1698 THE IDENTIFICATION OF BCG RESPONSIVE BLADDER CANCER PATIENTS PRIOR TO THERAPY USING A DIAGNOSTIC STRATEGY ASSESSING OF THE TUMOR IMMUNE MICROENVIRONMENT

Abstract

You have accessJournal of UrologyBladder Cancer: Superficial (I)1 Apr 20131698 THE IDENTIFICATION OF BCG RESPONSIVE BLADDER CANCER PATIENTS PRIOR TO THERAPY USING A DIAGNOSTIC STRATEGY ASSESSING OF THE TUMOR IMMUNE MICROENVIRONMENT Rafael Nunez-Nateras, Erin Ferrigni, Cheryl Protheroe, Melissa Stanton, James Lee, and Erik Castle Rafael Nunez-NaterasRafael Nunez-Nateras Phoenix, AZ More articles by this author , Erin FerrigniErin Ferrigni Phoenix, AZ More articles by this author , Cheryl ProtheroeCheryl Protheroe Phoenix, AZ More articles by this author , Melissa StantonMelissa Stanton Phoenix, AZ More articles by this author , James LeeJames Lee Phoenix, AZ More articles by this author , and Erik CastleErik Castle Phoenix, AZ More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.3008AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Transitional cell carcinoma is the most common form of bladder cancer (∼90% of tumors) and clinical/pathology assessments have demonstrated that the pathologic subtype, carcinoma in situ (i.e., Tis), is present in ∼40% of total bladder cancers diagnosed. However, there is currently no ability at the time of initial diagnosis to identify which of these patients will respond to standard-of-care treatment, intravesical administration of Bacillus Calmette-Guerin (BCG). Thus, Tis bladder cancer patients are often treated subjectively using a “one size fits all” approach with only about a 60% success rate (i.e., tumor-free) among treated patients. The aim of the present study was is to correlate the BCG responsiveness of patients with Tis bladder cancer with measures of the tumor immune microenvironment at the time of initial diagnosis. METHODS The immune microenvironments of tumor biopsies of 20 Tis bladder cancer patients responsive to BCG therapy (BCG+) were assessed relative to biopsies derived from 18 non-responsive patients (BCG-). Each tumor immune microenvironment was determined as a function of two immunohistochemical metrics: (i) The level of tumor eosinophil infiltration as well as the extent of eosinophil degranulation (i.e. Th2 effector arm) and (ii) The relative number of tumor-infiltrating GATA-3+ (i.e., Th2-polarized) vs. T-bet+ (i.e., Th1 polarized) lymphocytes. RESULTS The bladder biopsies of “normal” subjects displayed only a nominal eosinophil infiltrate with no evidence of degranulation or infiltrating lymphocytes. In contrast, Tis bladder tumors often displayed a robust tissue eosinophilia accompanied by degranulation. The tumor immune microenvironments were decidedly Th2 polarized with >3-fold more GATA-3+ relative to T-bet+ lymphocytes. More importantly, each of these immune biomarkers had prognostic value in the evaluation of bladder cancer patients. Specifically, the data showed that the levels of each immune biomarker were statistically higher in patients subsequently shown to be BCG+ relative to BCG- subjects. In addition, an algorithm integrating these immune metrics (i.e., Th2 Signature) provided an unambiguous biomarker that stratifies bladder cancer patients prior to treatment decisions with a high degree of specificity. CONCLUSIONS The immunohistochemical assessments of the Tis immune tumor microenvironment represents a clinically-relevant screening strategy of cancer patients as to their subsequent responsiveness to the standard-of-care treatment. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e698-e699 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Rafael Nunez-Nateras Phoenix, AZ More articles by this author Erin Ferrigni Phoenix, AZ More articles by this author Cheryl Protheroe Phoenix, AZ More articles by this author Melissa Stanton Phoenix, AZ More articles by this author James Lee Phoenix, AZ More articles by this author Erik Castle Phoenix, AZ More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...