Comparison of Immunosuppressive and Immunomodulatory Cells in Keratoacanthoma and Cutaneous Squamous Cell Carcinoma

Abstract

An imbalance of immunosuppressive and immunomodulatory cells plays an important role in inhibiting the anti-tumour immune response in a tumour-bearing host. Among such cells, regulatory T cells (Tregs), together with immunosuppressive macrophages, such as CD163+ M2 macrophages, play roles in maintaining the tumour microenvironment. In contrast, interleukin-27 (IL-27) induces STAT1 and STAT3 activation, thus resulting in the enhancement of naive CD4 T-cell proliferation, the promotion of early Th1 differentiation, and the induction of the anti-tumour immune response. The purpose of this study was to investigate the involvement of immunosuppressive cells, such as Tregs and CD163+ macrophages, as well as immunomodulatory cells (i.e. IL-27-producing cells) in keratoacanthoma (KA) and invasive squamous cell carcinoma (SCC). We also examined the presence of CD3+ Foxp3+ Tregs cells in lesional skin from 10 patients with KA and 18 patients with SCC. Increased numbers of CD3+ Foxp3+ Tregs were observed in SCC compared with KA. In parallel with Tregs, higher numbers of CD163+ macrophages and MMP-9+ cells were detected only in SCC. In contrast, IL-27-producing cells were increased only in KA. In addition, the expression of pSTAT1 on tumour cells was observed only in KA. These findings suggest that the induction of immunosuppressive and immunomodulatory cells differs between KA and SCC.

Histogenesis of keratoacanthoma: histochemical and immunohistochemical study

“…7,47,48 There are several reports of differential expression of molecular markers, such as laminin-32, nuclear factor kappa B/p50, cortactin, glut-1, Bcl-x, beta-catenin, CD44, anti-P2 X7, K10, E-cadherin, transforming growth factor-a, peanut agglutinin, peanut lectin receptor, and carcinoembryonic antigen, in KAs and SCCs. 22,31,40,43,44,[49][50][51][52][53][54][55][56][57][58][59][60][61][62] KAs were consistently positive for K6, K10, and K14. K10 and K14 were observed in specialized cells within the ORS of the hair follicle and in the interfollicular epithelium.…”

Interleukin-27 inhibits foam cell formation by promoting macrophage ABCA1 expression through JAK2/STAT3 pathway

“…Regulation of ABCA1 expression impacts the reverse cholesterol transport (RCT) and foam cell formation [13][14][15]. In detail, IL-27 activates cellular signal pathway [16][17][18][19], and induction of anti-inflammatory immune responses [7,20]. Several studies reported a potential role of STAT molecules in the ABCA1 gene regulation [21,22].…”

Comparison of CD163+ CD206+ M2 Macrophages in the Lesional Skin of Bullous Pemphigoid and Pemphigus Vulgaris: The Possible Pathogenesis of Bullous Pemphigoid

“…Before the antigen retrieval procedure, we used 0.3% H 2 O 2 in methanol to inhibit endogenous peroxidase. The 10 cutaneous BP and PV samples were processed for single staining of IL-4, IL-13, pSTAT6, pSTAT1, CD163, CD206, CCL17, CCL18 and Foxp3, and developed with liquid permanent red (Dako A/S, Glostrup, Denmark) or with 3,3′-diaminobenzidine tetrahydrochloride (Wako Pure Chemical Industries, Osaka, Japan) as we previously reported [11]. …”