Soluble interleukin-2 receptor α and interleukin-2 serum levels in patients with basal cell carcinoma

Introduction Basal cell carcinoma (BCC) is an immunogenic neoplasm and the imbalance in Th1/Th2 cytokines expression seems to play the major role in pathogenesis and clinical behaviour of the tumour. Aim To investigate the association of soluble interleukin 2α receptor (sIL-2Rα) and interleukin-2 (IL-2) serum concentrations with BCC. Material and methods The study involved 110 individuals with BCC and 60 healthy age- and sex-matched volunteers. Serum levels of sIL-2Rα and IL-2 were measured using ELISA test. Results We found significantly (p = 0.027) increased sIL-2Rα serum levels in BCC patients, in comparison to healthy controls. Statistically (p = 0.04) higher sIL-2Rα levels were observed in patients with more advanced tumours. Serum levels of sIL-2Rα showed a significant linear (r = 0.24, p = 0.018) correlation with tumour size. The average IL-2 serum levels in BCC patients were statistically (p = 0.039) decreased compared to controls. Significantly (p = 0.0454) lower median IL-2 levels were observed in patients with more advanced tumours. A negative correlation between sIL-2Rα and IL-2 serum concentrations was revealed (r = –0.22; p = 0.027). Conclusions Our results testify to the importance of the IL-2/sIL-2Rα signalling pathway in pathogenesis of BCC, suggesting that IL-2 and sIL-2Rα might be considered as potential markers of disease and targets for immunotherapy in BCC patients.

[1]  O. Boyman,et al.  Use of enhanced interleukin-2 formulations for improved immunotherapy against cancer. , 2014, Current opinion in chemical biology.

[2]  Y. Fukabori,et al.  Clinical Significance of Serum Soluble T Cell Regulatory Molecules in Clear Cell Renal Cell Carcinoma , 2014, BioMed research international.

[3]  B. Lippitz,et al.  Cytokine patterns in patients with cancer: a systematic review. , 2013, The Lancet. Oncology.

[4]  Sheri L. Johnson,et al.  Tumor Site Immune Markers Associated with Risk for Subsequent Basal Cell Carcinomas , 2011, PLoS ONE.

[5]  Yesheng Wei,et al.  Association of the interleukin-2 polymorphisms with interleukin-2 serum levels and risk of nasopharyngeal carcinoma. , 2010, DNA and cell biology.

[6]  Bai-Cheng He,et al.  Exosomes derived from IL-12-anchored renal cancer cells increase induction of specific antitumor response in vitro: a novel vaccine for renal cell carcinoma. , 2009, International journal of oncology.

[7]  Hsu-Chueh Ho,et al.  Clinical significance of measuring levels of tumor necrosis factor-alpha and soluble interleukin-2 receptor in nasopharyngeal carcinoma , 2009, Acta oto-laryngologica.

[8]  L. Medenica,et al.  Cytokine concentrations in basal cell carcinomas of different histological types and localization. , 2008, Acta dermatovenerologica Alpina, Pannonica, et Adriatica.

[9]  T. Nomura,et al.  Regulatory T Cells and Immune Tolerance , 2008, Cell.

[10]  E. Tartour,et al.  Soluble interleukin‐2 receptor and metalloproteinase‐9 expression in head and neck cancer: prognostic value and analysis of their relationships , 2007, Clinical and experimental immunology.

[11]  T. Waldmann.  Anti-Tac (daclizumab, Zenapax) in the Treatment of Leukemia, Autoimmune Diseases, and in the Prevention of Allograft Rejection: A 25-Year Personal Odyssey , 2007, Journal of Clinical Immunology.

[12]  A. Balcerska,et al.  Serum level of soluble interleukin-2 receptor α correlates with the clinical course and activity of Wilms’ tumour and soft tissue sarcomas in children , 2007, Biomarkers.

[13]  T. Waldmann,et al.  Effective treatment of a murine model of adult T-cell leukemia using 211At-7G7/B6 and its combination with unmodified anti-Tac (daclizumab) directed toward CD25. , 2006, Blood.

[14]  Prahbjot Kaur,et al.  Basal Cell Carcinoma Progression Correlates With Host Immune Response and Stromal Alterations: A Histologic Analysis , 2006, The American Journal of dermatopathology.

[15]  T. Gambichler,et al.  Cytokine mRNA expression in basal cell carcinoma , 2006, Archives of Dermatological Research.

[16]  G. Botti,et al.  Soluble interleukin-2 receptor in stage I-III melanoma. , 2006, Cytokine.

[17]  R. Dummer,et al.  Mechanisms underlying imiquimod-induced regression of basal cell carcinoma in vivo. , 2003, Archives of dermatology.

[18]  S. Murakami,et al.  Serum soluble interleukin-2 receptor (IL-2R) and immunohistochemical staining of IL-2R/Tac antigen in colorectal cancer , 2002, International Journal of Clinical Oncology.

[19]  T. Waldmann.  The IL-2/IL-15 Receptor Systems: Targets for Immunotherapy , 2002, Journal of Clinical Immunology.

[20]  E. Tartour,et al.  Serum soluble interleukin–2 receptor concentrations as an independent prognostic marker in head and neck cancer , 2001, The Lancet.

[21]  R. Moy,et al.  Effect of perilesional injections of PEG-interleukin-2 on basal cell carcinoma. , 2000, Dermatologic surgery : official publication for American Society for Dermatologic Surgery [et al.].

[22]  G. Halliday,et al.  Cytokine profiles in spontaneously regressing basal cell carcinomas , 2000, The British journal of dermatology.

[23]  T. Waldmann,et al.  IL-2R alpha on one cell can present IL-2 to IL-2R beta/gamma(c) on another cell to augment IL-2 signaling. , 1998, Journal of immunology.

[24]  M. Wasik,et al.  Use of serum soluble interleukin-2 receptor levels to monitor the progression of cutaneous T-cell lymphoma. , 1998, Journal of the American Academy of Dermatology.

[25]  G. Halliday,et al.  Spontaneous regression of human melanoma/nonmelanoma skin cancer: Association with infiltrating CD4+ T cells , 1995, World Journal of Surgery.

[26]  D. Nelson,et al.  Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro. , 1985, Journal of immunology.

[27]  A. Balcerska,et al.  Serum soluble interleukin 2 receptor alpha in human cancer of adults and children: a review. , 2008, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[28]  T. Yoshikawa,et al.  Inhibition of peritoneal metastasis in an animal gastric cancer model by interferon-gamma and interleukin-2. , 2003, Anticancer Research.

[29]  K. Chow,et al.  Clinical significance of serum soluble interleukin 2 receptor-alpha in esophageal squamous cell carcinoma. , 2000, Clinical cancer research : an official journal of the American Association for Cancer Research.

[30]  S. von Kleist,et al.  Cytokine levels in whole blood cell cultures as parameters of the cellular immunologic activity in patients with malignant melanoma and basal cell carcinoma , 1993, Cancer.