Células reguladoras en cáncer de piel melanoma y no melanoma
Palabras clave:
cáncer de piel, melanoma, células T reguladoras, carcinoma basocelular, carcinoma escamocelular
Resumen
Las células T reguladoras (Treg) CD4+CD25+FOXP3+ son cruciales para el
mantenimiento de la tolerancia y la prevención de la autoinmunidad. Su deficiencia se asocia con enfermedades autoinmunitarias y alergias, y su aumento se
relaciona con el cáncer. La manipulación de las Treg es un objetivo de los estudios de inmunología del cáncer, debido a los potenciales efectos antitumorales.
Las células Treg se producen en el timo y en la periferia. La radiación ultravioleta es capaz de suprimir la respuesta inmunitaria en la piel, entre otros mecanismos, por la inducción de las Treg, y esto se asocia al desarrollo de cáncer de
piel melanoma y no melanoma.
En este artículo se revisan los aspectos esenciales de las células Treg, su relación con la radiación ultravioleta y el cáncer, específicamente el cáncer de piel
melanoma y no melanoma.
Citas
1. Abbas AK, Lichtman AH, Pillai S. Inmunología celular y molecular. Sexta edición. Barcelona, España: Elsevier Inc.; 2008.
2. Jiang H, Chess L. Regulation of immune responses by T cells. N Engl J Med. 2006;354:1166-76.
3. M.G. Label, R.Kolliker-Frers,A.Woscoff, P.Troielli. Regulación de la respuesta inmune. Células T reguladoras-supresoras. Parte I. Dermatología Argentina. 2005; 11:132- 7
4. Beissert S, Schwarz A, Schwarz T. Regulatory T cells. J Invest Dermatol. 2006; 126:15-24.
5. Fehérvari Z, Sakaguchi S. CD4 + Tregs and immune control. J Clin Invest. 2004; 114:1209-17.
6. Lima HC. Role of regulatory T cells in the development of skin diseases. An Bras Dermatol. 2006; 81:269-81.
7. Melencio L, McKallip RJ, Guan H, Ramakrishnan R, Jain R, Nagarkatti PS, et al. Role of CD4(+)CD25(+) T regulatory cells in IL-2-induced vascular leak.. Int Immunol. 2006; 18:1461-71.
8. Wang HY, Wang RF. Regulatory T cells and cancer. Curr Opin Immunol. 2007; 19:217-23.
9. Luis J, Parias G, Giraldo VED, Velásquez-Lopera MM. Foxp3: Controlador maestro de la generación y función de las células reguladoras naturales. Inmunología 2010; 291-11.
10. Dudda JC, Perdue N, Bachtanian E, Campbell DJ. Foxp3+ regulatory T cells maintain immune homeostasis in the skin. J Exp Med. 2008; 205:1559-65.
11. Polansky JK, Kretschmer K, Freyer J, Floess S, Garbe A, Baron U, et al. DNA methylation controls Foxp3 gene expression. Eur J Immunol 2008; 38(6):1654-63.
12. Cavanagh LL, Halliday GM. Dendritic epidermal T cells in ultraviolet-irradiated skin enhances skin tumor growth by inhibiting CD4+ T-cell-mediated immunity. Cancer Res J. 1996; 56:2607-15
13. Fu B-Mang, He X-Shun, Yu S, Hu A-bin, Zhang J, Ma Y, et al. A tolerogenic semimature dendritic cells induce effector T-cell hyporesponsiveness by activation of antigen-specific CD4+CD25+ T regulatory cells that promotes skin allograft survival in mice. Cell Immunol 2009; 261:69-76.
14. Jang TJ. Prevalence of Foxp3 positive T regulatory cells is increased during progression of cutaneous squamous tumors. Yonsei Med J. 2008; 49:942-8.
15. D’Ambrosio D. Regulatory T cells: How do they find their space in the immunological arena?. Semin Cancer Biol. 2006; 16:91-7.
