Proinflammatory cytokines in xeroderma pigmentosum (XP) and non-XP cancer patients-a pilot study

Kalthoum Abid , Jihene Bettaieb , Faouzi El Mezni , Hamouda Boussen

Exploration of Immunology ›› 2024, Vol. 4 ›› Issue (5) : 557 -567.

PDF (2021KB)
Exploration of Immunology ›› 2024, Vol. 4 ›› Issue (5) :557 -567. DOI: 10.37349/ei.2024.00159
Original Article
research-article
Proinflammatory cytokines in xeroderma pigmentosum (XP) and non-XP cancer patients-a pilot study
Author information +
History +
PDF (2021KB)

Abstract

Aim: Testing the feasibility of the determination to what extent the inability to repair DNA lesions in xeroderma pigmentosum (XP) patients, contributes to the alteration of immune responses, in the course of skin carcinogenesis.

Methods: Serum samples from 11 (five XP, six non-XP) bearing skin carcinomas and from three healthy donors, were available for the quantification of IL-2, IL-4, IL-10, IFN-γ and TNF-α cytokines concentrations. We used kits for ELISA test, by a non-competitive sandwich method. Statistical analysis of the results was performed, using non-parametric Mann-Whitney U test, with an accuracy of 5%.

Results: Our results showed that the majority of XP and non-XP cancer patients showed a significant increase in the secretion of TNF-α cytokine above healthy individuals (controls). TNF-α was also found to be significantly high in the serum of XP patients above that reported for the studied non-XP cancer patients. At the same time, TNF-α was not detected in the serum of non-XP and of healthy controls. This increase in the expression level of TNF-α was statistically significant between XP and non-XP patients, and between XP patients and controls. In contrast, there were no significant differences between XP patients and healthy controls, as well as between XP and non-XP patients, for the level of serum IL-2, IL-4 and IL-10 cytokines. On the other hand, we found no detectable levels of IFN-γ cytokine in the serum of all the studied subgroups.

Conclusions: In this study, we demonstrate a general tendency to secrete inflammatory cytokines, in the cancerous groups of patients (XP and non-XP), in comparison to healthy controls, while a significantly higher propensity to develop inflammation, in XP than in non-XP cancer patients.

Keywords

Xeroderma pigmentosum / skin carcinomas / DNA damage / cytokines / radiotherapy / chemotherapy / inflammation

Cite this article

Download citation ▾
Kalthoum Abid, Jihene Bettaieb, Faouzi El Mezni, Hamouda Boussen. Proinflammatory cytokines in xeroderma pigmentosum (XP) and non-XP cancer patients-a pilot study. Exploration of Immunology, 2024, 4 (5) : 557-567 DOI:10.37349/ei.2024.00159

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

de Gruijl FR, van der Leun JC. Estimate of the wavelength dependency of ultraviolet carcinogenesis in humans and its relevance to the risk assessment of a stratospheric ozone depletion. Health Phys. 1994; 67: 319-25.

[2]

Cleaver JE. Common pathways for ultraviolet skin carcinogenesis in the repair and replication defective groups of xeroderma pigmentosum. J Dermatol Sci. 2000; 23: 1-11.

[3]

Boonstra A, van Oudenaren A, Barendregt B, An L, Leenen PJ, Savelkoul HF. UVB irradiation modulates systemic immune responses by affecting cytokine production of antigen-presenting cells. Int Immunol. 2000; 12: 1531-8.

[4]

Weinstock MA. Death from skin cancer among the elderly: epidemiological patterns. Arch Dermatol. 1997; 133: 1207-9.

[5]

Gremmel T, Wild S, Schuller W, Kürten V, Dietz K, Krutmann J, et al. Six Genes Associated with the Clinical Phenotypes of Individuals with Deficient and Proficient DNA Repair. Translational oncogenomics. 2008; 3: 1-13.

[6]

Wood RD. Nucleotide excision repair in mammalian cells. J Biol Chem. 1997; 272: 23465-8.

[7]

Lehmann AR, McGibbon D, Stefanini M. Xeroderma pigmentosum. Orphanet J Rare Dis. 2011; 6: 70.

[8]

Gaspari AA, Fleisher TA, Kraemer KH. Impaired interferon production and natural killer cell activation in patients with the skin cancer-prone disorder, xeroderma pigmentosum. J Clin Invest. 1993; 92: 1135-42.

[9]

Miyauchi-Hashimoto H, Okamoto H, Tanaka K, Horio T. Ultraviolet radiation-induced suppression of natural killer cell activity is enhanced in xeroderma pigmentosum group A (XPA) model mice. J Invest Dermatol. 1999; 112: 965-70.

