{
  "abstract": "Background Renal cell carcinoma (RCC), a malignancy arising from renal tubular epithelial cells, represents 2–3% of global cancer diagnoses and 85% of all kidney neoplasms with the most common histological subtype being clear cell renal cell carcinoma (ccRCC), an immunologically and histologically diverse tumor which is associated with a poor clinical outcome. While significant progress has been made in the development of immunotherapy for ccRCC, there are still many unanswered questions about the mechanisms of immune evasion and resistance, and the development of predictive biomarkers for optimal treatment strategies for individual patients. Emerging evidence suggests that metabolic reprogramming characterized by dynamic shifts in nutrient utilization that transcend canonical Warburg physiology to encompass lipid anabolism, nutrient capture and catabolic pathways and microenvironment-driven metabolic plasticity, is key to overall ccRCC pathogenesis. This orchestrated rewiring of cellular dynamics has been suggested to sustain tumor proliferation under hypoxia while fostering immunosuppression through metabolite-mediated T cell exhaustion and potentially the presence of tumor associated macrophages (TAMs).Methods To investigate the complex interplay between the immunogenic nature of ccRCC tumors and metabolic reprogramming, we performed both gene expression and spatial proteomic profiling of 16 ccRCC patient samples representative across all clinical TNM stages (Stages I-IV) to define the changes in metabolic processes and infiltrating immune cells correlated with advancing disease. Specifically, we incorporated the new PaletrraTM end to end spatial workflow (NeoGenomics Laboratories, Inc.) and developed a panel that includes: CD3, CD4, CD8, FoxP3, CD68, CD80, CD163, CD206, CA9, CD31, LAG3, PD1, PanCK. We also included analysis using the analytically validated NanoString nCounter® Metabolic Pathways Panel to investigate metabolic reprogramming, cellular stress, and the relationship to the composition of the TME in advancing disease progression in ccRCC.Results and Conclusions We identified significant changes associated with the TME, especially immunosuppressive immune cells in advanced ccRCC disease, coupled to the identification of several metabolism-related genes that correlated with immune infiltrates in ccRCC. Identifying and understanding these metabolic alterations within the different staging of RCC will help in designing new targeted therapies and improving diagnostic tools to better care for patients with this disease.",
  "authors": [
    {
      "affiliations": [
        "NeoGenomics Laboratories, Houston, TX, USA"
      ],
      "name": "Kirsteen Maclean"
    },
    {
      "affiliations": [
        "NeoGenomics Laboratories, Houston, TX, USA"
      ],
      "name": "Lakshmi Chandramohan"
    },
    {
      "affiliations": [
        "NeoGenomics Laboratories, Aliso Viejo, CA, USA"
      ],
      "name": "Courtney Todorov"
    },
    {
      "affiliations": [
        "NeoGenomics Laboratories, Aliso Viejo, CA, USA"
      ],
      "name": "Jiong Fei"
    },
    {
      "affiliations": [
        "NeoGenomics Laboratories, Houston, TX, USA"
      ],
      "name": "Sergio Hernandez"
    },
    {
      "affiliations": [
        "NeoGenomics Laboratories, Houston, TX, USA"
      ],
      "name": "Brigitte Lovell"
    },
    {
      "affiliations": [
        "NeoGenomics Laboratories, Houston, TX, USA"
      ],
      "name": "Lisa Duncan"
    },
    {
      "affiliations": [
        "NeoGenomics Laboratories, Aliso Viejo, CA, USA"
      ],
      "name": "Judy Kuo"
    },
    {
      "affiliations": [
        "NeoGenomics Laboratories, Aliso Viejo, CA, USA"
      ],
      "name": "Marianne Thio"
    },
    {
      "affiliations": [
        "NeoGenomics Laboratories, Aliso Viejo, CA, USA"
      ],
      "name": "Eric Leones"
    },
    {
      "affiliations": [
        "NeoGenomics Laboratories, Aliso Viejo, CA, USA"
      ],
      "name": "Erinn A Parnell"
    },
    {
      "affiliations": [
        "NeoGenomics Laboratories, Aliso Viejo, CA, USA"
      ],
      "name": "Anna Juncker-Jensen"
    },
    {
      "affiliations": [
        "NeoGenomics Laboratories, Aliso Viejo, CA, USA"
      ],
      "name": "Harry Nunns"
    },
    {
      "affiliations": [
        "NeoGenomics Laboratories, Aliso Viejo, CA, USA"
      ],
      "name": "Qingyan Au"
    }
  ],
  "title": "91 Metabolic reprogramming in RCC tumors contributes to a dysfunctional immune response within the tumor microenvironment and is correlated with disease progression",
  "uid": "b6e7112b-4510-5c16-847e-a331594f1bde"
}