16. Clark RA. Skin-resident T cells: The ups and downs of onsite immunity. J Invest Dermatol. 2010; 130:362-70.
17. Beyer M, Schultze JL. Regulatory T cells in cancer. Blood. 2006; 108:804-11.
18. Wang R-F. CD8+ regulatory T cells, their suppressive mechanisms, and regulation in cancer. Human Immunol 2008; 69:811-4.
19. Birch KE, Reed JR, Akbar AN, Rustin MHA, Birch K. The immunomodulatory effects of regulatory T cells: Implications for immune regulation in the skin. Br J Dermatol. 2005; 152:409-17.
20. Prendergast GC, Metz R. IDO recruits Tregs in melanoma A side-by-side comparison of. Cell Cycle. 2009; 8:1818-22.
21. Ilkovitch D. Role of immune-regulatory cells in skin pathology. J Leukoc Biol. 2010; 89:1-9.
22. Gruijl FR. Ultraviolet radiation and tumor immunity. Methods (San Diego, Calif.). 2002; 28:122-9.
23. Beissert S, Loser K. Molecular and cellular mechanisms of photocarcinogenesis. Photochem Photobiol. 2008; 84:29-34.
24. Wang L, Toda M, Saito K, Hori T, Horii T, Shiku H, et al. Post-immune UV irradiation induces Tr1-like regulatory T cells that suppress humoral immune responses. Int Immunol. 2008; 20:57-70.
25. Rana S, Byrne SN, MacDonald LJ, Chan CY-Y, Halliday GM. Ultraviolet B suppresses immunity by inhibiting effector and memory T cells. [Internet]. Am J Pathol. 2008; 172:993-1004.
26. Noonan FP, Muller HK, Fears TR, Kusewitt DF, Johnson TM, De Fabo EC. Mice with genetically determined high susceptibility to ultraviolet (UV)-induced immunosuppression show enhanced UV carcinogenesis. J Invest Dermatol. 2003; 121:1175-81.
27. Maeda A, Beissert S, Schwarz T, Schwarz A. Phenotypic and functional characterization of ultraviolet radiation-induced regulatory T cells. J Immunol 2008; 180:3065-71.
28. Loser K, Apelt J, Voskort M, Mohaupt M, Balkow S, Schwarz T, et al. IL-10 controls ultraviolet-induced carcinogenesis in mice. J Immunol 2007; 179:365-71
29. Schwarz a, Beissert S, Grosse-Heitmeyer K, Gunzer M, Bluestone JA, Grabbe S, et al. Evidence for functional relevance of CTLA-4 in ultraviolet-radiation-induced tolerance. J Immunol 2000; 165:1824-31.
30. Schwarz A, Maeda A, Ständer S, van Steeg H, Schwarz T. IL-18 reduces ultraviolet radiation-induced DNA damage and thereby affects photoimmunosuppression. J Immunol 2006; 176:2896-901.
31. Meeran SM, Katiyar S, Elmets CA, Katiyar SK. Interleukin-12 deficiency is permissive for angiogenesis in UV radiationinduced skin tumors. Cancer Res. 2007; 67:3785-93.
32. Schwarz T. Regulatory T cells induced by ultraviolet radiation. Int Arch Allergy Immunol. 2005; 445:1-7.
33. Loser K, Beissert S. Regulation of cutaneous immunity by the environment: An important role for UV irradiation and vitamin D. Int Immunopharmacol. 2009; 9:587-9
34. Ghoreishi M, Bach P, Obst J, Komba M, Fleet JC, Dutz JP. Expansion of antigen-specific regulatory T cells with the topical vitamin D analog calcipotriol. J Immunol 2009; 182:6071-8.
