Dataset Information

CD70 expression patterns in renal cell carcinoma.

ABSTRACT: CD70 is up-regulated in several malignancies, where it induces cytotoxic effects on B and T lymphocytes, leading to immune escape. Novel therapeutic agents targeting CD70 have entered clinical trials. We characterized expression of CD70 protein in renal cell carcinoma specimens of various histologic subtypes and assessed their prognostic value and association with clinical/pathologic variables. We used tissue microarrays containing 330 cases using a novel fluorescent immunohistochemistry-based method of Automated Quantitative Analysis of in situ protein expression. The mean expression of CD70 was almost twice as high in tumors relative to normal tissue (P < .0001). When broken into subsets, CD70 was higher in sarcomatoid and clear cell tumors (P < .0001) and was variably elevated in oncocytomas and some papillary tumors. No association was found between CD70 expression and stage or grade. High CD70 expression was associated with decreased survival on univariate analysis in the clear cell subset of renal cell carcinoma; however, it did not retain significance on multivariate analysis. Given the elevated expression of CD70 in clear cell, sarcomatoid, and some papillary tumors, our findings suggest that CD70 might be a good drug target in renal cell carcinoma. Additional studies are warranted to assess the association between expression of CD70 and response to therapy with CD70-targeting drugs in renal cell carcinoma.

SUBMITTER: Jilaveanu LB

PROVIDER: S-EPMC3374042 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CD70 expression patterns in renal cell carcinoma.

Jilaveanu Lucia B LB Sznol Joshua J Aziz Saadia A SA Duchen Dylan D Kluger Harriet M HM Camp Robert L RL

Human pathology 20120307 9

CD70 is up-regulated in several malignancies, where it induces cytotoxic effects on B and T lymphocytes, leading to immune escape. Novel therapeutic agents targeting CD70 have entered clinical trials. We characterized expression of CD70 protein in renal cell carcinoma specimens of various histologic subtypes and assessed their prognostic value and association with clinical/pathologic variables. We used tissue microarrays containing 330 cases using a novel fluorescent immunohistochemistry-based m ...[more]

PMID: 22401771

Similar Datasets

Project description:Renal cell carcinoma (RCC) accounts for the majority of cancer-related deaths worldwide. Overexpression of CD70 has been linked to advanced stages of RCC. Therefore, this study aims to develop a multiepitope vaccine targeting the overexpressed CD70 using immunoinformatics techniques. In this investigation, in silico multiepitope vaccines were constructed by linking specific CD70 protein epitopes for helper T lymphocytes and CD8+ T lymphocytes. To enhance immunogenicity, sequences of cell-penetrating peptide (CPP), penetratin (pAntp), along with the entire sequence of tumor necrosis factor-α (TNF-α), were attached to the N-terminal and C-terminal of the CD70 epitopes. Computational assessments were performed on these chimeric vaccines for antigenicity, allergenicity, peptide toxicity, population coverage, and physicochemical properties. Furthermore, refined 3D constructs were subjected to a range of analyses, encompassing structural B-cell epitope prediction and molecular docking. The chosen vaccine construct underwent diverse assessments such as molecular dynamics simulation, immune response simulation, and in silico cloning. All vaccines comprised antigenic, nontoxic, and nonallergenic epitopes, ensuring extensive global population coverage. The vaccine constructs demonstrated favorable physicochemical characteristics. The binding affinity of chimeric vaccines to the TNF receptor remained relatively stable, influenced by the alignment of vaccine components. Molecular docking and dynamics analyses predicted stable interactions between CD70-CPP-TNF and the TNF receptor, indicating potential efficacy. In silico codon optimization and cloning of the vaccine nucleic acid sequence were accomplished using the pET28a plasmid. Furthermore, this vaccine displayed the capacity to modulate humoral and cellular immune responses. Overall, the results suggest therapeutic potential for the chimeric CD70-CPP-TNF vaccine against RCC. However, validation through in vitro and in vivo experiments is necessary. This trial is registered with NCT04696731 and NCT04046445.

Dataset Information

CD70 expression patterns in renal cell carcinoma.

Publications

CD70 expression patterns in renal cell carcinoma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets