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The prognostic effect of immunoscore in patients with clear cell renal cell carcinoma: preliminary results

  • Ismail SelviEmail author
  • Umut Demirci
  • Nazan Bozdogan
  • Halil Basar
Urology - Original Paper
  • 71 Downloads

Abstract

Purpose

This study aimed to evaluate the density of CD8+ and CD3+ tumor-infiltrating lymphocytes (TILs) and determine whether the immunoscore has any prognostic effect on the oncological outcomes in patients with clear cell renal cell carcinoma (RCC).

Materials and methods

A total of 129 patients diagnosed with clear cell RCC following radical or partial nephrectomy between 2009 and 2014 were retrospectively analyzed. Both tumor core (CT) and the invasive margin of nephrectomy specimens were assessed. The specimens were immunostained for anti-CD8+ and anti-CD3+ TILs. The patients were divided into three groups (favorable, intermediate, and poor risk) according to immunoscore levels.

Results

In the multivariate analysis, a favorable immunoscore (I3–4) was associated with prolonged disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) (HR 2.652, 2.848, and 2.933, respectively; all p < 0.001). The lower Fuhrman grade and pathological tumor-node-metastasis (TNM) stage had better DFS, PFS, and OS, whereas prolonged PFS was associated with a higher density of CD8+ CT (HR 1.602, 95% CI 0.934–3.470; p = 0.014). The shorter DFS, PFS, and OS were observed in the group with poor immunoscore (I0–1) at the early TNM stage of RCC (p < 0.001). In the metastatic subgroup analysis, the immunoscore showed better estimation than the International Metastatic RCC Database Consortium model and the Memorial Sloan-Kettering Cancer Center risk model for progression and OS (p < 0.001).

Conclusion

The additional contributions of immunoscore to TNM stage, Fuhrman grade, and the WHO/ISUP 2016 grade for estimating oncological outcomes were found in ROC analysis. According to our preliminary results, immunoscore can be a promising prediction tool in clear cell RCC for postoperative oncological outcomes following nephrectomy.

Keywords

CD3+ CD8+ Clear cell renal cell carcinoma Immunoscore Oncologic outcomes Tumor-infiltrating lymphocytes 

Notes

Author contributions

IS: conception and design, acquisition of data, statistical analysis, analysis and interpretation of data, and drafting of the manuscript. UD: conception and design, and critical revision of the manuscript for important intellectual content. NB: analysis and interpretation of data, pathological evaluation, and critical revision of the manuscript for important intellectual content. HB: critical revision of the manuscript for important intellectual content.

Funding

This work is financially supported by Health Science University Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital through the scientific research fund with the decision of dated 03.11.2017 and numbered 1.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval for research involving human participants

The study was approved by the local ethics committee (the protocol number: 2018-02/18; the date of approval: February 7, 2018) at Health Science University Dr. Abdurrahman Yurtaslan Ankara Oncology Training and Research Hospital. All procedures performed in our study involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informal written informed consent was obtained from all individual participants included in the study. The data of patients who did not consent were not used.

