessed by flow cytometry in each sample. Furthermore, the presence of the BTK C481S resistance mutation was tested using digital droplet PCR (ddPCR) in samples from ibrutinib sensitive and resistant cases. In addition, we investigated the changes of CLL cells ’ phenotype during ibrutinib treatment in one patient with acquired ibrutinib resistance. Results: We found that the expression of CD27 decreased during ibrutinib therapy but increased again at the onset of clinical resistance. Expressions of CD69 and CD86 were also elevated at the onset of clinical ibrutinib resistance. Furthermore, the expression of CD86 showed correlation between PB and BM samples. Relapsed cases with high CD86 expression were positive for BTK C481S mutation. In addition, our prospective study showed that the increases in the expression of CD27, CD69 and CD86 were detectable up to several months before the onset of clinical resistance. Conclusion: Our research suggests that the flow cytometric measurements of certain markers, especially CD86, may predict development of ibrutinib resistance, however, confirmatory experiments are still required. Monitoring CD86 expression on peripheral blood CLL cells during ibrutinib treatment may become a potential new method to detect acquired ibrutinib resistance in the near future.

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“…It is widely known that the CD86 molecule (B7-2) belongs to the B-7 family. Together with CD80 molecule (B7-1), it is expressed on antigen-presenting cells(APCs, like dendritic cells, macrophages, and B-cells) [35]. Diseases related to CD86 include acute myocarditis and myocarditis.…”

Section: Discussionmentioning

confidence: 99%

Identification of key genes related to macrophage infiltration in gastric cancer based on WGCNA

Chen¹,

Zhang

Cao

et al. 2020

Preprint

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Background: Gastric cancer (GC) is rampant around the world. Most of the GC cases are detected in advanced stages with poor prognosis. The identification of marker genes for early diagnosis is of great significance. Studying the tumor environment is helpful to acknowledge the process of tumorigenesis, development, and metastasis.Methods: In GEO, 22 kinds of immune cell infiltration were calculated by CIBERSORT. Macrophages were discovered remarkably infiltrated higher in GC compared with normal tissues. WGCNA was utilized to construct the network and then identify key modules and genes related to macrophages in TCGA.Results: Finally, 18 hub genes were verified. In the PPI bar chart, the top 3 genes were chosen as hub genes involved in most pathways. On the TIMER and THPA websites, it is verified that the expression levels of CYBB, CD86 and C3AR1 genes in tumor tissues were higher than those in normal tissues.Conclusion: These genes may work as biomarkers or targets for accurate diagnosis and treatment of GC in the future. Our findings may be a new strategy for the treatment of GC.

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The Effect of CD86 Expression on the Proliferation and the Survival of CLL Cells

Cited by 10 publications

References 17 publications

Integrated Analysis Reveals Prognostic Value and Immune Correlates of CD86 Expression in Lower Grade Glioma

Integrated Analysis Reveals Prognostic Value and Immune Correlates of CD86 Expression in Lower Grade Glioma

Detection of emerging ibrutinib resistance by flow cytometry in patients with chronic lymphocytic leukemia

Identification of key genes related to macrophage infiltration in gastric cancer based on WGCNA

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