TUMOR-INFILTRATING CD1A+ LANGERHANS CELLS IN PRIMARY CUTANEOUS MELANOMA – AN IMMUNOHISTOCHEMICAL STUDY
Abstract
We highlight in this paper the main immunological roles of dendritis cells (DCs) in cancer, specifically in melanoma. The presence of dendritic cells in the tumor microenvironment triggers an effective antitumor immunity by recruiting of infiltrating tumor lymphocytes. Moreover, DCs also have the role of regulating and maintaining immune responses. DCs are present in both normal skin and melanocytic skin lesions. At the normal skin level, DCs are predominantly in the epidermis with few located in the dermis and few others that migrate in the circulation. However, in melanocytic lesions such as benign and dysplastic nevi, an increase in the density of DCs in the dermis is observed, with coexpression of CD1 and S100 markers. The aim of the study is to investigate CD1a expression in primary cutaneous melanoma. Regarding this, we conducted a retrospective transverse study of 37 cases of primary superficial spreading melanoma. We analyzed the clinical and histopatogica aspects of our group of study and we performed some correlations between CD1a expression and clinical and histopathological parameters. These correlations were tested using nonparametric tests such as Pearson and Spearman tests. The threshold for p values was considered statistical significant for 0.05. After performing Pearson test we found that CD1a positivity correlates statistically with Breslow index (p=0.017, r=0.434), Clark level (p=0.012, r=0.454), mitotic rate (p=0,036, r=0,390) and the ulceration of the tumor (p=0.044, r=0.370), with a moderate statistical power. Spearman test also showed positive correlation between CD1a expression and Breslow thickness (p=0,001, Sperman’s rho=0,593), Clark level (p=0,10, Sperman’s rho=0,465) and tumor ulceration (p=0,033, Sperman’s rho=0,391).
References
[2] M. R. Hussein, “Dendritic cells and melanoma tumorigenesis an insight,” Cancer Biol. Ther., vol. 4, no. 5, pp. 501–505, 2005.
[3] L. Perez, M. R. Shurin, B. Collins, D. Kogan, I. L. Tourkova, and G. V. Shurin, “Comparative analysis of CD1a, S-100, CD83, and CD11c human dendritic cells in normal, premalignant, and malignant tissues,” Histol. Histopathol., vol. 20, no. 4, pp. 1165–1172, 2005.
[4] Y. Becker, “Anticancer role of dendritic cells (DC) in human and experimental cancers - A review,” Anticancer Research, vol. 12, no. 2. pp. 511–520, 1992.
[5] F. O. Nestle, G. Burg, J. Fäh, T. Wrone-Smith, and B. J. Nickoloff, “Human sunlight-induced basal-cell-carcinoma-associated dendritic cells are deficient in T cell co-stimulatory molecules and are impaired as antigen- presenting cells,” Am. J. Pathol., vol. 150, no. 2, pp. 641–651, 1997.
[6] S. Tsujitani, Y. Kakeji, A. Watanabe, S. Kohnoe, Y. Maehara, and K. Sugimachi, “Infiltration of dendritic cells in relation to tumor invasion and lymph node metastasis in human gastric cancer,” Cancer, vol. 66, no. 9, pp. 2012–2016, 1990.
[7] W. Yang and J. Yu, “Immunologic function of dendritic cells in esophageal cancer,” Digestive Diseases and Sciences, vol. 53, no. 7. Springer, pp. 1739–1746, 2008.
[8] H. Nomori, S. Watanabe, T. Nakajima, Y. Shimosato, and T. Kameya, “Histiocytes in nasopharyngeal carcinoma in relation to prognosis,” Cancer, vol. 57, no. 1, pp. 100–105, 1986.
[9] K. Ambe, M. Mori, and M. Enjoji, “S‐100 protein‐positive dendritic cells in colorectal adenocarcinomas. Distribution and relation to the clinical prognosis,” Cancer, vol. 63, no. 3, pp. 496–503, 1989.
[10] N. S. Katsenelson, G. V Shurin, S. N. Bykovskaia, J. Shogan, and M. R. Shurin, “Human small cell lung carcinoma and carcinoid tumor regulate dendritic cell maturation and function,” Mod. Pathol., vol. 14, no. 1, pp. 40–45, 2001.
[11] T. Oyama et al., “Vascular endothelial growth factor affects dendritic cell maturation through the inhibition of nuclear factor-kappa B activation in hemopoietic progenitor cells.,” J. Immunol., vol. 160, no. 3, pp. 1224–1232, 1998.
[12] P. Fang et al., “Immune cell subset differentiation and tissue inflammation,” Journal of Hematology and Oncology, vol. 11, no. 1. BioMed Central Ltd., 2018.
[13] M. B. Lutz and G. Schuler, “Immature, semi-mature and fully mature dendritic cells: Which signals induce tolerance or immunity?,” Trends in Immunology, vol. 23, no. 9. Trends Immunol, pp. 445–449, 2002.
[14] Z. Chen, X. Zhang, J. Xiang, and J. R. Gordon, “Analysis of the gene expression profiles of immature versus mature bone marrow-derived dendritic cells using DNA arrays,” Biochem. Biophys. Res. Commun., vol. 290, no. 1, pp. 66–72, 2002.
[15] M. C. Dieu et al., “Selective recruitment of immature and mature dendritic cells by distinct chemokines expressed in different anatomic sites,” J. Exp. Med., vol. 188, no. 2, pp. 373–386, 1998.
[16] E. Jörundsson, C. M. L. Press, and T. Landsverk, “Distribution of MHC-II and CD1 molecules in the skin of lambs and changes during experimentally-induced contact hypersensitivity,” Vet. Immunol. Immunopathol., vol. 74, no. 1–2, pp. 87–101, 2000.
[17] E. B. Bröcker, C. Reckenfeld, H. Hamm, D. J. Ruiter, and C. Sorg, “Macrophages in melanocytic naevi,” Arch. Dermatol. Res., vol. 284, no. 3, pp. 127–131, 1992.
[18] D. Garcia-Plata et al., “Immunophenotype analysis of dendritic cells and lymphocytes associated with cutaneous malignant melanomas,” Invasion and Metastasis, vol. 15, no. 3–4, pp. 125–134, 1995.
[19] K. Toriyama, K. D.-R. Wen, E. Paul, and A. J. Cochran, “Variations in the Distribution, Frequency, and Phenotype of Langerhans Cells During the Evolution of Malignant Melanoma of the Skin.,” J. Invest. Dermatol., vol. 100, no. 3, pp. 269S-273S, 1993.
[20] N. Mizumoto and A. Takashima, “CD1a and langerin: acting as more than Langerhans cell markers,” J. Clin. Invest., vol. 113, no. 5, pp. 658–660, 2004.
[21] S. W. Kashem, M. Haniffa, and D. H. Kaplan, “Antigen-presenting cells in the skin,” Annual Review of Immunology, vol. 35. Annual Reviews Inc., pp. 469–499, 2017.
