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  1 / 1085 MEDLINE  
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PMID:29212853
Autor:Simon S; Vignard V; Varey E; Parrot T; Knol AC; Khammari A; Gervois N; Lang F; Dreno B; Labarriere N
Endereço:CRCINA, INSERM, Université d'Angers, Université de Nantes, Nantes, France.
Título:Emergence of High-Avidity Melan-A-Specific Clonotypes as a Reflection of Anti-PD-1 Clinical Efficacy.
Fonte:Cancer Res; 77(24):7083-7093, 2017 Dec 15.
ISSN:1538-7445
País de publicação:United States
Idioma:eng
Resumo:Therapeutic strategies using anti-PD-1-blocking antibodies reported unparalleled effectiveness for melanoma immunotherapy, but deciphering immune responses modulated by anti-PD-1 treatment remains a crucial issue. Here, we analyzed the composition and functions of the large Melan-A-specific T-cell repertoire in the peripheral blood of 9 melanoma patients before and after 2 months of treatment with anti-PD-1. We observed amplification of Melan-A-specific Vß subfamilies undetectable before therapy (thereafter called emerging Vß subfamilies) in responding patients, with a predominant expansion in patients with a complete response. These emerging Vß subfamilies displayed a higher functional avidity for their cognate antigen than Vß subfamilies not amplified upon anti-PD-1 therapy and could be identified by a sustained coexpression of PD-1 and TIGIT receptors. Thus, in addition to the emergence of neoantigen-specific T cells previously documented upon anti-PD-1 therapy, our work describes the emergence of high-avidity Melan-A-specific clonotypes as a surrogate marker of treatment efficacy. .
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (Antibodies, Monoclonal); 0 (Antigens, Neoplasm); 0 (MART-1 Antigen); 0 (PDCD1 protein, human); 0 (Programmed Cell Death 1 Receptor)


  2 / 1085 MEDLINE  
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PMID:28884480
Autor:Faure F; Jouve M; Lebhar-Peguillet I; Sadaka C; Sepulveda F; Lantz O; Berre S; Gaudin R; Sánchez-Ramón S; Amigorena S
Endereço:Institut Curie, PSL Research University, INSERM U932, Paris, 75005, France.
Título:Blood monocytes sample MelanA/MART1 antigen for long-lasting cross-presentation to CD8 T cells after differentiation into dendritic cells.
Fonte:Int J Cancer; 142(1):133-144, 2018 Jan 01.
ISSN:1097-0215
País de publicação:United States
Idioma:eng
Resumo:Human blood monocytes are very potent to take up antigens. Like macrophages in tissue, they efficiently degrade exogenous protein and are less efficient than dendritic cells (DCs) at cross-presenting antigens to CD8 T cells. Although it is generally accepted that DCs take up tissue antigens and then migrate to lymph nodes to prime T cells, the mechanisms of presentation of antigens taken up by monocytes are poorly documented so far. In the present work, we show that monocytes loaded in vitro with MelanA long peptides retain the capacity to stimulate antigen-specific CD8 T cell clones after 5 days of differentiation into monocytes-derived dendritic cells (MoDCs). Tagged-long peptides can be visualized in electron-dense endocytic compartments distinct from lysosomes, suggesting that antigens can be protected from degradation for extended periods of time. To address the pathophysiological relevance of these findings, we screened blood monocytes from 18 metastatic melanoma patients and found that CD14 monocytes from two patients effectively activate a MelanA-specific CD8 T cell clone after in vitro differentiation into MoDCs. This in vivo sampling of tumor antigen by circulating monocytes might alter the tumor-specific immune response and should be taken into account for cancer immunotherapy.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (MART-1 Antigen); 0 (MLANA protein, human)


  3 / 1085 MEDLINE  
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PMID:28664991
Autor:Li H; Shao S; Cai J; Burner D; Lu L; Chen Q; Minev B; Ma W
Endereço:Department of Basic Medicine, Huzhou University School of Medicine, Huzhou, Zhejiang, China.
Título:Artificial human antigen-presenting cells are superior to dendritic cells at inducing cytotoxic T-cell responses.
Fonte:Immunology; 152(3):462-471, 2017 Nov.
ISSN:1365-2567
País de publicação:England
Idioma:eng
Resumo:Peptide recognition through the MHC class I molecule by cytotoxic T lymphocytes (CTLs) leads to the killing of cancer cells. A potential challenge for T-cell immunotherapy is that dendritic cells (DCs) are exposed to the MHC class I-peptide complex for an insufficient amount of time. To improve tumour antigen presentation to T cells and thereby initiate a more effective T-cell response, we generated artificial antigen-presenting cells (aAPCs) by incubating human immature DCs (imDCs) with poly(lactic-co-glycolic) acid nanoparticles (PLGA-NPs) encapsulating tumour antigenic peptides, followed by maturation with lipopolysaccharide. Tumour antigen-specific CTLs were then induced using either peptide-loaded mature DCs (mDCs) or aAPCs, and their activities were analysed using both ELISpot and cytotoxicity assays. We found that the aAPCs induced significantly stronger tumour antigen-specific CTL responses than the controls, which included both mDCs and aAPCs loaded with empty nanoparticles. Moreover, frozen CTLs that were generated by exposure to aAPCs retained the capability to eradicate HLA-A2-positive tumour antigen-bearing cancer cells. These results indicated that aAPCs are superior to DCs when inducing the CTL response because the former are capable of continuously presenting tumour antigens to T cells in a sustained manner. The development of aAPCs with PLGA-NPs encapsulating tumour antigenic peptides is a promising approach for the generation of effective CTL responses in vitro and warrants further assessments in clinical trials.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (BIRC5 protein, human); 0 (Cancer Vaccines); 0 (Delayed-Action Preparations); 0 (Inhibitor of Apoptosis Proteins); 0 (Lipopolysaccharides); 0 (MART-1 Antigen); 0 (MLANA protein, human); 0 (Peptide Fragments); 0 (polylactic acid-polyglycolic acid copolymer); 26009-03-0 (Polyglycolic Acid); 33X04XA5AT (Lactic Acid)