References

  1. 1.
    Rendon RA, Kapoor A, Breau R et al (2014) Surgical management of renal cell carcinoma: Canadian Kidney Cancer Forum Consensus. Can Urol Assoc J 8:398–412CrossRefGoogle Scholar
  2. 2.
    Lipworth L, Tarone RE, McLaughlin JK (2006) The epidemiology of renal cell carcinoma. J Urol 176:2353–2358CrossRefGoogle Scholar
  3. 3.
    Ljungberg B, Albiges L, Bensalah K et al (2019) European Association of Urology guidelines on renal cell carcinoma: the 2019 update. In. ISBN 978-94-92671-04-2. EAU Guidelines Office, Arnhem, The Netherlands. ISBN 978-94-92671-04-2. http://uroweb.org/guidelines/compilations-of-all-guidelines/. Accessed 19 Mar 2019
  4. 4.
    Galon J, Pagès F, Marincola FM, Thurin M, Trinchieri G, Fox BA et al (2012) The immune score as a new possible approach for the classification of cancer. J Transl Med 10:1–4CrossRefGoogle Scholar
  5. 5.
    Galon J, Mlecnik B, Bindea G, Angell HK, Berger A, Lagorce C et al (2014) Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours. J Pathol 232:199–209CrossRefGoogle Scholar
  6. 6.
    Kim JK, Kim SH, Song MK, Joo J, Seo SI, Kwak C et al (2019) Application of the international metastatic renal cell carcinoma database consortium and memorial Sloan Kettering cancer center risk models in patients with metastatic non-clear cell renal cell carcinoma: a multi-institutional retrospective study using the korean metastatic renal cell carcinoma registry. Cancer Res Treat 51(2):758–768CrossRefGoogle Scholar
  7. 7.
    Bindea G, Mlecnik B, Angell HK, Galon J (2014) The immune landscape of human tumors implications for cancer immunotherapy. OncoImmunology 3:27456–27458CrossRefGoogle Scholar
  8. 8.
    Mlecnik B, Bindea G, Angell HK, Maby P, Angelova M, Tougeron D et al (2016) Integrative analyses of colorectal cancer show immunoscore is a stronger predictor of patient survival than microsatellite instability. Immunity 44(3):698–711CrossRefGoogle Scholar
  9. 9.
    Kirilovsky A, Marliot F, Sissy CE, Haicheur N, Galon J, Pagès F (2016) Rational bases for the use of the immunoscore in routine clinical settings as a prognostic and predictive biomarker in cancer patients. Int Immunol 28:216–226CrossRefGoogle Scholar
  10. 10.
    Mlecnik B, Van den Eynde M, Bindea G, Church SE, Vasaturo A, Fredriksen T et al (2018) Comprehensive intrametastatic immune quantification and major impact of immunoscore on survival. J Natl Cancer Inst.  https://doi.org/10.1093/jnci/djx123 Google Scholar
  11. 11.
    Anitei MG, Zeitoun G, Mlecnik B, Marliot F, Haicheur N, Todosi AM et al (2014) Prognostic and predictive values of the immunoscore in patients with rectal cancer. Clin Cancer Res 20(7):1891–1899CrossRefGoogle Scholar
  12. 12.
    Rabjerg M (2017) Identification and validation of novel prognostic markers in renal cell carcinoma. Dan Med J 64(10):B5339Google Scholar
  13. 13.
    Fridman WH, Pagès F, Sautès-Fridman C, Galon J (2012) The immune contexture in human tumours: impact on clinical outcome. Nat Rev Cancer 12:298–306CrossRefGoogle Scholar
  14. 14.
    Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674CrossRefGoogle Scholar
  15. 15.
    Fridman WH, Zitvogel L, Sautès-Fridman C, Kroemer G (2017) The immune contexture in cancer prognosis and treatment. Nat Rev Clin Oncol 14(12):717–734CrossRefGoogle Scholar
  16. 16.
    Ingels A, Salas RES, Ravery V, Fromont-Hankard G, Validire P, Patard JJ et al (2014) T-helper 1 immunoreaction influences survival in muscle-invasive bladder cancer: proof of concept. Ecancer Med Sci 8:486Google Scholar
  17. 17.
    Sharma P, Shen Y, Wen S, Yamada S, Jungbluth AA, Gnjatic S et al (2007) CD8 tumor-infiltrating lymphocytes are predictive of survival in muscle-invasive urothelial carcinoma. Proc Natl Acad Sci USA 104:3967–3972CrossRefGoogle Scholar
  18. 18.
    Ascierto PA, Capone M, Urba WJ, Bifulco CB, Botti G, Lugli A et al (2013) The additional facet of immunoscore: immunoprofiling as a possible predictive tool for cancer treatment. Journal of Translational Medicine 11:54–57CrossRefGoogle Scholar
  19. 19.
    Yu A, Mansure JJ, Solanki S, Siemens DR, Koti M, Dias ABT et al (2018) Presence of lymphocytic infiltrate cytotoxic T lymphocyte CD3+ , CD8+ , and immunoscore as prognostic marker in patients after radical cystectomy. PLoS One 13(10):e0205746.  https://doi.org/10.1371/journal.pone.0205746.eCollection2018 CrossRefGoogle Scholar
  20. 20.
    Galon J, Pagès F, Marincola FM, Angell HK, Thurin M, Lugli A et al (2012) Cancer classification using the immunoscore: a worldwide task force. J Transl Med 10:205–213CrossRefGoogle Scholar
  21. 21.
    Sun C, Xu J, Song J, Liu CQ, Wang J, Weng C et al (2015) The predictive value of centre tumour CD8+ T cells in patients with hepatocellular carcinoma: comparison with immunoscore. Oncotarget 34:35602–35615Google Scholar
  22. 22.
    Mlecnik B, Tosolini M, Kirilovsky A, Berger A, Bindea G, Meatchi T et al (2011) Histopathologic-based prognostic factors of colorectal cancers are associated with the state of the local immune reaction. J Clin Oncol 29:610–618CrossRefGoogle Scholar
  23. 23.
    Faraj S, Munari E, Guner G, Taube J, Anders R, Hicks J et al (2015) Assessment of tumoral PD-L1 expression and intratumoral CD8+ T cells in urothelial carcinoma. Urology 85:703–708CrossRefGoogle Scholar
  24. 24.
    Horn T, Laus J, Seitz AK, Maurer T, Schmid SC, Wolf P et al (2016) The prognostic effect of tumour-infiltrating lymphocytic subpopulations in bladder cancer. World J Urol 34:181–187CrossRefGoogle Scholar
  25. 25.
    Baine MK, Turcu G, Zito CR, Adeniran AJ, Camp RL, Chen L et al (2015) Characterization of tumor infiltrating lymphocytes in paired primary and metastatic renal cell carcinoma specimens. Oncotarget 6:24990–25002CrossRefGoogle Scholar
  26. 26.
    Harter PN, Bernatz S, Scholz A, Zeiner PS, Zinke J, Kiyose M et al (2015) Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases. Oncotarget 6(38):40836–40849CrossRefGoogle Scholar
  27. 27.
    Nivolumab in Treating Patients With Localized Kidney Cancer Undergoing Nephrectomy (PROSPER). NCT03055013. https://clinicaltrials.gov/ct2/home. Accessed 24 May 2017
  28. 28.
    A Study of Atezolizumab as Adjuvant Therapy in Participants With Renal Cell Carcinoma (RCC) at High Risk of Developing Metastasis Following Nephrectomy (IMmotion010). NCT03024996 Available at:https://clinicaltrials.gov/ct2/home. Accessed 24 May 2017
  29. 29.
    Zahoor H, Pavicic PG Jr, Przybycin C, Ko J, Stephens L, Radivoyevitch T et al (2018) Evaluation of T cell infiltration in matched biopsy and nephrectomy samples in renal cell carcinoma. Medicine (Baltimore) 97(37):e12344CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of UrologyKarabük University Training and Research HospitalKarabükTurkey
  2. 2.Department of Medical OncologyHealth Science University Dr, Abdurrahman Yurtaslan Ankara Oncology Training and Research HospitalAnkaraTurkey
  3. 3.Department of PathologyHealth Science University Dr, Abdurrahman Yurtaslan Ankara Oncology Training and Research HospitalAnkaraTurkey
  4. 4.Department of UrologyHealth Science University Dr, Abdurrahman Yurtaslan Ankara Oncology Training and Research HospitalAnkaraTurkey

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