Summary
To investigate the relationship between keratoacanthoma (KA) and squamous cell carcinoma (SCC), cytokine mRNA in 12 KA and eight SCC were compared. Normal skin was also studied. Reverse transcription polymerase chain reaction (RT-PCR) was used to quantitate mRNA in each sample utilizing DNA standards. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was used as an internal control, and CD3δ as an indication of the T-cell infiltrate. KAs showed a significant increase in interleukin (IL)-10, and a decrease in granulocyte macrophage colony-stimulating factor (GM-CSF) mRNA compared to SCCs. CD3δ mRNA was also increased in the KAs. There was no difference between KAs and SCCs in expression of lymphotoxin-α, IL-2, interferon-γ (IFN-γ), IL-13, transforming growth factor-β (TGF-β), or the pro-inflammatory cytokines IL-8 or tumour necrosis factor-α (TNF-α). These results indicate that KAs spontaneously resolve in an immunosuppressive environment. KAs grow rapidly over a period of weeks and then involute. It is possible that a suppressed immune response enables unimpeded growth and that the KA cells rapidly undergo the finite number of cell divisions of which they are capable, and then die without reaching immortality.
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Bishop, G. A., Rokahr, K. L., Lowes, M., McGuinness, P. H., Napoli, J., DeCruz, D. J., Wong, W-Y & McCaughan, G. W. (1997). Quantitative reverse transcriptase-PCR amplification of cytokine mRNA in liver biopsy specimens using a non-competitive method. Immunol Cell Biol 75: 142–147.
Chomczynski, P. & Sacchi, N. (1987). Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Analyt Biochem 162: 156–159.
Dallman, M. J., Shiho, O., Page, T. H., Wood, K. J. & Morris, P. J. (1991). Peripheral tolerance to alloantigen results from altered regulation of the interleukin 2 pathway. J Exp Med 173: 79–87.
Dranoff, G., Jaffee, E., Lazenby, A., Golumbek, P., Levitsky, H., Brose, K., Jackson, V., Hamada, H., Pardoll, D. & Mulligan, R. C. (1993). Vaccination with irradiated tumor cells engineered to secrete murine granulocyte-macrophage colony-stimulating factor stimulates potent, specific, and long-lasting anti-tumor immunity. Proc Natl Acad Sci USA 90: 3539–3543.
Ehlers, S. & Smith, K. A. (1991). Differentiation of lymphokine gene expression: the in vitro acquisition of T cell memory. J Exp Med 173: 25–36.
Enk, A. H., Angeloni, V. L., Udey, M. C. & Katz, S. I. (1993). Inhibition of Langerhans cell antigen-presenting function by IL-10. J Immunol 151: 2390–2398.
Ghadially, R. & Ghadially, F. N. (1993). Keratoacanthoma. In Dermatology in General Medicine, Fitzpatrick TB, Eisen AZ, Wolff K, Freeberg IM and Austen KF (eds), pp. 848–855. McGraw-Hill: New York
Hunt, M. J., Halliday, G. M., Weedon, D., Cooke, B. E. & Barnetson, RStC (1994). Regression in basal cell carcinoma: an immunohistochemical analysis. Br J Dermatol 130: 1–8.
Kim, J., Modlin, R. L., Moy, R. L., Dubinett, S. M., McHugh, T., Nickoloff, B. J. & Uyemura, K. (1995). IL-10 production in cutaneous basal and squamous cell carcinomas. J Immunol 155: 2240–2247.
Kundu, N., Beaty, T. L., Jackson, M. J. & Fulton, A. M. (1996). Antimetastatic and antitumor activities of interleukin 10 in a murine model of breast cancer. J Natl Cancer Inst 88: 536–541.
Kurt, R. A., Park, J. A., Panelli, M. C., Schluter, S. F., Marchalonis, J. J., Carolus, B. & Akporiaye, E. T. (1995). T lymphocytes infiltrating sites of tumor rejection and progression display identical Vβ usage but different cytotoxic activities. J Immunol 154: 3969–3974.
Le Boit, P. E. (1995). Is keratoacanthoma a variant of squamous cell carcinoma. New insights into an old controversy … soon?. Am J Dermatopathol 17: 319–320.
Lowes, M. A., Bishop, G. A., Crotty, K., Barnetson, RStC & Halliday, G. M. (1997). T helper 1 cytokine mRNA is increased in spontaneously regressing primary melanomas. J Invest Dermatol 108: 914–919.
Mantovani, A. (1994). Tumor-associated macrophages in neoplastic progression: a paradigm for the in vivo function of chemokines. Lab Invest 71: 5–16.
Marks, R., Foley, P., Goodman, G., Hage, B. H. & Selwood, T. S. (1986). Spontaneous remission of solar keratoses: the case for conservative management. Br J Dermatol 115: 649–655.
Mosmann, T. R. (1994). Properties and functions of interleukin-10. Adv Immunol 56: 1–26.
Patel, A., Halliday, G. M., Cooke, B. E. & Barnetson, RStC (1994). Evidence that regression in keratoacanthoma is immunologically mediated: a comparison with squamous cell carcinoma. Br J Dermatol 131: 789–798.
Prehn, R. T. (1996). The paradoxical association of regression with a poor prognosis in melanoma contrasted with a good prognosis in keratoacanthoma. Cancer Res 56: 937–940.
Schwartz, R. A. (1994). Keratoacanthoma. J Am Acad Dermatol 30: 1–19.
Schwartz, R. A. & Stoll, H. L. (1993). Squamous cell carcinoma. In Dermatology in General Medicine, Fitzpatrick TB, Eisen AZ, Wolff K, Freeberg IM and Austen KF (eds), pp. 821–839. McGraw-Hill: New York
Si, Z., Hersey, P. & Coates, A. S. (1996). Clinical responses and lymphoid infiltrates in metastatic melanoma following treatment with intralesional GM-CSF. Mel Res 6: 247–255.
Tefany, F. J., Barnetson, RStC, Halliday, G. M., McCarthy, S. W. & McCarthy, W. H. (1991). Immunocytochemical analysis of the cellular infiltrate in primary regressing and non-regressing malignant melanoma. J Invest Dermatol 97: 197–202.
Yamamura, M., Modlin, R. L., Ohmen, J. D. & Moy, R. L. (1993). Local expression of anti-inflammatory cytokines in cancer. J Clin Invest 91: 1005–1010.
Yamamura, M., Uyemura, K., Deans, R. J., Weinberg, K., Rea, T. H., Bloom, B. R. & Modlin, R. L. (1991). Defining protective responses to pathogens: cytokine profiles in leprosy lesions. Science 254: 277–279.
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Lowes, M., Bishop, G., Cooke, B. et al. Keratoacanthomas have an immunosuppressive cytokine environment of increased IL-10 and decreased GM-CSF compared to squamous cell carcinomas. Br J Cancer 80, 1501–1505 (1999). https://doi.org/10.1038/sj.bjc.6690552
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.bjc.6690552