35. Katiyar S. Interleukin-12 and photocarcinogenesis. Toxicol Appl Pharmacol. 2007; 224:220-7
36. Meeran SM, Mantena SK, Meleth S, Elmets CA, Katiyar SK. Interleukin-12-deficient mice are at greater risk of UV radiation-induced skin tumors and malignant transformation of papillomas to carcinomas. Mol Cancer Ther. 2006; 5:825-32.
37. Meeran SM, Mantena SK, Katiyar SK. Prevention of ultraviolet radiation-induced immunosuppression by (-)-epigallocatechin-3-gallate in mice is mediated through interleukin 12-dependent DNA repair. Clin Cancer Res. 2006; 12:2272-80.
38. Piersma SJ, Welters MJP, van der Burg SH. Tumor-specific regulatory T cells in cancer patients. Human Immunol. 2008; 69:241-9.
39. Antony PA, Restifo PN CD4+ CD25+ T regulatory cells, immunotherapy of cancer, and interleukin-2 . J Immunother. 2005; 28:120-8.
40. Moodycliffe AM, Nghiem D, Clydesdale G, Ullrich SE. Immune suppression and skin cancer development: Regulation by NKT cells. Nat Immunol. 2000; 1:521-5
41. Ha T-Y. The role of regulatory T cells in cancer. Immune Netw. 2009; 9:209-35.
42. Baecher-Allan C, Anderson DE. Regulatory cells and human cancer. Semin Cancer Biol. 2006; 16:98-105.
43. Wolf AM, Wolf D, Steurer M, Gastl G, Gunsilius E, Grubeckloebenstein B. Increase of regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res. 2003; 9:606-12.
44. Cao X. Regulatory T cells and immune tolerance to tumors. Immunol Res. 2010; 46:79-93.
45. Attia P, Maker AV, Haworth LR, Rogers-Freezer L, Rosenberg SA. Inability of a fusion protein of IL-2 and diphtheria toxin (Denileukin Diftitox, DAB389 IL-2, ONTAK) to eliminate regulatory T lymphocytes in patients with melanoma. J Immunother. 2005; 28:582-92.
46. Wolff K, Goldsmith LA, Katz SI. Fitzpatrick’s dermatology in general medicine. 7th edition. : Mc Graw Hill Medical; 2008. USA.
47. Baumgartner J, Wilson C, Palmer B, Richter D, Banerjee A, McCarter M. Melanoma induces immunosuppression by upregulating FOXP3(+) regulatory T cells. J Surg Res. 2007; 141:72-7.
48. Correll A, Tuettenberg A, Becker C, Jonuleit H. Increased regulatory T-cell frequencies in patients with advanced melanoma correlate with a generally impaired T-cell responsiveness and are restored after dendritic cell-based vaccination. Exp Dermatol. 2010; 19:213-21.
49. Mahnke K, Schönfeld K, Fondel S, Ring S, Karakhanova S, Wiedemeyer K, et al. Depletion of CD4+CD25+ human regulatory T cells in vivo: Kinetics of Treg depletion and alterations in immune functions in vivo and in vitro.. Int J Cancer. 2007; 120:2723-33.
50. Tuettenberg A, Becker C, Huter E, Knop J, Enk AH, Jonuleit H. Induction of strong and persistent MelanA/MART-1- specific immune responses by adjuvant dendritic cell-based vaccination of stage II melanoma patients. Int J Cancer. 2006; 118:2617-27.16
51. Maeda A, Schneider SW, Kojima M, Beissert S, Schwarz T, Schwarz A. Enhanced photocarcinogenesis in interleukin-12- deficient mice. Cancer Res. 2006; 66:2962-9.
52. Welsh MM, Applebaum KM, Spencer SK, Perry AE, Karagas MR, Nelson HH. CTLA4 variants, UV-induced tolerance, and risk of non-melanoma skin cancer. Cancer Res. 2009; 69:6158-63.
53. Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ transplantation. N Engl J Med. 2003; 348:1681-91
54. Dreno B. Skin cancers after transplantation. Nephrol Dial Transplant. 2003; 18:1052-8
55. Kaporis HG, Guttman-Yassky E, Lowes MA, Haider AS, Fuentes-Duculan J, Darabi K, et al. Human basal cell carcinoma is associated with Foxp3+ T cells in a Th2 dominant microenvironment. J Invest Dermatol. 2007; 127:2391-8.
2. Jiang H, Chess L. Regulation of immune responses by T cells. N Engl J Med. 2006;354:1166-76.
3. M.G. Label, R.Kolliker-Frers,A.Woscoff, P.Troielli. Regulación de la respuesta inmune. Células T reguladoras-supresoras. Parte I. Dermatología Argentina. 2005; 11:132- 7
4. Beissert S, Schwarz A, Schwarz T. Regulatory T cells. J Invest Dermatol. 2006; 126:15-24.
5. Fehérvari Z, Sakaguchi S. CD4 + Tregs and immune control. J Clin Invest. 2004; 114:1209-17.
6. Lima HC. Role of regulatory T cells in the development of skin diseases. An Bras Dermatol. 2006; 81:269-81.
7. Melencio L, McKallip RJ, Guan H, Ramakrishnan R, Jain R, Nagarkatti PS, et al. Role of CD4(+)CD25(+) T regulatory cells in IL-2-induced vascular leak.. Int Immunol. 2006; 18:1461-71.
8. Wang HY, Wang RF. Regulatory T cells and cancer. Curr Opin Immunol. 2007; 19:217-23.
9. Luis J, Parias G, Giraldo VED, Velásquez-Lopera MM. Foxp3: Controlador maestro de la generación y función de las células reguladoras naturales. Inmunología 2010; 291-11.
10. Dudda JC, Perdue N, Bachtanian E, Campbell DJ. Foxp3+ regulatory T cells maintain immune homeostasis in the skin. J Exp Med. 2008; 205:1559-65.
11. Polansky JK, Kretschmer K, Freyer J, Floess S, Garbe A, Baron U, et al. DNA methylation controls Foxp3 gene expression. Eur J Immunol 2008; 38(6):1654-63.
12. Cavanagh LL, Halliday GM. Dendritic epidermal T cells in ultraviolet-irradiated skin enhances skin tumor growth by inhibiting CD4+ T-cell-mediated immunity. Cancer Res J. 1996; 56:2607-15
13. Fu B-Mang, He X-Shun, Yu S, Hu A-bin, Zhang J, Ma Y, et al. A tolerogenic semimature dendritic cells induce effector T-cell hyporesponsiveness by activation of antigen-specific CD4+CD25+ T regulatory cells that promotes skin allograft survival in mice. Cell Immunol 2009; 261:69-76.
14. Jang TJ. Prevalence of Foxp3 positive T regulatory cells is increased during progression of cutaneous squamous tumors. Yonsei Med J. 2008; 49:942-8.
15. D’Ambrosio D. Regulatory T cells: How do they find their space in the immunological arena?. Semin Cancer Biol. 2006; 16:91-7.
16. Clark RA. Skin-resident T cells: The ups and downs of onsite immunity. J Invest Dermatol. 2010; 130:362-70.
17. Beyer M, Schultze JL. Regulatory T cells in cancer. Blood. 2006; 108:804-11.
18. Wang R-F. CD8+ regulatory T cells, their suppressive mechanisms, and regulation in cancer. Human Immunol 2008; 69:811-4.
19. Birch KE, Reed JR, Akbar AN, Rustin MHA, Birch K. The immunomodulatory effects of regulatory T cells: Implications for immune regulation in the skin. Br J Dermatol. 2005; 152:409-17.
