scholarly journals PD-L1+ and Hyal2+ myeloid cells in renal cell carcinoma: a case report

2021 ◽  
Author(s):  
Elizabeth Kwenda ◽  
Paul R. Dominguez-Gutierrez ◽  
Padraic O’Malley ◽  
Paul L. Crispen ◽  
Sergei Kusmartsev
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Immune Suppression ◽  
Renal Cell ◽  
Tumor Tissue ◽  
Myeloid Cells ◽  
Suppressor Cells ◽  
Tumor Stroma ◽  
Renal Cell Carcinoma Patient ◽  
Cancer Tissue

AbstractRCC patients frequently have increased numbers of immunosuppressive myeloid cells in circulation. High numbers of myeloid derived suppressor cells (MDSCs) in the blood are associated with immune suppression as well as with cancer-related inflammation which drives the mobilization of myeloid cells to tumor tissue. Here we show that peripheral blood from a previously untreated renal cell carcinoma patient has increased numbers of monocytic CD33+CD11b+ MDSCs, which also co-expressed PD-L1 and membrane-bound enzyme hyaluronidase 2 (Hyal2). PD-L1 expression is associated with immune suppression, whereas expression of Hyal2 is associated with inflammation, because Hyal2+ myeloid cells can degrade the extracellular hyaluronan (HA), leading to the accumulation of pro-inflammatory HA fragments with low molecular weight. These findings implicate the potential involvement of monocytic MDSCs in both tumor-associated immune suppression and cancer-related inflammation. Analysis of organoid-like tumor-tissue slice cultures prepared from cancer tissue of the same patient revealed the significant presence of PD-L1+ HLA-DR+ macrophage-like or dendritic cell-like antigen-presenting cells in tumor stroma. Interestingly that stroma-associated PD-L1+ cells frequently have intracellular hyaluronan. Collectively, data presented in this study suggest that the interplay between tumor-recruited myeloid cells and stromal hyaluronan may contribute to the inflammation and immune tolerance in cancer.

scholarly journals Oxidative Stress Regulates Expression of VEGFR1 in Myeloid Cells: Link to Tumor-Induced Immune Suppression in Renal Cell Carcinoma

2008 ◽  
Vol 181 (1) ◽  
pp. 346-353 ◽  
Author(s):  
Sergei Kusmartsev ◽  
Evgeniy Eruslanov ◽  
Hubert Kübler ◽  
Timothy Tseng ◽  
Yoshihisa Sakai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Immune Suppression ◽  
Renal Cell ◽  
Myeloid Cells

scholarly journals Expression and content of VHL in kidney cancer tissue, relationship with clinical and morphological parameters of the disease, expression of transcriptional and growth factors

2021 ◽  
Vol 67 (5) ◽  
pp. 694-698
Author(s):  
Lyudmila Spirina ◽  
Zahar Yurmazov ◽  
Evgenii Usy`nin ◽  
Irina Kondakova
Keyword(s):  
Renal Cell Carcinoma ◽  
Growth Factors ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Tumor Tissue ◽  
Mrna Level ◽  
Cancer Tissue ◽  
Morphological Parameters ◽  
Vhl Protein ◽  
The Relationship

Introduction. The molecular picture of the development of HIF overexpression against VHL deficiency background is a key event associated with the manifestation and progression of clear cell renal cell carcinoma. However, this indicator's significance for the development of the disease and the formation of a response to targeted therapy is not clear. The study aimed to study the relationship between the expression and content of VHL in kidney cancer tissue with clinical, morphological parameters, mRNA level NF-κB p65, NF-κB p50, HIF-1, HIF-2, VEGF, and CAIX. Material and methods. The study included 39 patients with renal cell carcinoma. The disease's localized form (T1-2N0M0) was diagnosed in 20 patients; 19 patients had a disseminated process (T1-3N0-1M1). The study's material was normal, and tumor tissue was obtained during the surgical stage of treatment. VHL expression was determined by real-time PCR. The pVHL protein content was estimated using the Western Blotting method. Results. As a result of the study, it was noted that an increase in the VHL expression, together with a decrease in its protein level, was associated with an increase in tumor size. The prevalence of the disease was accompanied by an increase in both mRNA and VHL content in cancers. There was a negative correlation between the level of VHL expression, the content of the corresponding protein, and a positive association with the expression of NF-κB p65. VHL content in cancers was associated with decreased expression of NF-κB p50, NF-κB p65, and VEGF. Discussion. An increase in VHL expression in tumor tissue promoted the growth of mRNA of transcription factors, in particular NF-κB, which is accompanied by tumor spread. An increase in the VHL protein content led to the suppression of the mRNA level of transcriptional and growth factors, which is probably associated with their inactivation, including through proteasome cleavage, and is an important stage in oncogenesis. Conclusion. The relationship between the expression and content of the VHL protein is of decisive importance in the development of the disease, the formation of distant metastases.

scholarly journals Down-regulation of BCL2L13 renders poor prognosis in clear cell and papillary renal cell carcinoma

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Fei Meng ◽  
Luojin Zhang ◽  
Mingjun Zhang ◽  
Kaiqin Ye ◽  
Wei Guo ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Kidney Cancer ◽  
Renal Cell ◽  
Poor Prognosis ◽  
Clear Cell ◽  
Papillary Renal Cell Carcinoma ◽  
Functional Enrichment ◽  
Cancer Tissue ◽  
Down Regulation

