Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06126 (CD1a)
 2,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Topical 5-aminolevulinic acid-based photodynamic therapy (PDT) has produced complete response rates of >90% for nonmelanoma skin carcinomas, which are mostly human papillomavirus (HPV) negative. Using a similar treatment protocol, we observed a short-term response in only one third (10 of 32) of high-grade vulval intraepithelial neoplasia (VIN 2-3) lesions. Unifocal lesions were found more responsive than multifocal and pigmented lesions. Animal model studies have suggested that long-term PDT response involves an immune reaction in which CTLs play a crucial role. In this study, we have assessed: (a) HPV infection; (b) HLA expression; and (c) immune infiltrating cells in VIN biopsies from responders and nonresponders to determine whether these factors may limit response to topical 5-aminolevulinic acid-based PDT. Tissues from normal vulva (n = 9), vulval carcinoma (n = 11), and VIN (32 patients from which 19 pre- and 43 post-PDT biopsies were taken) were investigated for immune cell infiltration and HLA class I expression by immunohistochemistry and HPV infection by PCR. There was a greater likelihood of HPV positivity associated with a lack of response of VIN to PDT (P = 0.002), and VIN nonresponders were more likely to show HLA class I loss compared with responders (P = 0.030). HLA class I down-regulation was significantly greater in the carcinomas (82%, total loss) than the VIN (28%, 19%, total loss; and 9%, allele loss; P = 0.004). None of the cases with class I down-regulation responded to PDT, whereas 3 of 6 (50%) of cases that showed total class I loss subsequently developed superficial invasion. Compared with normal vulval skin, VIN lesions showed increased infiltration by CD4 (T-helper) and CD68 (macrophages) but not CD1a (Langerhans cells) or CD8 (CTLs). There was, however, a significant increase of CD8 infiltration in posttreatment VIN responders compared with nonresponders (P = 0.0001). These data clearly support the contention that high-risk HPV infection and lack of cell-mediated immunity may play a role in the observed poor response of lower genital lesions to topical PDT.
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PMID:Immunological and viral factors associated with the response of vulval intraepithelial neoplasia to photodynamic therapy. 1119 60

In this study, the expression patterns of Galectin-3 (Gal-3) and the frequency of infiltrating CD1a positive dendritic cells (DCs) were determined in 82 cases of vulvar tissues, consisting of normal squamous epithelia (NE, N = 10), vulvar condylomas (VC, N = 24), high grade vulvar intraepithelial neoplasias (HG-VIN, N = 26) of common type, and invasive keratinizing squamous cell carcinomas (SCC, N = 22) by a standard immunohistochemical method using monoclonal antibodies to investigate their differential expression in vulvar squamous dysplasia and infiltrating carcinomas with an emphasis on neoplastic transformation and progression. Gal-3 expression was cytoplasmic, nuclear or membranous in NE, VCs, and HG-VINs, with negative or weak and occasionally moderate reactivities. In SCCs, exclusively cytoplasmic staining patterns with moderate or strong reactivity in 59% of cases were observed (p < 0.0001, chi-square test); Gal-3 expression was not related with stage, grade, and recurrence. The frequency of CD1a positive DCs increased from NE and VCs to highest numbers in HG-VINs, was lowest in SCCs (p < 0.0001, ANOVA), and was not related with stage and grade, but with recurrence in SCCs (p = 0,048, t-test). This study indicates that qualitative and quantitative changes of Gal-3 immunoexpression and infiltration by CD1a positive DCs in vulvar NE, VCs, and HG-VIN lesions, respectively, compared with SCCs play a role in the development of an infiltrative phenotype, and may provide adjunctive criteria in the diagnosis of invasion of vulvar squamous epithelia.
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PMID:Galectin-3 and CD1a-positive dendritic cells are involved in the development of an invasive phenotype in vulvar squamous lesions. 1630 81

Recently, we reported on the efficacy of imiquimod for treatment of usual type vulvar intraepithelial neoplasia (uVIN). A histologic regression of uVIN to normal tissue was observed in 58% of patients. As success of treatment is related to clearance of high-risk human papilloma virus (HPV), the aim of our study was to assess differences in immune cell counts and in the expression of p16(INK4a) in VIN tissue before and after imiquimod treatment, in relation to HPV clearance and clinical response. Vulvar tissue samples taken prior to imiquimod treatment and 4 weeks after treatment were tested for the presence of HPV. Previously determined immune cell counts (CD1a, CD207, CD208, CD123/CD11c, CD94, CD4, CD8 and CD25/HLA-DR) in epidermis and dermis of 25 VIN patients and 19 healthy controls were completed with the counts for CD14 and CD68. The expression of p16(INK4a) was investigated by immunohistochemistry in 15 patients. Before imiquimod treatment, both HPV cleared and HPV noncleared patients showed mainly in the dermis significantly upregulated immune cell counts compared to healthy controls. However, in patients that cleared HPV and showed histologic regression already 4 weeks after imiquimod treatment, immune cell counts and p16(INK4a) expression were normalized. In conclusion, our data indicate that imiquimod-induced clearance of HPV results in normalization of counts for certain immune cells and is strongly correlated with histologic regression of the disease.
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PMID:Imiquimod-induced clearance of HPV is associated with normalization of immune cell counts in usual type vulvar intraepithelial neoplasia. 2135 Dec 62