20. Prendergast GC, Metz R. IDO recruits Tregs in melanoma A side-by-side comparison of. Cell Cycle. 2009; 8:1818-22.
21. Ilkovitch D. Role of immune-regulatory cells in skin pathology. J Leukoc Biol. 2010; 89:1-9.
22. Gruijl FR. Ultraviolet radiation and tumor immunity. Methods (San Diego, Calif.). 2002; 28:122-9.
23. Beissert S, Loser K. Molecular and cellular mechanisms of photocarcinogenesis. Photochem Photobiol. 2008; 84:29-34.
24. Wang L, Toda M, Saito K, Hori T, Horii T, Shiku H, et al. Post-immune UV irradiation induces Tr1-like regulatory T cells that suppress humoral immune responses. Int Immunol. 2008; 20:57-70.
25. Rana S, Byrne SN, MacDonald LJ, Chan CY-Y, Halliday GM. Ultraviolet B suppresses immunity by inhibiting effector and memory T cells. [Internet]. Am J Pathol. 2008; 172:993-1004.
26. Noonan FP, Muller HK, Fears TR, Kusewitt DF, Johnson TM, De Fabo EC. Mice with genetically determined high susceptibility to ultraviolet (UV)-induced immunosuppression show enhanced UV carcinogenesis. J Invest Dermatol. 2003; 121:1175-81.
27. Maeda A, Beissert S, Schwarz T, Schwarz A. Phenotypic and functional characterization of ultraviolet radiation-induced regulatory T cells. J Immunol 2008; 180:3065-71.
28. Loser K, Apelt J, Voskort M, Mohaupt M, Balkow S, Schwarz T, et al. IL-10 controls ultraviolet-induced carcinogenesis in mice. J Immunol 2007; 179:365-71
29. Schwarz a, Beissert S, Grosse-Heitmeyer K, Gunzer M, Bluestone JA, Grabbe S, et al. Evidence for functional relevance of CTLA-4 in ultraviolet-radiation-induced tolerance. J Immunol 2000; 165:1824-31.
30. Schwarz A, Maeda A, Ständer S, van Steeg H, Schwarz T. IL-18 reduces ultraviolet radiation-induced DNA damage and thereby affects photoimmunosuppression. J Immunol 2006; 176:2896-901.
31. Meeran SM, Katiyar S, Elmets CA, Katiyar SK. Interleukin-12 deficiency is permissive for angiogenesis in UV radiationinduced skin tumors. Cancer Res. 2007; 67:3785-93.
32. Schwarz T. Regulatory T cells induced by ultraviolet radiation. Int Arch Allergy Immunol. 2005; 445:1-7.
33. Loser K, Beissert S. Regulation of cutaneous immunity by the environment: An important role for UV irradiation and vitamin D. Int Immunopharmacol. 2009; 9:587-9
34. Ghoreishi M, Bach P, Obst J, Komba M, Fleet JC, Dutz JP. Expansion of antigen-specific regulatory T cells with the topical vitamin D analog calcipotriol. J Immunol 2009; 182:6071-8.
35. Katiyar S. Interleukin-12 and photocarcinogenesis. Toxicol Appl Pharmacol. 2007; 224:220-7
36. Meeran SM, Mantena SK, Meleth S, Elmets CA, Katiyar SK. Interleukin-12-deficient mice are at greater risk of UV radiation-induced skin tumors and malignant transformation of papillomas to carcinomas. Mol Cancer Ther. 2006; 5:825-32.
37. Meeran SM, Mantena SK, Katiyar SK. Prevention of ultraviolet radiation-induced immunosuppression by (-)-epigallocatechin-3-gallate in mice is mediated through interleukin 12-dependent DNA repair. Clin Cancer Res. 2006; 12:2272-80.
38. Piersma SJ, Welters MJP, van der Burg SH. Tumor-specific regulatory T cells in cancer patients. Human Immunol. 2008; 69:241-9.
39. Antony PA, Restifo PN CD4+ CD25+ T regulatory cells, immunotherapy of cancer, and interleukin-2 . J Immunother. 2005; 28:120-8.
