Immunological Response to Renal Cryoablation in an In Vivo Orthotopic Renal Cell Carcinoma Murine Model

No AccessJournal of UrologyInvestigative Urology1 Jan 2010Immunological Response to Renal Cryoablation in an In Vivo Orthotopic Renal Cell Carcinoma Murine Modelis companion of800 Laparoscopic Partial Nephrectomies: A Single Surgeon SeriesRenal Insufficiency is an Independent Risk Factor for Complications After Partial Nephrectomy Surena F. Matin, Padmanee Sharma, Inderbir S. Gill, Charles Tannenbaum, Michael G. Hobart, Andrew C. Novick, and James H. Finke Surena F. MatinSurena F. Matin Department of Urology, University of Texas M. D. Anderson Cancer Center, Houston, Texas More articles by this author , Padmanee SharmaPadmanee Sharma Department of Genitourinary Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas More articles by this author , Inderbir S. GillInderbir S. Gill Department of Urology, University of Southern California, Los Angeles, California Financial interest and/or other relationship with Hansen. More articles by this author , Charles TannenbaumCharles Tannenbaum Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio More articles by this author , Michael G. HobartMichael G. Hobart Alberta Urology Institute, Edmonton, Alberta, Canada More articles by this author , Andrew C. NovickAndrew C. Novick Glickman Urological Institute, Cleveland Clinic, Cleveland, Ohio More articles by this author , and James H. FinkeJames H. Finke Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio Financial interest and/or other relationship with Pfizer. More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2009.08.110AboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract Purpose: The immunological consequences of cryoablation for renal cell carcinoma are largely unknown. Cryoablation is an attractive therapeutic option for tumors due to its minimally invasive nature. Cryoablation is also potentially immunogenic. We describe the development of an animal model to deliver in vivo renal cryotherapy to orthotopically implanted renal cell carcinoma and the results of multiple immunological interrogations after cryoablation. Materials and Methods: Four to 6-week-old female Balb/c mice (Jackson Laboratories, Bar Harbor, Maine) underwent renal subcapsular implantation of the syngeneic murine renal cell carcinoma Renca. Two weeks later contact cryoablation was done in tumor bearing kidneys. Another group of animals underwent cryoablation of normal kidneys. Animals were sacrificed 2 weeks after tumor injection or 1 and 2 weeks after cryoablation, respectively. Kidneys, spleens and draining lymph nodes were harvested. Evaluation consisted of immunohistochemistry, immunofluorescence and gene expression profiling using reverse-transcriptase polymerase chain reaction. Results: Subcapsular tumor implantation was successful in all cases and confirmed histologically. No significant lymphocytic infiltrate was seen in tumor only animals but those treated with cryoablation (tumor and nontumor bearing) had a significant inflammatory response primarily in sublethal tissue injury and perivascular areas. After cryoablation most infiltrating cells were neutrophils, macrophages and T cells. Polymerase chain reaction showed increased interferon-γ production in kidneys after cryoablation. Conclusions: This study shows the potential feasibility of this animal model for studying cryo-immunology. We confirm the absence of any significant immune cell infiltration in tumor bearing kidneys and report a significant inflammatory infiltrate after cryoablation, consisting primarily of neutrophils, macrophages, and CD4+ and CD8+ T cells with an increase in the T helper type 1/2 ratio. 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Google Scholar © 2010 by American Urological AssociationFiguresReferencesRelatedDetailsRelated articlesJournal of Urology12 Nov 2009800 Laparoscopic Partial Nephrectomies: A Single Surgeon SeriesJournal of Urology13 Nov 2009Renal Insufficiency is an Independent Risk Factor for Complications After Partial Nephrectomy Volume 183Issue 1January 2010Page: 333-338 Advertisement Copyright & Permissions© 2010 by American Urological AssociationKeywordsrenal cellcryosurgerykidneymicecarcinomaimmunologyAcknowledgmentsCarol deLaMotte assisted with immunofluorescence. Dr. Judy Drazba assisted with confocal microscopy. Drs. Daisuke Kudo and Andrew Steinberg assisted with animal experiments. Linda Vargo sectioned histological specimens. Dr. David McConkey critically reviewed the manuscript. Endocare Corp. provided cryoprobes.MetricsAuthor Information Surena F. Matin Department of Urology, University of Texas M. D. Anderson Cancer Center, Houston, Texas More articles by this author Padmanee Sharma Department of Genitourinary Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas More articles by this author Inderbir S. Gill Department of Urology, University of Southern California, Los Angeles, California Financial interest and/or other relationship with Hansen. More articles by this author Charles Tannenbaum Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio More articles by this author Michael G. Hobart Alberta Urology Institute, Edmonton, Alberta, Canada More articles by this author Andrew C. Novick Glickman Urological Institute, Cleveland Clinic, Cleveland, Ohio More articles by this author James H. Finke Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio Financial interest and/or other relationship with Pfizer. More articles by this author Expand All Advertisement PDF downloadLoading ...