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Cancer Immunology, Immunotherapy

Published in:

01-08-2010 | Original Article

Serum IgG against Candida predict survival in patients with metastatic renal cell carcinoma

Authors: Reinhold Ramoner, Andrea Rahm, Claudia E. Falkensammer, Nicolai Leonhartsberger, Martin Thurnher

Published in: Cancer Immunology, Immunotherapy | Issue 8/2010

Abstract

Background and aim

In contrast to hematologic malignancies, little is known about the role of fungi in the development and progression of solid tumors. This prompted us to analyze and correlate serum levels of different fungal IgG with survival of patients with metastatic renal cell carcinoma.

Patients and methods

Serum IgG to Candida sp., Saccharomyces cerevisiae and Aspergillus fumigatus were measured in a cross-sectional study in 64 patients with advanced disease. Univariate and multivariate analyses were chosen to study serum IgG as prognostic indicators.

Results

Median follow-up was 29.0 months (range 0.3–122). Median overall survival of patients, which tested negative for Candida IgG, was significantly increased (median not reached, >29 months) compared with Candida IgG positive patients (17.8 months, P = 0.002). Median survival of Saccharomyces IgG negative patients was 33.1 months as opposed to 19.4 months in Saccharomyces IgG positive patients, although this difference was not significant (P = 0.281). No difference in overall survival was found between Aspergillus IgG positive patients (28.0 months) and Aspergillus IgG negative patients (29.1 months) (P = 0.181). Cox backward-stepwise regression confirmed Candida IgG as the strongest predictor of survival in metastatic renal cell carcinoma patients (risk ratio 3.27, P = 0.001, [95% CI 1.86–5.73]).

Conclusion

Our findings suggest that IgG antibodies directed against yeast fungi and particularly against Candida but not against mold fungi have prognostic relevance.

Motzer RJ, Bander NH, Nanus DM (1996) Renal-cell carcinoma. N Engl J Med 335:865–875CrossRefPubMed

Cohen HT, McGovern FJ (2005) Renal-cell carcinoma. N Engl J Med 353:2477–2490CrossRefPubMed

Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J (1999) Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol 17:2530–2540PubMed

Mejean A, Oudard S, Thiounn N (2003) Prognostic factors of renal cell carcinoma. J Urol 169:821–827CrossRefPubMed

Motzer RJ, Bacik J, Schwartz LH, Reuter V, Russo P, Marion S et al (2004) Prognostic factors for survival in previously treated patients with metastatic renal cell carcinoma. J Clin Oncol 22:454–463CrossRefPubMed

Negrier S, Perol D, Menetrier-Caux C, Escudier B, Pallardy M, Ravaud A et al (2004) Interleukin-6, interleukin-10, and vascular endothelial growth factor in metastatic renal cell carcinoma: prognostic value of interleukin-6—from the Groupe Francais d’Immunotherapie. J Clin Oncol 22:2371–2378CrossRefPubMed

Gripp S, Moeller S, Bolke E, Schmitt G, Matuschek C, Asgari S et al (2007) Survival prediction in terminally ill cancer patients by clinical estimates, laboratory tests, and self-rated anxiety and depression. J Clin Oncol 25:3313–3320CrossRefPubMed

Zisman A, Pantuck AJ, Dorey F, Said JW, Shvarts O, Quintana D et al (2001) Improved prognostication of renal cell carcinoma using an integrated staging system. J Clin Oncol 19:1649–1657PubMed

Heng DY, Xie W, Regan MM, Warren MA, Golshayan AR, Sahi C et al (2009) Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study. J Clin Oncol 27:5794–5799CrossRefPubMed

10.

Viscoli C, Girmenia C, Marinus A, Collette L, Martino P, Vandercam B et al (1999) Candidemia in cancer patients: a prospective, multicenter surveillance study by the Invasive Fungal Infection Group (IFIG) of the European Organization for Research and Treatment of Cancer (EORTC). Clin Infect Dis 28:1071–1079CrossRefPubMed

11.

Kleinrath T, Gassner C, Lackner P, Thurnher M, Ramoner R (2007) Interleukin-4 promoter polymorphisms: a genetic prognostic factor for survival in metastatic renal cell carcinoma. J Clin Oncol 25:845–851CrossRefPubMed

12.

Babula O, Lazdane G, Kroica J, Linhares IM, Ledger WJ, Witkin SS (2005) Frequency of interleukin-4 (IL-4) -589 gene polymorphism and vaginal concentrations of IL-4, nitric oxide, and mannose-binding lectin in women with recurrent vulvovaginal candidiasis. Clin Infect Dis 40:1258–1262CrossRefPubMed

13.

Ramoner R, Rahm A, Gander H, Stollenwerk B, Falkensammer C, Leonhartsberger N et al (2008) Serum antibodies against Saccharomyces cerevisiae: a new prognostic indicator in metastatic renal-cell carcinoma. Cancer Immunol Immunother 57:1207–1214CrossRefPubMed

14.

Holtl L, Ramoner R, Zelle-Rieser C, Gander H, Putz T, Papesh C et al (2005) Allogeneic dendritic cell vaccination against metastatic renal cell carcinoma with or without cyclophosphamide. Cancer Immunol Immunother 54:663–670CrossRefPubMed

15.

