Volume 25, Issue 2 (3-2021)                   ibj 2021, 25(2): 88-92 | Back to browse issues page

PMID: 33461943

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Background: TNF-α and IL-6 are both pleiotropic cytokines playing major roles in cancer-associated cytokine networks. They have previously been investigated for their function in skin malignancies, mostly melanomas, and studies on non-melanoma skin cancer (NMSC) patients are relatively rara. In this study, we aimed to investigate the associations of serum levels of IL-6 and TNF-α with NMSCs and its clinicopathological features. Methods: This cases-control study was carried out to assess the serum levels of TNF-α and IL-6 in 70 NMSC patients, in comparison with 30 healthy individuals, by means of flow cytometric bead-based immuneoassay. Results: Serum levels of both TNF-α and IL-6 were significantly higher in NMSC patients (6.470 vs. 4.355 pg/ml; p = 0.0468, respectively), compared to healthy individuals (3.205 vs. 0.000 pg/ml; p = 0.0126, respectively). In the subgroup analysis, squamous cell carcinomas patients had higher serum levels of IL-6 compared to healthy individuals (3.445 vs. 0.000 pg/ml; p = 0.0432). No other significant differences were observed in the serum levels of these two cytokines among different clinicopathological subgroups of the patients. Conclusion: The increased levels of TNF-α and IL-6 in NMSC patients can be introduced as an epiphenomenon of a complex cancer-induced cytokine cascade.
Type of Study: Full Length | Subject: Cancer Biology

1. Esteva A, Kuprel B, Novoa RA, Ko J, Swetter SM, Blau HM, Thrun S. Dermatologist-level classification of skin cancer with deep neural networks. Nature 2017; 542(7639): 115-118. [DOI:10.1038/nature21056]
2. Rangwala S, Tsai KY. Roles of the immune system in skin cancer. Br j dermatol 2011; 165(5): 953-965. [DOI:10.1111/j.1365-2133.2011.10507.x]
3. Grivennikov SI, Greten FR, Karin M. Immunity inflammation and cancer. Cell 2010; 140(6): 883-899. [DOI:10.1016/j.cell.2010.01.025]
4. Lin WW, Karin M. A cytokine-mediated link between innate immunity, inflammation, and cancer. The journal of clinical investigation 2007; 117(5): 1175-1183. [DOI:10.1172/JCI31537]
5. Lewis AM, Varghese S, Xu H, Alexander HR. Interleukin-1 and cancer progression: the emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment. Journal of translational medicine 2006; 4: 48. [DOI:10.1186/1479-5876-4-48]
6. Balkwill F. TNF-alpha in promotion and progression of cancer. Cancer metastasis reviews 2006; 25(3): 409-416. [DOI:10.1007/s10555-006-9005-3]
7. Mauer J, Denson JL, Brüning JC. Versatile functions for IL-6 in metabolism and cancer. Trends in immunology 2015; 36(2): 92-101. [DOI:10.1016/j.it.2014.12.008]
8. Lippitz BE, Harris RA. Cytokine patterns in cancer patients: A review of the correlation between interleukin 6 and prognosis. Oncoimmunology 2016; 5(5): e1093722. [DOI:10.1080/2162402X.2015.1093722]
9. Lederle W, Depner S, Schnur S, Obermueller E, Catone N, Just A, Fusenig NE, Mueller MM. IL-6 promotes malignant growth of skin SCCs by regulating a network of autocrine and paracrine cytokines. International journal of cancer 2011; 128(12): 2803-2814. [DOI:10.1002/ijc.25621]
10. Donia M, Kjeldsen JW, Svane IM. The controversial role of TNF in melanoma. Oncoimmunology 2016; 5(4): e1107699. [DOI:10.1080/2162402X.2015.1107699]
11. Balkwill F. Tumour necrosis factor and cancer. Nature reviews cancer 2009; 9(5): 361-371. [DOI:10.1038/nrc2628]
12. Wang X, Lin Y. Tumor necrosis factor and cancer buddies or foes? Acta pharmacologica Sinica 2008; 29(11): 1275-1288. [DOI:10.1111/j.1745-7254.2008.00889.x]
13. Kalliolias GD, Ivashkiv LB. TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nature reviews rheumatology 2016; 12(1): 49-62. [DOI:10.1038/nrrheum.2015.169]
14. Sasi SP, Yan X, Enderling H, Park D, Gilbert HY, Curry C, Coleman C, Hlatky L, Qin G, Kishore R, Goukassian DA. Breaking the 'harmony' of TNF-α signaling for cancer treatment. Oncogene 2012; 31(37): 4117-4127. [DOI:10.1038/onc.2011.567]
15. Bridge JA, Lee JC, Daud A, Wells JW, Bluestone JA. Cytokines chemokines, and other biomarkers of response for checkpoint inhibitor therapy in skin cancer. Frontiers in medicine (Lausanne) 2018; 5: 351. [DOI:10.3389/fmed.2018.00351]
16. World Medical Association. World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 2013; 310(20): 2191-2194. [DOI:10.1001/jama.2013.281053]
17. Wajant H. The role of TNF in cancer. Results and problems in cell differentiation 2009; 49: 1-15. [DOI:10.1007/400_2008_26]
18. Lippitz BE. Cytokine patterns in patients with cancer: a systematic review. The lancet oncology 2013; 14(6): e218-e28. [DOI:10.1016/S1470-2045(12)70582-X]
19. Holbrook J, Lara-Reyna S, Jarosz-Griffiths H, McDermott M. Tumour necrosis factor signalling in health and disease. F1000 research 2019; 8: F1000 Faculty Rev-111 [DOI:10.12688/f1000research.17023.1]
20. Josephs SF, Ichim TE, Prince SM, Kesari S, Marincola FM, Escobedo AR, Jafri A. Unleashing endogenous TNF-alpha as a cancer immunotherapeutic. Journal of translational medicine 2018; 16(1): 242. [DOI:10.1186/s12967-018-1611-7]
21. Jain A, Singh JA. Harms of TNF inhibitors in rheumatic diseases: a focused review of the literature. Immunotherapy 2013; 5(3): 265-299. [DOI:10.2217/imt.13.10]
22. Chen Y, Friedman M, Liu G, Deodhar A, Chu CQ. Do tumor necrosis factor inhibitors increase cancer risk in patients with chronic immune-mediated inflammatory disorders? Cytokine 2018; 101: 78-88. [DOI:10.1016/j.cyto.2016.09.013]
23. Ham B, Fernandez MC, D'Costa Z, Brodt P. The diverse roles of the TNF axis in cancer progression and metastasis. Trends in cancer research 2016; 11(1): 1-27.
24. Sheng Y, Li F, Qin Z. TNF Receptor 2 makes tumor necrosis factor a friend of tumors. Frontiers in immunology 2018; 9: 1170. [DOI:10.3389/fimmu.2018.01170]
25. Johnson DE, O'Keefe RA, Grandis JR. Targeting the IL-6/JAK/STAT3 signalling axis in cancer. Nature reviews clinical oncology 2018; 15(4): 234-248. [DOI:10.1038/nrclinonc.2018.8]
26. Depner S, Lederle W, Gutschalk C, Linde N, Zajonz A, Mueller MM. Cell type specific interleukin-6 induced responses in tumor keratinocytes and stromal fibroblasts are essential for invasive growth. International journal of cancer 2014; 135(3): 551-562. [DOI:10.1002/ijc.27951]