[10]

Jimbo T, Ichihashi M, Mishima Y, Fujiwara Y. Role of excision repair in UVB-induced depletion and recovery of human epidermal Langerhans cells. Arch Dermatol. 1992; 128: 61-7.

[11]

Castori M, Morrone A, Kanitakis J, Grammatico P. Genetic skin diseases predisposing to basal cell carcinoma. Eur J Dermatol. 2012; 22: 299-309.

[12]

van Engelen BG, Hiel JA, Gabreëls FJ, van den Heuvel LP, van Gent DC, Weemaes CM. Decreased immunoglobulin class switching in Nijmegen Breakage syndrome due to the DNA repair defect. Hum Immunol. 2001; 62: 1324-7.

[13]

Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002; 420: 860-7.

[14]

Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010; 140: 883-99.

[15]

Wang X, Lin Y. Tumor necrosis factor and cancer, buddies or foes? Acta Pharmacol Sin. 2008; 29: 1275-88.

[16]

Aggarwal BB. Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunol. 2003; 3: 745-56.

[17]

Ong ZY, Gibson RJ, Bowen JM, Stringer AM, Darby JM, Logan RM, et al. Pro-inflammatory cytokines play a key role in the development of radiotherapy-induced gastrointestinal mucositis. Radiat Oncol. 2010; 5: 22.

[18]

Shareef MM, Cui N, Burikhanov R, Gupta S, Satishkumar S, Shajahan S, et al. Role of tumor necrosis factor-alpha and TRAIL in high-dose radiation-induced bystander signaling in lung adenocarcinoma. Cancer Res. 2007; 67: 11811-20.

[19]

Hoffmann TK, Sonkoly E, Homey B, Scheckenbach K, Gwosdz C, Bas M, et al. Aberrant cytokine expression in serum of patients with adenoid cystic carcinoma and squamous cell carcinoma of the head and neck. Head Neck. 2007; 29: 472-8.

[20]

Kaskas NM, Moore-Medlin T, McClure GB, Ekshyyan O, Vanchiere JA, Nathan CA. Serum biomarkers in head and neck squamous cell cancer. JAMA Otolaryngol Head Neck Surg. 2014; 140: 5-11.

[21]

Teresa Pinto A, Laranjeiro Pinto M, Patrícia Cardoso A, Monteiro C, Teixeira Pinto M, Filipe Maia A, et al. Ionizing radiation modulates human macrophages towards a pro-inflammatory phenotype preserving their pro-invasive and pro-angiogenic capacities. Sci Rep. 2016; 6: 18765.

[22]

Multhoff G, Radons J. Radiation, inflammation, and immune responses in cancer. Front Oncol. 2012; 2: 58.

[23]

Sabitha M, Sanoj Rejinold N, Nair A, Lakshmanan VK, Nair SV, Jayakumar R. Development and evaluation of 5-fluorouracil loaded chitin nanogels for treatment of skin cancer. Carbohydr Polym. 2013; 91: 48-57.

[24]

Kirkup ME, Narayan S, Kennedy CT. Cutaneous recall reactions with systemic fluorouracil. Dermatology. 2003; 206: 175-6.

[25]

Wang L, Saito K, Toda M, Hori T, Torii M, Ma N, et al. UV irradiation after immunization induces type 1 regulatory T cells that suppress Th2-type immune responses via secretion of IL-10. Immunobiology. 2010; 215: 124-32.

[26]

Satoh-Takayama N. Heterogeneity and diversity of group 3 innate lymphoid cells: new cells on the block. Int Immunol. 2016; 28: 29-34.

[27]

Chi H, Barry SP, Roth RJ, Wu JJ, Jones EA, Bennett AM, et al. Dynamic regulation of pro- and anti-inflammatory cytokines by MAPK phosphatase 1 (MKP-1) in innate immune responses. Proc Natl Acad Sci U S A. 2006; 103: 2274-9.

[28]

Green VL, Michno A, Greenman J, Stafford ND. Effect of treatment on systemic cytokines in head and neck squamous cell carcinoma patients. Results Immunol. 2011; 2: 1-6.

[29]

Malek TR, Castro I. Interleukin-2 receptor signaling: at the interface between tolerance and immunity. Immunity. 2010; 33: 153-65.

[30]

Tang Q, Adams JY, Penaranda C, Melli K, Piaggio E, Sgouroudis E, et al. Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction. Immunity. 2008; 28: 687-97.

[31]

Terabe M, Park JM, Berzofsky JA. Role of IL-13 in regulation of anti-tumor immunity and tumor growth. Cancer Immunol Immunother. 2004; 53: 79-85.

