Immune function analysis after interferon treatment in post-surgery patients with localized clear cell renal cell carcinoma

BackgroundChemokine (C-X-C motif) ligand 13 (CXCL13) was known as a selective chemotaxis for B cells, a product of follicular helper CD4+T cells (TFH) and a contributor to tertiary lymphoid structures (TLS). Although secretion and function of CXCL13 produced by TFH have been deeply explored, the immune function and prognostic significance of CXCL13 secreted by CD8+T cells still remain unrevealed. This study aims to investigate the clinical merit of CXCL13+CD8+T cells in clear cell renal cell carcinoma (ccRCC).MethodsWe analyzed prognostic value and immune contexture that associated with CXCL13+CD8+T cells infiltration level in a total of 755 patients from Zhongshan Hospital cohort (n=223) and The Cancer Genome Atlas cohort (n=532). In vitro analyses were conducted on 42 samples of resected tumor tissue from Zhongshan Hospital in order to detect the immune status of CXCL13+CD8+T cells and total CD8+T cells. Immunohistochemistry (IHC) and flow cytometry were applied to characterize immune cells and portray the tumor microenvironment (TME) in ccRCC.ResultsIntratumoral CXCL13+CD8+T cells abundance was associated with inferior overall survival and disease-free survival. CXCL13+CD8+T cells possessed higher level of immune checkpoints like programmed cell-death protein 1 (PD-1), T-cell immunoglobulin mucin 3 (Tim-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), higher Ki-67 expression and lower tumor necrosis factor α (TNF-α), interferon γ (IFN-γ) expression. Total CD8+T cells in high-level CXCL13+CD8+T cells infiltration subgroup exhibited elevated exhausted markers (PD-1, Tim-3, TIGIT) and descended activated markers (TNF-α, IFN-γ) without quantity variance. Furthermore, the abundance of intratumoral CXCL13+CD8+T cell was correlated with immunoevasive TME accompanied by increased T helper 2 cells, tumor-associated macrophages, Foxp3+ regulatory T cells, TLS and decreased natural killer cells, GZMB+ cells.ConclusionsIntratumoral CXCL13+CD8+T cells infiltration indicated inferior clinical outcome in patients with ccRCC. CXCL13+CD8+T cells possessed increased exhausted markers, decreased effector molecules and better proliferation ability. CXCL13+CD8+T cells abundance impaired total CD8+T cells’ immune function. Intratumoral CXCL13+CD8+T cells abundance was associated with immunoevasive contexture. The abundance of CXCL13+CD8+T cells was an independent prognosticator and a potential immunotherapeutic target marker for ccRCC treatment.

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Circulating microRNAs from the Molecular Mechanisms to Clinical Biomarkers: A Focus on the Clear Cell Renal Cell Carcinoma

Genes ◽

10.3390/genes12081154 ◽

2021 ◽

Vol 12 (8) ◽

pp. 1154

Author(s):

Claudia Tito ◽

Elena De Falco ◽

Paolo Rosa ◽

Alessia Iaiza ◽

Francesco Fazi ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Mirna Expression ◽

Renal Cell ◽

Molecular Mechanisms ◽

Clear Cell ◽

Transcriptional Level ◽

Cell Renal Cell Carcinoma ◽

Post Surgery ◽

Clinical Biomarkers

microRNAs (miRNAs) are emerging as relevant molecules in cancer development and progression. MiRNAs add a post-transcriptional level of control to the regulation of gene expression. The deregulation of miRNA expression results in changing the molecular circuitry in which miRNAs are involved, leading to alterations of cell fate determination. In this review, we describe the miRNAs that are emerging as innovative molecular biomarkers from liquid biopsies, not only for diagnosis, but also for post-surgery management in cancer. We focus our attention on renal cell carcinoma, in particular highlighting the crucial role of circulating miRNAs in clear cell renal cell carcinoma (ccRCC) management. In addition, the functional deregulation of miRNA expression in ccRCC is also discussed, to underline the contribution of miRNAs to ccRCC development and progression, which may be relevant for the identification and design of innovative clinical strategies against this tumor.

