Immune cell phenotyping of clear cell renal cell carcinoma.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 511-511 ◽  
Author(s):  
Mazyar Ghanaat ◽  
Ming Liu ◽  
Brandon Manley ◽  
Mahyar Kashan ◽  
Maria Becerra ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
T Cell ◽  
Cell Carcinoma ◽  
Metastatic Disease ◽  
Renal Cell ◽  
Immune Cell ◽  
Clear Cell ◽  
Cell Populations ◽  
Cell Renal Cell Carcinoma ◽  
Immune Exclusion

511 Background: Clear cell renal cell carcinoma (ccRCC) tumors develop mechanisms that impair function and/or prevent entry of the host infiltrating immune cells (immune exclusion) within the tumor microenvironment. The goal of immunotherapy is to overcome this immune resistance. We aim to characterize the T−cell populations in a cohort of largely untreated high risk patients with ccRCC. Methods: We prospectively collected ccRCC tumor and adjacent normal kidney (NK) from patients undergoing surgical resection at our institution from 6/2015-8/2016. Immune cell phenotyping was performed by immune cell staining of single cell suspensions. Analysis of immune cell populations were determined by CD45+ staining and corresponding proportions of different T−cell populations (CD3+, CD4+, CD4+Treg, and CD8+ T cells). Staining for CD4+Treg was not available for two patients. Student t−test was utilized to compare the immune populations between tumor and adjacent NK tissue. Analysis was also conducted by stratifying patients who presented with localized versus metastatic disease. Results: A total of 31 tumor and adjacent NK were analyzed. Median tumor pathological size was 8.5cm (2.9cm−18cm), 27(87%) had pT3a−pT3b and 13(42%) presented with metastatic disease. Overall 84% of tumors had higher immune infiltrate with an average ratio of four-fold increase compared to adjacent NK as determined by CD45+ cells. Intriguingly, the other 16% presented with metastatic (4) or rapidly metastatic disease (1). Orthogonal validation with inferred immune populations using RNAseq data from the The Cancer Genome Atlas (TCGA) demonstrated similar aggressive behavior in tumors with lower immune infiltrate compared to NK. Comparison of immune cell populations of tumor and NK tissue is shown in table 1. No specific T-cell subtype was associated with specific clinical outcomes in this cohort. Conclusions: Our data shows a general trend of immune infiltration in ccRCC when compared to adjacent NK with a diversity of T-cell subsets and possible evidence of immune exclusion. Further genomic characterization of these tumors is currently underway. [Table: see text]

scholarly journals Extracellular Vesicles Enriched in hsa-miR-301a-3p and hsa-miR-1293 Dynamics in Clear Cell Renal Cell Carcinoma Patients: Potential Biomarkers of Metastatic Disease

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1450 ◽  
Author(s):  
Francisca Dias ◽  
Ana Luísa Teixeira ◽  
Inês Nogueira ◽  
Mariana Morais ◽  
Joana Maia ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Disease ◽  
Renal Cell ◽  
Clear Cell ◽  
Epigenetic Mechanism ◽  
Mirna Profile ◽  
Cell Renal Cell Carcinoma ◽  
Localized Disease ◽  
Potential Biomarkers

Clear cell renal cell carcinoma (ccRCC) is the most aggressive subtype of kidney cancer and up to 40% of patients submitted to surgery with a curative intent will relapse. Thus, the aim of this study was to analyze the applicability of an Extracellular vesicle (EV) derived miRNA profile as potential prognosis biomarkers in ccRCC patients. We analyzed a nine-miRNA profile in plasma EVs from 32 ccRCC patients with localized disease (before and after surgery) and in 37 patients with metastatic disease. We observed that the levels of EV-derived hsa-miR-25-3p, hsa-miR-126-5p, hsa-miR-200c-3p, and hsa-miR-301a-3p decreased after surgery, whereas hsa-miR-1293 EV-levels increased. Furthermore, metastatic patients presented higher levels of hsa-miR-301a-3p and lower levels of hsa-miR-1293 when compared to patients with localized disease after surgery. Functional enrichment analysis of the targets of the four miRNAs that decreased after surgery resulted in an enrichment of terms related to cell cycle, proliferation, and metabolism, suggesting that EV-miRNA enrichment in the presence of the tumor could represent an epigenetic mechanism to sustain tumor development. Taken together, these results suggest that EVs content varies depending on the presence or absence of the disease and that an increase of EV-derived hsa-miR-301a-3p, and decrease of EV-derived hsa-miR-1293, may be potential biomarkers of metastatic ccRCC.