[32]

Günaydın , Kesikli SA, Kansu E, Hoşal . Identification of the peripheral blood levels of interleukin-12, interleukin-10, and transforming growth factor-β in patients with laryngeal squamous cell carcinoma. Head neck. 2012; 34: 393-7.

[33]

Jebreel A, Mistry D, Loke D, Dunn G, Hough V, Oliver K, et al. Investigation of interleukin 10, 12 and 18 levels in patients with head and neck cancer. J Laryngol Otol. 2007; 121: 246-52.

[34]

Guermonprez P, Valladeau J, Zitvogel L, Théry C, Amigorena S. Antigen presentation and T cell stimulation by dendritic cells. Annu Rev Immunol. 2002; 20: 621-67.

[35]

Lee S, Cha J, Kim I, Yoon JC, Lee HJ, Park SW, et al. A high-throughput assay of NK cell activity in whole blood and its clinical application. Biochem Biophys Res Commun. 2014; 445: 584-90.

[36]

Verma C, Eremin JM, Robins A, Bennett AJ, Cowley GP, El-Sheemy MA, et al. Abnormal T regulatory cells (Tregs: FOXP3+, CTLA-4+), myeloid-derived suppressor cells (MDSCs: monocytic, granulocytic) and polarised T helper cell profiles (Th1, Th2, Th17) in women with large and locally advanced breast cancers undergoing neoadjuvant chemotherapy (NAC) and surgery: failure of abolition of abnormal treg profile with treatment and correlation of treg levels with pathological response to NAC . J Transl Med. 2013; 11: 16.

[37]

Ross C, Hansen MB, Schyberg T, Berg K. Autoantibodies to crude human leucocyte interferon (IFN), native human IFN, recombinant human IFN-alpha 2b and human IFN-gamma in healthy blood donors. Clin Exp Immunol. 1990; 82: 57-62.

[38]

Wongkulab P, Wipasa J, Chaiwarith R, Supparatpinyo K. Autoantibody to interferon-gamma associated with adult-onset immunodeficiency in non-HIV individuals in Northern Thailand. PLoS One. 2013; 8: e76371.

[39]

Bratke K, Goettsching H, Kuepper M, Geyer S, Luttmann W, Virchow JC. Interleukin-4 suppresses the cytotoxic potential of in vitro generated, adaptive regulatory CD4+ T cells by down-regulation of granzyme B . Immunology. 2009; 127: 338-44.

[40]

Ferrajoli A, Keating MJ, Manshouri T, Giles FJ, Dey A, Estrov Z, et al. The clinical significance of tumor necrosis factor-alpha plasma level in patients having chronic lymphocytic leukemia. Blood. 2002; 100: 1215-9.

[41]

Berberoglu U, Yildirim E, Celen O. Serum levels of tumor necrosis factor alpha correlate with response to neoadjuvant chemotherapy in locally advanced breast cancer. Int J Biol Markers. 2004; 19: 130-4.

[42]

Takagi K, Takagi M, Kanangat S, Warrington KJ, Shigemitsu H, Postlethwaite AE. Modulation of TNF-alpha gene expression by IFN-gamma and pamidronate in murine macrophages: regulation by STAT1-dependent pathways. J Immunol. 2005; 174: 1801-10.

[43]

Burnette B, Weichselbaum RR. Radiation as an immune modulator. Semin Radiat Oncol. 2013; 23: 273-80.

[44]

Cardin R, Piciocchi M, Bortolami M, Kotsafti A, Barzon L, Lavezzo E, et al. Oxidative damage in the progression of chronic liver disease to hepatocellular carcinoma: an intricate pathway. World J Gastroenterol. 2014; 20: 3078-86.

[45]

Poljšak B, Dahmane R. Free radicals and extrinsic skin aging. Dermatol Res Pract. 2012; 2012: 135206.

[46]

Geng Y, Chandrasekaran S, Hsu J, Gidwani M, Hughes AD, King MR. Phenotypic switch in blood: effects of pro-inflammatory cytokines on breast cancer cell aggregation and adhesion. PLoS One. 2013; 8: e54959.

[47]

Wang X, Montoyo-Pujol YG, Bermudez S, Corpas G, Martin A, Almazan F, et al. Serum Cytokine Profiles of Melanoma Patients and Their Association with Tumor Progression and Metastasis. J Oncol. 2021; 2021: 6610769.

[48]

Murdaca G, Negrini S, Magnani O, Penza E, Pellecchio M, Puppo F. Impact of pharmacogenomics upon the therapeutic response to etanercept in psoriasis and psoriatic arthritis. Expert Opin Drug Saf. 2017; 16: 1173-9.

PDF (2021KB)

0

Accesses

0

Citation

Detail

Sections
Recommended

/