Holtl L, Zelle-Rieser C, Gander H, Papesh C, Ramoner R, Bartsch G et al (2002) Immunotherapy of metastatic renal cell carcinoma with tumor lysate-pulsed autologous dendritic cells. Clin Cancer Res 8:3369–3376PubMed

16.

Lackner A, Stammberger H, Buzina W, Freudenschuss K, Panzitt T, Schosteritsch S et al (2005) Fungi: a normal content of human nasal mucus. Am J Rhinol 19:125–129PubMed

17.

Rindum JL, Stenderup A, Holmstrup P (1994) Identification of Candida albicans types related to healthy and pathological oral mucosa. J Oral Pathol Med 23:406–412CrossRefPubMed

18.

Hostetter MK (1996) An integrin-like protein in Candida albicans: implications for pathogenesis. Trends Microbiol 4:242–246CrossRefPubMed

19.

Acosta-Rodriguez EV, Rivino L, Geginat J, Jarrossay D, Gattorno M, Lanzavecchia A et al (2007) Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol 8:639–646CrossRefPubMed

20.

LeibundGut-Landmann S, Gross O, Robinson MJ, Osorio F, Slack EC, Tsoni SV et al (2007) Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17. Nat Immunol 8:630–638CrossRefPubMed

21.

Huang W, Na L, Fidel PL, Schwarzenberger P (2004) Requirement of interleukin-17A for systemic anti-Candida albicans host defense in mice. J Infect Dis 190:624–631CrossRefPubMed

22.

Iwakura Y, Nakae S, Saijo S, Ishigame H (2008) The roles of IL-17A in inflammatory immune responses and host defense against pathogens. Immunol Rev 226:57–79CrossRefPubMed

23.

Lopez Hanninen E, Kirchner H, Atzpodien J (1996) Interleukin-2 based home therapy of metastatic renal cell carcinoma: risks and benefits in 215 consecutive single institution patients. J Urol 155:19–25CrossRefPubMed

24.

Hoffmann R, Franzke A, Buer J, Sel S, Oevermann K, Duensing A et al (1999) Prognostic impact of in vivo soluble cell adhesion molecules in metastatic renal cell carcinoma. Br J Cancer 79:1742–1745CrossRefPubMed

25.

Negrier S, Escudier B, Gomez F, Douillard JY, Ravaud A, Chevreau C et al (2002) Prognostic factors of survival and rapid progression in 782 patients with metastatic renal carcinomas treated by cytokines: a report from the Groupe Francais d’Immunotherapie. Ann Oncol 13:1460–1468CrossRefPubMed

26.

Atzpodien J, Royston P, Wandert T, Reitz M (2003) Metastatic renal carcinoma comprehensive prognostic system. Br J Cancer 88:348–353CrossRefPubMed

27.

Donskov F, von der Maase H (2006) Impact of immune parameters on long-term survival in metastatic renal cell carcinoma. J Clin Oncol 24:1997–2005CrossRefPubMed

28.

Langowski JL, Zhang X, Wu L, Mattson JD, Chen T, Smith K et al (2006) IL-23 promotes tumour incidence and growth. Nature 442:461–465CrossRefPubMed

29.

Langowski JL, Kastelein RA, Oft M (2007) Swords into plowshares: IL-23 repurposes tumor immune surveillance. Trends Immunol 28:207–212CrossRefPubMed

30.

Gilmore BJ, Retsinas EM, Lorenz JS, Hostetter MK (1988) An iC3b receptor on Candida albicans: structure, function, and correlates for pathogenicity. J Infect Dis 157:38–46PubMed

31.

Waterman SR (1999) Web alert Host–microbe interactions: fungi/viruses/parasites. Curr Opin Microbiol 2:341–342CrossRefPubMed

32.

Gustafson KS, Vercellotti GM, Bendel CM, Hostetter MK (1991) Molecular mimicry in Candida albicans. Role of an integrin analogue in adhesion of the yeast to human endothelium. J Clin Invest 87:1896–1902CrossRefPubMed

33.

Motzer RJ, Bacik J, Murphy BA, Russo P, Mazumdar M (2002) Interferon-alfa as a comparative treatment for clinical trials of new therapies against advanced renal cell carcinoma. J Clin Oncol 20:289–296CrossRefPubMed

34.

Mekhail TM, Abou-Jawde RM, Boumerhi G, Malhi S, Wood L, Elson P et al (2005) Validation and extension of the Memorial Sloan–Kettering prognostic factors model for survival in patients with previously untreated metastatic renal cell carcinoma. J Clin Oncol 23:832–841CrossRefPubMed

Title: Serum IgG against Candida predict survival in patients with metastatic renal cell carcinoma
Authors: Reinhold Ramoner
Andrea Rahm
Claudia E. Falkensammer
Nicolai Leonhartsberger
Martin Thurnher
Publication date: 01-08-2010
Publisher: Springer-Verlag
Published in: Cancer Immunology, Immunotherapy / Issue 8/2010
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-010-0827-z

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Background and aim

Patients and methods

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Conclusion

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