Local immune response in basal cell carcinoma: Characterization by transmission electron microscopy and monoclonal anti-T6 antibody

Murphy, Gëorge F.; Krusinski, Paul A.; Myzak, Lydia A.; Ershler, William B.

doi:10.1016/s0190-9622(83)70052-6

Cited by 47 publications

(16 citation statements)

References 23 publications

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“…3,9 Increased numbers of CD4 + T cells surrounding the BCC infiltrating tumor island in the dermis have been observed after intralesional IFN-␣ therapy. [10][11][12] It has also been shown previously that the number of antigenpresenting cells (APC) expressing HLA-DR and CD1a is reduced in BCC, compared with normal human skin. 13 It is therefore likely that IFN-␣ therapy may render local APC more effective in triggering the immune response against tumor cells.…”

Section: Introductionmentioning

confidence: 87%

Liposome-mediated gene transfer into human basal cell carcinoma

et al. 1999

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Section: Introductionmentioning

confidence: 87%

Liposome-mediated gene transfer into human basal cell carcinoma

et al. 1999

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“…Langerhans cells are known to be one of the antigen presenting cells for T lymphocytes. They play a pivotal role in the presentation of tumorassociated antigens in neoplastic tissue, thereby facilitating T cell-mediated antitumoral immune responses [107][108][109]. The decreased Langerhans cells in As-BD lesions implied an impaired immune function on the lesional epidermis itself.…”

Section: Immunological Dysfunction In Arsenic-induced Skin Cancermentioning

confidence: 99%

Arsenic Carcinogenesis in the Skin

2006

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SummaryChronic arsenic poisoning is a world public health issue. Long-term exposure to inorganic arsenic (As) from drinking water has been documented to induce cancers in lung, urinary bladder, kidney, liver and skin in a dose-response relationship. Oxidative stress, chromosomal abnormality and altered growth factors are possible modes of action in arsenic carcinogenesis. Arsenic tends to accumulate in the skin. Skin hyperpigmentation and hyperkeratosis have long been known to be the hallmark signs of chronic As exposure. There are significant associations between these dermatological lesions and risk of skin cancer. The most common arsenic-induced skin cancers are Bowen's disease (carcinoma in situ), basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Arsenic-induced Bowen's disease (As-BD) is able to transform into invasive BCC and SCC. Individuals with As-BD are considered for more aggressive cancer screening in the lung and urinary bladder. As-BD provides an excellent model for studying the early stages of chemical carcinogenesis in human beings. Arsenic exposure is associated with G2/M cell cycle arrest and DNA aneuploidy in both cultured keratinocytes and As-BD lesions. These cellular abnormalities relate to the p53 dysfunction induced by arsenic. The characteristic clinical figures of arsenic-induced skin cancer are: (i) occurrence on sun-protected areas of the body; (ii) multiple and recrudescent lesions. Both As and UVB are able to induce skin cancer. Arsenic treatment enhances the cytotoxicity, mutagenicity and clastogenicity of UV in mammalian cells. Both As and UVB induce apoptosis in keratinocytes by caspase-9 and caspase-8 signaling, respectively. Combined UVB and As treatments resulted in the antiproliferative and proapoptotic effects by stimulating both caspase pathways in the keratinocytes. UVB irradiation inhibited mutant p53 and ki-67 expression, as well as increased in the number of apoptotic cells in As-BD lesions which resulted in an inhibitory effect on proliferation. As-UVB interaction provides a reasonable explanation for the rare occurrences of arsenical cancer in the sun-exposed skin. The multiple and recurrent skin lesions are associated with cellular immune dysfunction in chronic arsenism. A decrease in peripheral CD4+ cells was noticed in the inhabitants of arsenic exposure areas. There was a decrease in the number of Langerhans cells in As-BD lesion which results in an impaired immune function on the lesional sites. Since CD4+ cells are the target cell affected by As, the interaction between CD4+ cells and epidermal keratinocytes under As affection might be closely linked to the pathogenesis of multiple occurrence of arsenic-induced skin cancer. In this

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“…Our previous studies showed that arsenic induced apoptosis of peripheral CD4þ cells from normal subjects via tumor necrosis factor (TNF)-a and tumor necrosis factor receptor 1 (TNF-R1) pathway (13). Since CD4þ cell is a potent regulator for effective antitumor immunity (14,15), the compromised CD4þ cell integrity has important implications. More specifically, tumor surveillance is initiated by CD4þ cell-mediated antigen-presenting process, which provides the second signals for the effector phase of antitumor response (16,17).…”

Section: Introductionmentioning

confidence: 99%

Differential effects of arsenic on cutaneous and systemic immunity: focusing on CD4+ cell apoptosis in patients with arsenic-induced Bowen's disease

Liao

Lan

et al. 2009

Carcinogenesis

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Bowen's disease (BD), a carcinoma in situ of the skin, has been identified as an early lesion in arsenic carcinogenesis. Patients with arsenic-induced Bowen's disease (As-BD) showed both cutaneous and systemic immune dysfunctions. We set out to evaluate the interactions between keratinocytes and lymphocytes in the context of As-BD carcinogenesis. Our results showed that As-BD lesions demonstrated a significant dermal CD41 cell, an essential regulator of proper tumor immunity, undergoing apoptosis. In addition, it was found that the As-BD patients have lower percentage of peripheral CD41 cells as compared with control subjects. However, the CD41 cells from As-BD patients were less susceptible to arsenic-induced apoptosis, due to reduced tumor necrosis factor receptor 1 expression. Interestingly, arsenic was found to induce Fas expression on CD41 cells and increase the soluble Fas ligand (sFasL) production from keratinocytes. This sFasLcontaining keratinocyte supernatant was able to induce comparable CD41 cell apoptosis for both patients and controls. Using immunofluorescent staining, increased FasL was observed in keratinocytes of As-BD lesions and Fas was expressed among infiltrating CD41 cells. Our findings suggested that systemically, the percentage of CD41 cells was decreased in the peripheral blood of As-BD patients. These residual CD41 cells were less susceptible to arsenic-induced apoptosis. However, once infiltrated into the As-BD lesions, the selective CD41 cell apoptosis might be mediated by FasL from keratinocytes. This additional tumoranti-immune phenomenon present in the cutaneous environment provides a reasonable explanation for frequent occurrence of arsenic cancers in the skin.

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Local immune response in basal cell carcinoma: Characterization by transmission electron microscopy and monoclonal anti-T6 antibody

Cited by 47 publications

References 23 publications

Liposome-mediated gene transfer into human basal cell carcinoma

Liposome-mediated gene transfer into human basal cell carcinoma

Arsenic Carcinogenesis in the Skin

Differential effects of arsenic on cutaneous and systemic immunity: focusing on CD4+ cell apoptosis in patients with arsenic-induced Bowen's disease

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