scholarly journals Identification and validation of dichotomous immune subtypes based on intratumoral immune cells infiltration in clear cell renal cell carcinoma patients

2020 ◽  
Vol 8 (1) ◽  
pp. e000447
Author(s):  
Ying Xiong ◽  
Zewei Wang ◽  
Quan Zhou ◽  
Han Zeng ◽  
Hongyu Zhang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Treatment Response ◽  
Immune Cells ◽  
Renal Cell ◽  
Immune Cell ◽  
Clear Cell ◽  
Biological Pathways ◽  
Cell Renal Cell Carcinoma ◽  
Free Survival

BackgroundIncreasing evidence has elucidated the clinical significance of tumor infiltrating immune cells in predicting outcomes and therapeutic efficacy. In this study, we comprehensively analyze the tumor microenvironment (TME) immune cell infiltrations in clear cell renal cell carcinoma (ccRCC) and correlated the infiltration patterns with anti-tumor immunity and clinical outcomes.MethodsWe analyzed immune cell infiltrations in four independent cohorts, including the KIRC cohort of 533 patients, the Zhongshan ccRCC cohorts of 259 patients, the Zhongshan fresh tumor sample cohorts of 20 patients and the Zhongshan metastatic ccRCC cohorts of 87 patients. Intrinsic patterns of immune cell infiltrations were evaluated for associations with clinicopathological characteristics, underlying biological pathways, genetic changes, oncological outcomes and treatment responses.ResultsUnsupervised clustering of tumor infiltrating immune cells identified two microenvironment subtypes, TMEcluster-A and TMEcluster-B. Gene markers and biological pathways referring to immune evasion were upregulated in TMEcluster-B. TMEcluster-B associated with poor overall survival (p<0.001; HR 2.629) and recurrence free survival (p=0.012; HR 1.870) in ccRCC validation cohort. TMEcluster-B cases had worse treatment response (p=0.009), overall survival (p<0.001; HR 2.223) and progression free survival (p=0.015; HR 2.7762) in metastatic ccRCC cohort. The predictive accuracy of International Metastatic Database Consortium risk score was improved after incorporation of TME clusters.ConclusionsTMEcluster-A featured increased mast cells infiltration, prolonged survival and better treatment response. TMEcluster-B was a heavily infiltrated but immunosuppressed phenotype enriched for macrophages, CD4+T cells, Tregs, CD8+T cells and B cells. TMEcluster-B predicted dismal survival and worse treatment response in clear cell renal cell carcinoma patients.

MP5-09 CLEAR CELL RENAL CELL CARCINOMA: SOCIOECONOMIC PREDICTORS OF METASTATIC DISEASE AT DIAGNOSIS

2015 ◽  
Vol 193 (4S) ◽  
Author(s):  
Zachary Klaassen ◽  
John M. DiBianco ◽  
Rita P. Jen ◽  
Lael Reinstatler ◽  
Austin J. Evans ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Disease ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

scholarly journals Outcome of papillary versus clear cell renal cell carcinoma varies significantly in non-metastatic disease

