{
  "abstract": "Background Bladder cancer is unique among visceral malignancies in that urine, which can be easily obtained, has prolonged contact with bladder tumors. Urinary biomarkers offer the potential to provide insight into the host and tumor immune microenvironment to guide therapeutic strategies. We evaluated the immune cellular composition of urine (urine-derived lymphocytes (UDLs)) versus tumor (tumor-infiltrating lymphocytes (TILs)).Methods We employed high-dimensional flow cytometry analyses on immune cells from tumors (TILs), urine (UDLs), and peripheral blood (peripheral blood mononuclear cells) among patients with bladder cancer. We performed multiplexed immunofluorescence (mIF) of matched tumors to provide spatial context to our findings, comparing deep/invasive and superficial/urine-facing regions of matched tumors.Results Our findings suggest that the CD4 + and CD8+ T cell subsets of UDLs characterized by flow cytometry had similar phenotypic profiles to those found in TILs (cell clusters quantified by multidimensional scaling and differentiation states). Results of mIF imaging with a panel of phenotypic and functional T cell markers suggested that UDLs reflected TILs in both superficial and deep tumor sections. We also found sex-dependent patterns in TILs and UDLs, indicating the male bladder cancer tumor microenvironment is enriched in exhausted CD4+ and CD8+ T cells, while the female bladder cancer microenvironment is enriched for activated T cells.Conclusions Assessment of UDLs opens avenues of non-invasive biomarker development in clinical settings where bladder cancer TILs are hypothesized to predict clinical response. UDLs may also reflect sex-based differences in antitumor immunity.",
  "authors": [
    {
      "affiliations": [
        "Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA",
        "Roche Diagnostics Solutions, Oro Valley, Arizona, USA",
        "Pelotonia Institute for Immuno-Oncology, The Ohio State University, Columbus, Ohio, USA"
      ],
      "name": "Johanna M Schafer"
    },
    {
      "affiliations": [
        "Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA",
        "Pelotonia Institute for Immuno-Oncology, The Ohio State University, Columbus, Ohio, USA"
      ],
      "name": "No-Joon Song"
    },
    {
      "affiliations": [
        "Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA",
        "Pelotonia Institute for Immuno-Oncology, The Ohio State University, Columbus, Ohio, USA"
      ],
      "name": "Tong Xiao"
    },
    {
      "affiliations": [
        "Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA",
        "Pelotonia Institute for Immuno-Oncology, The Ohio State University, Columbus, Ohio, USA",
        "Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA"
      ],
      "name": "Timothy D Gauntner"
    },
    {
      "affiliations": [
        "Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA",
        "Department of Computer Science, The Ohio State University, Columbus, Ohio, USA"
      ],
      "name": "Kyeong Joo Jung"
    },
    {
      "affiliations": [
        "Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA"
      ],
      "name": "Emily G Fitts"
    },
    {
      "affiliations": [
        "Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA"
      ],
      "name": "Krishan Kumar"
    },
    {
      "affiliations": [
        "Department of Computer Science, The Ohio State University, Columbus, Ohio, USA",
        "University of Houston, Houston, Texas, USA"
      ],
      "name": "Hyeong Seon Jeon"
    },
    {
      "affiliations": [
        "The Ohio State University, Columbus, Ohio, USA"
      ],
      "name": "Ryan A Elaoud"
    },
    {
      "affiliations": [
        "Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA"
      ],
      "name": "Kelsi Reynolds"
    },
    {
      "affiliations": [
        "Convergent Genomics Inc, South San Francisco, California, USA"
      ],
      "name": "Vincent M Caruso"
    },
    {
      "affiliations": [
        "Convergent Genomics Inc, South San Francisco, California, USA"
      ],
      "name": "Trevor G Levin"
    },
    {
      "affiliations": [
        "Johns Hopkins Medicine, Baltimore, Maryland, USA"
      ],
      "name": "David McConkey"
    },
    {
      "affiliations": [
        "Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA",
        "Department of Urology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA"
      ],
      "name": "Cheryl T Lee"
    },
    {
      "affiliations": [
        "Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA",
        "Department of Urology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA"
      ],
      "name": "Kamal S Pohar"
    },
    {
      "affiliations": [
        "Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA",
        "Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA"
      ],
      "name": "Steven K Clinton"
    },
    {
      "affiliations": [
        "Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA",
        "Pelotonia Institute for Immuno-Oncology, The Ohio State University, Columbus, Ohio, USA",
        "Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA"
      ],
      "name": "William Carson"
    },
    {
      "affiliations": [
        "Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA",
        "Pelotonia Institute for Immuno-Oncology, The Ohio State University, Columbus, Ohio, USA",
        "Department of Biomedical Informatics, The Ohio State University College of Medicine, Columbus, Ohio, USA"
      ],
      "name": "Dongjun Chung"
    },
    {
      "affiliations": [
        "Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA",
        "Pelotonia Institute for Immuno-Oncology, The Ohio State University, Columbus, Ohio, USA",
        "Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA"
      ],
      "name": "Zihai Li"
    },
    {
      "affiliations": [
        "Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA",
        "Pelotonia Institute for Immuno-Oncology, The Ohio State University, Columbus, Ohio, USA",
        "Department of Urology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA"
      ],
      "name": "Debasish Sundi"
    }
  ],
  "title": "T cell subsets of urine-derived lymphocytes (UDLs) serve as an indicator of TILs and reflect immunological sex differences in bladder cancer",
  "uid": "52e293b5-6842-54ce-9bae-ef3bc79ef8b1"
}