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Identification of Biomarkers for Prognosis and Immunotherapy in Clear Cell Renal Cell Carcinoma

10.21203/rs.3.rs-733571/v1 ◽

2021 ◽

Author(s):

Zuhu Yu ◽

Bin Lu ◽

Hong Gao ◽

Wuxing Xiang ◽

Rongfang Liang ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Correlation Analysis ◽

Cell Carcinoma ◽

Renal Cell ◽

Target Genes ◽

Clear Cell ◽

Function Analysis ◽

Disease Free Survival ◽

Cell Renal Cell Carcinoma ◽

Potential Biomarkers

Abstract Background: Clear cell renal cell carcinoma (ccRCC) is the dominating subtype of renal cancer with high malignancy and poor prognosis, accounts for the majority of kidney cancer deaths. We conducted this research to identify novel potential biomarkers for the prognosis and immunotherapy of ccRCC patients. We screened out differentially expressed genes (DEGs) between ccRCC tissues and adjacent normal tissues with 4 microarray series from GEO database and took function analysis of DEGs with GO and KEGG pathway. Then, we constructed PPI network and identified target genes with prognostic value in ccRCC, performed immunological correlation analysis of the candidate genes to seek potential biomarkers of immunotherapy in ccRCC. Results: In total, 159 up-regulated genes and 223 down-regulated genes were screened out and 11 genes including TIMP1, PCK1, HMGCS2, G6PC, FBP1, ACAA1, HADH, HAO2, TGFBI, RRM2 and SUCLG1 were found to be associated with prognoses of ccRCC patients. After further screening and verification of the mRNA and protein expression, down-regulation of PCK1, HMGCS2, and up-regulation of RRM2 were significantly correlated with poorer prognoses both in overall survival and disease free survival in ccRCC. Further immunological correlation analysis showed RRM2 expression was correlated with immune infiltration and immunological checkpoint in ccRCC.Conclusion: We identified PCK1, HMGCS2 and RRM2 as potential markers for the prognosis of ccRCC patients with bioinformatic analyses. RRM2 may plays an important role in the oncogenicity of ccRCC and is a potential target for immunotherapy of ccRCC patients.

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638: Macroscopic Tumor Necrosis is a Prognostic Indicator for Non-Metastatic Clear Cell Renal Cell Carcinoma

The Journal of Urology ◽

10.1016/s0022-5347(18)30878-4 ◽

2007 ◽

Vol 177 (4S) ◽

pp. 214-214

Author(s):

Sung Kyu Hong ◽

Byung Kyu Han ◽

In Ho Chang ◽

June Hyun Han ◽

Ji Hyung Yu ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Renal Cell ◽

Tumor Necrosis ◽

Clear Cell ◽

Prognostic Indicator ◽

Cell Renal Cell Carcinoma ◽

Macroscopic Tumor

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Abstract #1001: Extremely Aggressive Papillary Thyroid Cancer (PTC) with Widespread Metastases Including Spleen and Clear Cell Renal Cell Carcinoma (RCC) in one Patient: An Unknown Syndromic Entity or Manifestation of Familial PTC?

Endocrine Practice ◽

10.1016/s1530-891x(20)44123-0 ◽

2017 ◽

Vol 23 ◽

pp. 210

Author(s):

Shilpi Singh ◽

Anh-Thu Nguyen ◽

Robert Anderson

Keyword(s):

Renal Cell Carcinoma ◽

Thyroid Cancer ◽

Cell Carcinoma ◽

Papillary Thyroid Cancer ◽

Renal Cell ◽

Clear Cell ◽

Papillary Thyroid ◽

Cell Renal Cell Carcinoma

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Rare localization of renal cell carcinoma metastases in the paranasal sinuses and breast: a case report

Medical Visualization ◽

10.24835/1607-0763-2018-6-13-22 ◽

2019 ◽

Vol 22 (6) ◽

pp. 13-22

Author(s):

E. V. Kryaneva ◽

N. A. Rubtsova ◽

A. V. Levshakova ◽

A. I. Khalimon ◽

A. V. Leontyev ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Paranasal Sinuses ◽

Renal Cell ◽

Clinical Case ◽

Clear Cell ◽

Malignant Tumors ◽

Metastatic Potential ◽

Cell Renal Cell Carcinoma ◽

Metastatic Lesions

This article presents a clinical case demonsratinga high metastatic potential of clear cell renal cell carcinoma combined with atypical metastases to breast and paranasal sinuses. The prevalence of metastatic lesions to the breast and paranasal sinuses in various malignant tumors depending on their morphological forms is analyzed. The authors present an analysis of data published for the last 30 years. The optimal diagnostic algorithms to detect the progression of renal cell carcinoma and to evaluate the effectiveness of the treatment are considered.

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