Tumour-infiltrating Langerhans cells in non-melanoma skin cancer, a clinical and immunohistochemical study

Maraee, Alaa Hassan; Antar, Azza Gaber; Gadallah, Maram Mashhour; Abdou, Asmaa Gaber

doi:10.3332/ecancer.2020.1045

Cited by 5 publications

(7 citation statements)

References 30 publications

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“…Moreover, the percentages of LCs are higher in healthy epidermis when compared to the adjacent epidermis, flanking the tumoral tissue, and to the intratumoral tissue. Furthermore, the percentages of LCs are higher in BCC than in SCC [56]. In contrast, our data show very few LCs within the tumoral mass of BCC (Figure 3), as opposed to SCC, where LCs are relatively abundant (Figure 4).…”

Section: Skin Cancerscontrasting

confidence: 68%

Langerhans Cells—Revising Their Role in Skin Pathologies

Neagu

Constantin

Jugulete

et al. 2022

JPM

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Langerhans cells (LCs) constitute a cellular immune network across the epidermis. Because they are located at the skin barrier, they are considered immune sentinels of the skin. These antigen-presenting cells are capable of migrating to skin draining lymph nodes to prime adaptive immune cells, namely T- and B-lymphocytes, which will ultimately lead to a broad range of immune responses. Moreover, LCs have been shown to possess important roles in the anti-cancer immune responses. Indeed, the literature nicely highlights the role of LCs in melanoma. In line with this, LCs have been found in melanoma tissues where they contribute to the local immune response. Moreover, the immunogenic properties of LCs render them attractive targets for designing vaccines to treat melanoma and autoimmune diseases. Overall, future studies will help to enlarge the portfolio of immune properties of LCs, and aid the prognosis and development of novel therapeutic approaches to treating skin pathologies, including cancers.

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Section: Skin Cancerscontrasting

confidence: 68%

Langerhans Cells—Revising Their Role in Skin Pathologies

Neagu

Constantin

Jugulete

et al. 2022

JPM

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“…To our knowledge, LC count was not investigated before in BCC of XP patients; however, it was reported to be of lower density with morphologic changes in the BCC lesions of normal individuals compared with normal skin. 9,11,[22][23][24][25] Furthermore, UV exposure not only affects the LCs numbers but also affects their antigen-presenting capacity. UV-irradiated LCs present antigens to Th2 cells, but fail to activate Th1 cells.…”

Section: Discussionmentioning

confidence: 99%

“…These data explain the results proven in the present study in which the LCs count at the 3 different areas (intratumoral, peritumoral, and perilesional epidermis) were of significantly lower mean values in XP patients compared with non-XP controls. To our knowledge, LC count was not investigated before in BCC of XP patients; however, it was reported to be of lower density with morphologic changes in the BCC lesions of normal individuals compared with normal skin 9,11,22–25…”

Section: Discussionmentioning

confidence: 99%

Basal Cell Carcinoma in Xeroderma Pigmentosa: Reduced CD1a Expression as a Sensitive Predictor of Recurrence