Abstract Background BCL2L13 belongs to the BCL2 super family, with its protein product exhibits capacity of apoptosis-mediating in diversified cell lines. Previous studies have shown that BCL2L13 has functional consequence in several tumor types, including ALL and GBM, however, its function in kidney cancer remains as yet unclearly. Methods Multiple web-based portals were employed to analyze the effect of BCL2L13 in kidney cancer using the data from TCGA database. Functional enrichment analysis and hubs of BCL2L13 co-expressed genes in clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) were carried out on Cytoscape. Evaluation of BCL2L13 protein level was accomplished through immunohistochemistry on paraffin embedded renal cancer tissue sections. Western blotting and flow cytometry were implemented to further analyze the pro-apoptotic function of BCL2L13 in ccRCC cell line 786-0. Results BCL2L13 expression is significantly decreased in ccRCC and pRCC patients, however, mutations and copy number alterations are rarely observed. The poor prognosis of ccRCC that derived from down-regulated BCL2L13 is independent of patients’ gender or tumor grade. Furthermore, BCL2L13 only weakly correlates with the genes that mutated in kidney cancer or the genes that associated with inherited kidney cancer predisposing syndrome, while actively correlates with SLC25A4. As a downstream effector of BCL2L13 in its pro-apoptotic pathway, SLC25A4 is found as one of the hub genes that involved in the physiological function of BCL2L13 in kidney cancer tissues. Conclusions Down-regulation of BCL2L13 renders poor prognosis in ccRCC and pRCC. This disadvantageous factor is independent of any well-known kidney cancer related genes, so BCL2L13 can be used as an effective indicator for prognostic evaluation of renal cell carcinoma.

Rare anti-VEGFR therapy-induced toxicity and long-term response to immunotherapy in a rare non-clear cell renal cell carcinoma patient

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Fabio Catalano ◽  
Sara Elena Rebuzzi ◽  
Veronica Murianni ◽  
Alessandra Damassi ◽  
Valentino Martelli ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Clear Cell ◽  
Renal Cell Carcinoma Patient ◽  
Cell Renal Cell Carcinoma ◽  
Carcinoma Patient ◽  
Term Response

scholarly journals Dll4 Blockade Potentiates the Anti-Tumor Effects of VEGF Inhibition in Renal Cell Carcinoma Patient-Derived Xenografts

PLoS ONE ◽  
2014 ◽  
Vol 9 (11) ◽  
pp. e112371 ◽  
Author(s):  
Kiersten Marie Miles ◽  
Mukund Seshadri ◽  
Eric Ciamporcero ◽  
Remi Adelaiye ◽  
Bryan Gillard ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Renal Cell Carcinoma Patient ◽  
Carcinoma Patient ◽  
Vegf Inhibition

scholarly journals Arginase I–Producing Myeloid-Derived Suppressor Cells in Renal Cell Carcinoma Are a Subpopulation of Activated Granulocytes

2009 ◽  
Vol 69 (4) ◽  
pp. 1553-1560 ◽  
Author(s):  
Paulo C. Rodriguez ◽  
Marc S. Ernstoff ◽  
Claudia Hernandez ◽  
Michael Atkins ◽  
Jovanny Zabaleta ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Suppressor Cells ◽  
Myeloid Derived Suppressor Cells ◽  
Arginase I

The Significance of INHBE Expression in the Cancer Cells of Clear-Cell Renal Cell Carcinoma

2021 ◽  
pp. 1-11
Author(s):  
Zi-Bin Xu ◽  
Mei-Fu Gan ◽  
Hong-Yuan Yu ◽  
Li-Cai Mo ◽  
Yu-Hui Xia ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Cancer Cells ◽  
Renal Cell ◽  
Tumor Tissue ◽  
Transforming Growth Factor ◽  
Clear Cell ◽  
Tumor Promoter ◽  
Sequencing Data ◽  
Cell Renal Cell Carcinoma

<b><i>Background:</i></b> Activins and inhibins are structurally related dimeric glycoprotein hormones belonging to the transforming growth factor-β superfamily but whether they are also involved in malignancy is far from clear. No study has reported the expression of INHBE in kidney cancer. The purpose of this study was to examine the expressions of INHBE in the tumor tissue of patients with clear-cell renal cell carcinoma (ccRCC) and to explore the pathologic significance. <b><i>Methods:</i></b> The INHBE mRNA expression in the tumor tissue of ccRCC patients was analyzed by using RNA sequencing data from the TCGA database. To examine the expression of inhibin βE protein, 241 ccRCC patients were recruited and immunohistochemistry was performed on the tumor tissue of these patients along with 39 normal renal samples. The association between the inhibin βE expression level and patient’s clinicopathological indices was evaluated. <b><i>Results:</i></b> In the normal renal tissue, inhibin βE was found to be expressed mainly by renal tubular epithelial cells. In the tumor tissue, inhibin βE was expressed mainly in cancer cells. The expressions of INHBE mRNA and protein in the tumor tissue of ccRCC patients increased significantly compared with those in normal renal samples. There was a significant correlation between the level of inhibin βE in the tumor tissue and tumor grade. Patients with a lower inhibin βE expression in the tumor tissue were found to have a longer overall survival and disease-specific survival. <b><i>Conclusions:</i></b> INHBE might be involved in the pathogenesis of ccRCC and function as a tumor promoter.

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