40. Moodycliffe AM, Nghiem D, Clydesdale G, Ullrich SE. Immune suppression and skin cancer development: Regulation by NKT cells. Nat Immunol. 2000; 1:521-5
41. Ha T-Y. The role of regulatory T cells in cancer. Immune Netw. 2009; 9:209-35.
42. Baecher-Allan C, Anderson DE. Regulatory cells and human cancer. Semin Cancer Biol. 2006; 16:98-105.
43. Wolf AM, Wolf D, Steurer M, Gastl G, Gunsilius E, Grubeckloebenstein B. Increase of regulatory T cells in the peripheral blood of cancer patients. Clin Cancer Res. 2003; 9:606-12.
44. Cao X. Regulatory T cells and immune tolerance to tumors. Immunol Res. 2010; 46:79-93.
45. Attia P, Maker AV, Haworth LR, Rogers-Freezer L, Rosenberg SA. Inability of a fusion protein of IL-2 and diphtheria toxin (Denileukin Diftitox, DAB389 IL-2, ONTAK) to eliminate regulatory T lymphocytes in patients with melanoma. J Immunother. 2005; 28:582-92.
46. Wolff K, Goldsmith LA, Katz SI. Fitzpatrick’s dermatology in general medicine. 7th edition. : Mc Graw Hill Medical; 2008. USA.
47. Baumgartner J, Wilson C, Palmer B, Richter D, Banerjee A, McCarter M. Melanoma induces immunosuppression by upregulating FOXP3(+) regulatory T cells. J Surg Res. 2007; 141:72-7.
48. Correll A, Tuettenberg A, Becker C, Jonuleit H. Increased regulatory T-cell frequencies in patients with advanced melanoma correlate with a generally impaired T-cell responsiveness and are restored after dendritic cell-based vaccination. Exp Dermatol. 2010; 19:213-21.
49. Mahnke K, Schönfeld K, Fondel S, Ring S, Karakhanova S, Wiedemeyer K, et al. Depletion of CD4+CD25+ human regulatory T cells in vivo: Kinetics of Treg depletion and alterations in immune functions in vivo and in vitro.. Int J Cancer. 2007; 120:2723-33.
50. Tuettenberg A, Becker C, Huter E, Knop J, Enk AH, Jonuleit H. Induction of strong and persistent MelanA/MART-1- specific immune responses by adjuvant dendritic cell-based vaccination of stage II melanoma patients. Int J Cancer. 2006; 118:2617-27.16
51. Maeda A, Schneider SW, Kojima M, Beissert S, Schwarz T, Schwarz A. Enhanced photocarcinogenesis in interleukin-12- deficient mice. Cancer Res. 2006; 66:2962-9.
52. Welsh MM, Applebaum KM, Spencer SK, Perry AE, Karagas MR, Nelson HH. CTLA4 variants, UV-induced tolerance, and risk of non-melanoma skin cancer. Cancer Res. 2009; 69:6158-63.
53. Euvrard S, Kanitakis J, Claudy A. Skin cancers after organ transplantation. N Engl J Med. 2003; 348:1681-91
54. Dreno B. Skin cancers after transplantation. Nephrol Dial Transplant. 2003; 18:1052-8
55. Kaporis HG, Guttman-Yassky E, Lowes MA, Haider AS, Fuentes-Duculan J, Darabi K, et al. Human basal cell carcinoma is associated with Foxp3+ T cells in a Th2 dominant microenvironment. J Invest Dermatol. 2007; 127:2391-8.
Cómo citar
1.
Escobar C, Velásquez MM. Células reguladoras en cáncer de piel melanoma y no melanoma. rev. asoc. colomb. dermatol. cir. dematol. [Internet]. 4 de marzo de 2019 [citado 14 de abril de 2021];19(4):295-04. Disponible en: https://revista.asocolderma.org.co/index.php/asocolderma/article/view/351
Descargas
La descarga de datos todavía no está disponible.