Hanbuli

Sari

Dawoud

2023

Applied Immunohistochemistry &Amp; Molecular Morphology

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Xeroderma pigmentosa (XP) is a rare genetic disorder that is characterized by defective DNA repair after ultraviolet induced damage with a great tendency for recurrent cutaneous malignancies including basal cell carcinoma (BCC). BCC is frequently linked to impaired local immune response with a major role played by Langerhans cells (LCs). The current study aims at investigating LCs in BCC specimens of XP and non-XP patients, in a trial to study its possible impact on tumor recurrence. It included 48 retrospective cases of primary facial BCC (18 for XP patients and 30 for non-XP controls). Each group was subdivided, based on the 5 years follow-up data, into recurrent and non-recurrent BCC groups. LCs were assessed immunohistochemically using the sensitive marker; CD1a. Results showed significantly reduced LCs count (intratumoral, peritumoral, and in perilesional epidermis) in XP patients compared with non-XP controls (P˂0.001 for all). Intratumoral (P=0.008), peritumoral (P=0.005), and perilesional epidermal (P=0.02) LCs mean values were significantly lower in recurrent versus non-recurrent BCC specimens. Also, within each group (XP and controls), LCs were of significantly lower means in recurrent versus non-recurrent cases (P≤0.001 for all). Regarding recurrent BCC cases, peritumoral LCs showed a significant positive correlation with 1ry BCC duration (P=0.05). Also, intratumoral and peritumoral LCs correlated positively with BCC relapse interval (P=0.04 for both). Among non-XP controls, periocular tumors had the least LCs count (22.00±3.56), whereas tumors located in the rest of the face had the greatest count (29.00±0.00) (P=0.02). Sensitivity and specificity of LCs to predict BCC recurrence in XP patients reached 100% in intartumoral area and perilesional epidermis when cutoff points were less than 9.5 and 20.5, respectively. In conclusion; reduced LC count in primary BCC specimens of XP patients and also in normal subjects could help to predict its recurrence. Thus, it might be identified as a risk factor for relapse to apply new strict therapeutic and preventive measures. This presents new avenue for the immunosurveillance against skin cancer relapse. However, being the first study to investigate that link in XP patients recommends further research to confirm.

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“…Similar to LC in mice, human LC reside in the basal and supra-basal layers of the epidermis, where they form a dense network of first-line defense against invading pathogens. A recent study compared LC frequencies in 41 human non-melanoma tumor lesions and 16 healthy control tissues, revealing significantly decreased LC frequencies in tumor tissue and adjacent epidermis overlying malignant tissue compared to healthy skin; additionally, squamous cell carcinoma (SCC) lesions showed a more dramatic decrease of LC than that of basal cell carcinoma (BCC) lesions [95]. Consistent with this report, a systematic review of available nonmelanoma skin cancer-related studies was performed and quantitatively assessed LC in nonmelanoma skin cancers and identified an overall trend towards slightly higher numbers of LC in BCC than in SCC lesions, although there were discrepancies between individual studies [96].…”

Section: Langerhans Cells In Skin Cancer Development and Progressionmentioning

confidence: 99%

The Roles of Skin Langerhans Cells in Immune Tolerance and Cancer Immunity

et al. 2022

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Langerhans cells (LC) are a unique population of tissue-resident macrophages with dendritic cell (DC) functionality that form a network of cells across the epidermis of the skin. Their location at the skin barrier suggests an important role for LC as immune sentinels at the skin surface. The classification of LC as DC over the past few decades has driven the scientific community to extensively study how LC function as DC-like cells that prime T cell immunity. However, LC are a unique type of tissue-resident macrophages, and recent evidence also supports an immunoregulatory role of LC at steady state and during specific inflammatory conditions, highlighting the impact of cutaneous environment in shaping LC functionality. In this mini review, we discuss the recent literature on the immune tolerance function of LC in homeostasis and disease conditions, including malignant transformation and progression; as well as LC functional plasticity for adaption to microenvironmental cues and the potential connection between LC population heterogeneity and functional diversity. Future investigation into the molecular mechanisms that LC use to integrate different microenvironment cues and adapt immunological responses for controlling LC functional plasticity is needed for future breakthroughs in tumor immunology, vaccine development, and treatments for inflammatory skin diseases.

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Tumour-infiltrating Langerhans cells in non-melanoma skin cancer, a clinical and immunohistochemical study

Cited by 5 publications

References 30 publications

Langerhans Cells—Revising Their Role in Skin Pathologies

Langerhans Cells—Revising Their Role in Skin Pathologies

Basal Cell Carcinoma in Xeroderma Pigmentosa: Reduced CD1a Expression as a Sensitive Predictor of Recurrence

The Roles of Skin Langerhans Cells in Immune Tolerance and Cancer Immunity

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