Tumour necrosis factor receptor-associated factor-1 (TRAF-1) expression is increased in renal cell carcinoma patient serum but decreased in cancer tissue compared with normal: potential biomarker significance

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.

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Interleukin-6, tumour necrosis factor α and interleukin-1β in patients with renal cell carcinoma

British Journal of Cancer ◽

10.1038/sj.bjc.6600257 ◽

2002 ◽

Vol 86 (9) ◽

pp. 1396-1400 ◽

Cited By ~ 107

Author(s):

N Yoshida ◽

S Ikemoto ◽

K Narita ◽

K Sugimura ◽

S Wada ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Tumour Necrosis Factor ◽

Interleukin 6 ◽

Renal Cell ◽

Tumour Necrosis ◽

Interleukin 1Β ◽

Tumour Necrosis Factor Α ◽

Factor Α ◽

Necrosis Factor

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632: Synergistic Killing of Renal Cell Carcinoma Cells by Interferon Alpha and Tumor Necrosis Factor (TNF) Related Apoptosis Inducing Ligand (TRAIL)

The Journal of Urology ◽

10.1016/s0022-5347(18)34872-9 ◽

2005 ◽

Vol 173 (4S) ◽

pp. 172-172

Author(s):

Peter E. Clark ◽

Kenneth Gyabaah ◽

Andrew M. Thorburn

Keyword(s):

Renal Cell Carcinoma ◽

Tumor Necrosis Factor ◽

Cell Carcinoma ◽

Interferon Alpha ◽

Renal Cell ◽

Tumor Necrosis ◽

Carcinoma Cells ◽

Necrosis Factor

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CMTM6 expression as a potential biomarker for immunotherapy in metastatic renal cell carcinoma

BJU International ◽

10.1111/bju.15341 ◽

2021 ◽

Author(s):

Gennadi Tulchiner ◽

Andrea Brunner ◽

Manuela Schmidinger ◽

Nina Staudacher ◽

Jacob J. Orme ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Metastatic Renal Cell Carcinoma ◽

Renal Cell ◽

Potential Biomarker

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

Cancer Cell International ◽

10.1186/s12935-021-02039-y ◽

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.

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