{
  "abstract": "Background CD70 is a type II transmembrane protein and a member of the tumor necrosis factor superfamily, primarily involved in immune regulation through interactions with its receptor, CD27. Aberrant CD70 expression has been reported in various hematologic malignancies and select solid tumors, making it an emerging target for immunotherapy. However, comprehensive analyses comparing CD70 expression between tumors and normal tissues to guide clinical development are limited. This study systematically evaluates CD70 expression across tumor types and corresponding normal tissues to identify malignancies with the most favorable therapeutic selectivity profile.Methods RNA sequencing data from The Cancer Genome Atlas (TCGA) encompassing 33 tumor types were analyzed to assess CD70 expression, summarized as median transcripts per million (TPM). Normal tissue expression profiles were obtained from the Human Protein Atlas (HPA) and summarized as normalized expression (NX). Tumor-to-normal expression ratios were calculated for each tumor type. High CD70 expression was defined as median CD70 TPM >5. Among 33 tumor types analyzed, detailed comparisons were performed between clear cell renal cell carcinoma (ccRCC) and representative tumors including diffuse large B-cell lymphoma (DLBCL), mesothelioma (MESO), breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), and lung squamous cell carcinoma (LUSC). Statistical comparisons were performed using the Mann-Whitney U test.Results Clear cell renal cell carcinoma (ccRCC) demonstrated the highest median CD70 expression (39.6 TPM), followed by DLBCL (22.8 TPM) and MESO (6.8 TPM). In contrast, CD70 expression was undetectable in BRCA, COAD, and LUSC (median 0.0 TPM). Normal tissue analysis revealed low CD70 expression in kidney (1.7 NX), lung (1.9 NX), colon (4.1 NX), and breast (2.2 NX), with higher expression confined to lymphoid tissues such as T-cells (23.3 NX) and spleen (11.8 NX). The tumor-to-normal expression ratio was 23.3 for ccRCC (kidney), 1.9 for DLBCL (spleen), and 3.6 for MESO (lung). In comparative analyses, CD70 expression in ccRCC was significantly higher than in MESO, BRCA, COAD, and LUSC (all p<0.001), while no significant difference was observed between ccRCC and DLBCL (p=0.24) ( table 1).Conclusions CD70 is significantly overexpressed in ccRCC relative to normal kidney tissue, with a 23-fold tumor-to-normal expression ratio, suggesting a highly favorable therapeutic window for CD70-targeted therapies. The absence of CD70 expression in common epithelial tumors further supports the selectivity of CD70-directed approaches in renal cell carcinoma.Abstract 151 Table 1CD70 expression in tumors and corresponding normal tissues with tumor-to-normal ratios",
  "authors": [
    {
      "affiliations": [
        "Sentara Albemarle Medical Center, USACS, Elizabeth City, NC, USA"
      ],
      "name": "Mobina Shrestha"
    }
  ],
  "title": "151 CD70 overexpression in clear cell renal cell carcinoma supports favorable therapeutic index for targeted immunotherapy",
  "uid": "2211c139-930f-55b0-9c84-317d6e802f8d"
}