PLoS ONE ◽  
2017 ◽  
Vol 12 (9) ◽  
pp. e0184173 ◽  
Author(s):  
Nina Wagener ◽  
Dominic Edelmann ◽  
Axel Benner ◽  
Richard Zigeuner ◽  
Hendrik Borgmann ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Disease ◽  
Renal Cell ◽  
Clear Cell ◽  
Cell Renal Cell Carcinoma

scholarly journals Transcriptome Profiling Reveals B-Lineage Cells Contribute to the Poor Prognosis and Metastasis of Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Fafen Yang ◽  
Jingjie Zhao ◽  
Xiuzhuang Luo ◽  
Tong Li ◽  
Zechen Wang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
B Cell ◽  
Cell Carcinoma ◽  
Distant Metastasis ◽  
Renal Cell ◽  
Poor Prognosis ◽  
Immune Cell ◽  
Clear Cell ◽  
Immune Therapy ◽  
Cell Renal Cell Carcinoma

Although immune therapy can improve the treatment of clear cell renal cell carcinoma (ccRCC) significantly, there are still a large proportion of ccRCC patients who progress to metastasis. Targeting the pro-metastatic immune cell in the ccRCC microenvironment could provide a solution to this problem. In this study, B cells in ccRCC biopsies were identified by using scRNA-seq and flow cytometry. The findings indicated the presence of a pro-metastatic B cell type which could be further classified into 3 subpopulations, MARCH3, B2M and DTWD1, based on their large-scaled genetic profiles, rather than traditional Immature/Mature ones. Although all of the 3 subpopulations appeared to contribute to distant metastasis, B cell (B2M) was deemed to be the most essential. Moreover, STX16, CLASRP, ATIC, ACIN1 and SEMA4B, were genes found to be commonly up-regulated in the 3 subpopulations and this was correlated to a poor prognosis of ccRCC. Furthermore, the heterogeneity of plasma cells in ccRCC was also found to contribute to metastasis of the disease. This study offers potential novel therapeutic targets against distant metastasis of cancers, and can help to improve the therapeutic efficiency of ccRCC patients.

scholarly journals Integrative Bioinformatics Analysis Demonstrates the Prognostic Value of Chromatin Accessibility Biomarkers in Clear Cell Renal Cell Carcinoma

2021 ◽  
Vol 11 ◽  
Author(s):  
Meng Meng ◽  
Tianjun Lan ◽  
Duanqing Tian ◽  
Zeman Qin ◽  
Yu Li ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Molecular Mechanisms ◽  
Proportional Hazards Model ◽  
Immune Cell ◽  
Clear Cell ◽  
Expression Profiles ◽  
Chromatin Accessibility ◽  
Cell Renal Cell Carcinoma

Clear cell renal cell carcinoma (ccRCC) accounts for 75%–85% of renal cell carcinoma (RCC) and has a poor 5-year survival rate. In recent years, medical advancement has promoted the understanding of the histopathological and molecular characterization of ccRCC; however, the carcinogenesis and molecular mechanisms of ccRCC remain unclear. Chromatin accessibility is an essential determinant of cellular phenotype. This study aimed to explore the potential role of chromatin accessibility in the development and progression of ccRCC. By the combination of open-access genome-wide chromatin accessibility profiles and gene expression profiles in ccRCC, we obtained a total of 13,474 crucial peaks, corresponding to 5,120 crucial genes and 9,185 differentially expressed genes. Moreover, two potential function modules (P2 and G4) that contained 129 upregulated genes were identified via the weighted gene co-expression network analysis (WGCNA). Furthermore, we obtained five independent predictors (FSCN1, SLC17A9, ANKRD13B, ADCY2, and MAPT), and a prognostic model was established based on these genes through the least absolute shrinkage and selection operator-proportional hazards model (LASSO-Cox) analysis. This model can stratify the ccRCC samples into a high-risk and a low-risk group, from which the patients have distinct prognosis. Further analysis demonstrated a completely different immune cell infiltration pattern between these two risk groups. This study also suggested that mast cell resting is associated with the prognosis of ccRCC and could be a target of immunotherapy. Overall, this study indicated that chromatin accessibility plays an essential role in ccRCC. The five prognostic chromatin accessibility biomarkers and the prognostic immune cells can provide a new direction for the treatment of ccRCC.

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