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Journal of Molecular Medicine

, Volume 90, Issue 1, pp 55–66 | Cite as

Transcript signature predicts tissue NK cell content and defines renal cell carcinoma subgroups independent of TNM staging

  • Judith Eckl
  • Alexander Buchner
  • Petra U. Prinz
  • Rainer Riesenberg
  • Sabine I. Siegert
  • Robert Kammerer
  • Peter J. Nelson
  • Elfriede NoessnerEmail author
Original Paper

Abstract

Clear cell renal cell carcinoma (ccRCC) is an aggressive and difficult to manage cancer. Immunotherapy has the potential to induce long-lasting regression in a small group of patients. However, severe side effects limit broad application which highlights the need for a marker to distinguish responder from nonresponder. TNMG staging, referring to tumor size, lymph node involvement, presence of metastasis, and grade of tumor differentiation, represents an important prognostic system but is not useful for predicting responders to immunotherapy. NK cells are potent antitumor effector cells, and a role as prognostic marker in some solid tumors has been suggested. As NK cells are responsive to various immune modifiers, they may be important mediators of patient response to immunotherapies, in particular those including IL-2. We report that the NK cell percentage within RCC-infiltrating lymphocytes, as determined by flow cytometry, allows ccRCC subgrouping in NKhigh/NKlow tissues independent of TNMG classification. Quantitative reverse transcriptase polymerase chain reaction using whole-tissue RNA identified four markers (NKp46, perforin, CX3CL1, and CX3CR1) whose transcript levels reproduced the NKhigh/NKlow tissue distinction identified by flow cytometry with high selectivity and specificity. Combined in a multiplex profile and analyzed using neural network, the accuracy of predicting the NKhigh/NKlow groups was 87.8%, surpassing that of each single marker. The tissue transcript signature, based on a robust high-throughput methodology, is easily amenable to archive material and clinical translation. This now allows the analysis of large patient cohorts to substantiate a role of NK cells in cancer progression or response to immunotherapy.

Keywords

NK cells Transcript signature Renal cell carcinoma Prognosis Immunotherapy 

Notes

Acknowledgments

We thank A. Brandl, A. Mojaat, and A. Wechselberger for the excellent technical assistance and R. Oberneder (Urology Clinic Dr. Castringius, Munich-Planegg, Germany) for the help with the tissue collection. Financial support for this research was given by grants from the Deutsche Forschungsgemeinschaft, Sonderforschungsbereich Transregio SFB-TR36 (P.J. Nelson, E. Noessner) and Sonderforschungsbereich SFB455 (E. Noessner) and a grant from the European Union EU P6 “INNOCHEM” (P.J. Nelson).

Conflicts of interest

The authors declare no conflicts of interest.

Supplementary material

109_2011_806_MOESM1_ESM.doc (216 kb)
ESM 1 DOC 215 kb

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Judith Eckl
    • 1
  • Alexander Buchner
    • 2
    • 3
  • Petra U. Prinz
    • 7
  • Rainer Riesenberg
    • 2
  • Sabine I. Siegert
    • 4
  • Robert Kammerer
    • 5
  • Peter J. Nelson
    • 6
  • Elfriede Noessner
    • 7
    Email author
  1. 1.Clinical Cooperation Group “Immune Monitoring”, Institute of Molecular Immunology, Helmholtz Zentrum München—German Research Center for Environmental HealthMunichGermany
  2. 2.Tumor Immunology Laboratory, LIFE CenterMunichGermany
  3. 3.Department of UrologyUniversity Clinic GrosshadernMunichGermany
  4. 4.Institute of PathologyLudwig-Maximilians-UniversityMunichGermany
  5. 5.Institute of ImmunologyFriedrich-Loeffler-InstitutTübingenGermany
  6. 6.Clinical Biochemistry, Medical PoliclinicLudwig Maximilians University MunichMunichGermany
  7. 7.Institute of Molecular Immunology, Helmholtz Zentrum München—German Research Center for Environmental HealthMunichGermany

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