  4 / 1085 MEDLINE  
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PMID:28322032
Autor:Inouye CM; Cimino-Mathews A; Eisner D; Rosenthal DL; VandenBussche CJ
Endereço:Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
Título:Fine-needle aspiration of metastatic melanoma presenting as bilateral breast cysts.
Fonte:Diagn Cytopathol; 45(5):446-451, 2017 May.
ISSN:1097-0339
País de publicação:United States
Idioma:eng
Resumo:Melanoma is the second most common non-hematopoietic malignancy after carcinomas to metastasize to the breast and often appears as a well-circumscribed, dense nodule on imaging. Although metastatic lesions presenting as bilateral cysts have been reported, this presentation is not common and may mimic benign breast cysts. We present a challenging case of metastatic melanoma presenting as bilateral breast cysts with spindled cytomorphology in a patient with a history of mammary carcinoma. Discordance between the spindled cytomorphology and the morphology of the core biopsy, which was similar to the patient's primary breast cancer, allowed for entertainment of other tumors and disease processes. Confirmatory immunostaining of the cytology material with HMB-45 was important to establish the diagnosis of metastatic melanoma. Diagn. Cytopathol. 2017;45:446-451. © 2017 Wiley Periodicals, Inc.
Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE
Nome de substância:0 (Biomarkers, Tumor); 0 (HMB-45 protein, human); 0 (MART-1 Antigen); 0 (Melanoma-Specific Antigens); 0 (S100 Proteins)


  5 / 1085 MEDLINE  
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PMID:28301898
Autor:Lee SY; Kim BH
Endereço:Department of Pathology, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea.
Título:Epithelioid angiomyolipoma of the liver: a case report.
Fonte:Clin Mol Hepatol; 23(1):91-94, 2017 Mar.
ISSN:2287-285X
País de publicação:Korea (South)
Idioma:eng
Resumo:Epithelioid angiomyolipoma (EAML) of liver is a rare neoplasm. Hepatic EAML is often misdiagnosed as other neoplasms such as hepatocellular carcinoma due to non-specific clinical and radiologic features. The morphologic features under microscope and immunohistochemistry staining profile are important in the diagnosis EAML. Here, we report a case of 52-year-old man who found 1.2 cm mass in liver by routine checkup. On the impression of hepatocellular carcinoma, lateral sectionectomy of the liver was done. Microscopically, the tumor is composed of predominant epithelioid cells with vascular component and foamy cells. These cells were positive for HMB45, MelanA, and smooth muscle actin and negative for epithelial membrane antigen. The final diagnosis was hepatic EAML.
Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE
Nome de substância:0 (HMB-45 protein, human); 0 (MART-1 Antigen); 0 (MLANA protein, human); 0 (Melanoma-Specific Antigens)


  6 / 1085 MEDLINE  
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PMID:28288506
Autor:Son HJ; Kang DW; Kim JH; Han HY; Lee MK
Endereço:Department of Pathology, Eulji University School of Medicine, Daejeon, Korea.
Título:Hepatic perivascular epithelioid cell tumor (PEComa): a case report with a review of literatures.
Fonte:Clin Mol Hepatol; 23(1):80-86, 2017 Mar.
ISSN:2287-285X
País de publicação:Korea (South)
Idioma:eng
Resumo:Hepatic perivascular epithelioid cell tumors (PEComas) are very rare. We report a primary hepatic PEComa with a review of the literature. A 56-year-old women presented with a nodular mass detected during the management of chronic renal failure and chronic hepatitis C. Diagnostic imaging studies suggested a nodular hepatocellular carcinoma in segment 5 of the liver. The patient underwent partial hepatectomy. A brown-colored expansile mass measuring 3.2×3.0 cm was relatively demarcated from the surrounding liver parenchyma. The tumor was mainly composed of epithelioid cells that were arranged in a trabecular growth pattern. Adipose tissue and thick-walled blood vessels were minimally identified. A small amount of extramedullary hematopoiesis was observed in the sinusoidal spaces between tumor cells. Tumor cells were diffusely immunoreactive for human melanoma black 45 (HMB45) and Melan A, focally immunoreactive for smooth muscle actin, but not for hepatocyte specific antigen (HSA).
Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE; REVIEW
Nome de substância:0 (ACTA2 protein, human); 0 (Actins); 0 (Antibodies, Viral); 0 (HMB-45 protein, human); 0 (MART-1 Antigen); 0 (MLANA protein, human); 0 (Melanoma-Specific Antigens)


  7 / 1085 MEDLINE  
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PMID:28195103
Autor:Kodiatte TA; George SV; Chacko RT; Ramakrishna B
Endereço:Department of General Pathology, Christian Medical College, Vellore, Tamil Nadu, India.
Título:Malignant melanocytic neoplasm of pancreas with liver metastasis: Is it malignant melanoma or clear cell sarcoma?
Fonte:Indian J Pathol Microbiol; 60(1):102-104, 2017 Jan-Mar.
ISSN:0974-5130
País de publicação:India
Idioma:eng
Resumo:Malignant melanocytic neoplasm, usually seen in soft tissues, is rare in a visceral location and presents as a diagnostic dilemma. We present a case of pancreatic malignant melanocytic neoplasm with liver metastasis. A 58-year-old man presented with left upper abdominal swelling and loss of appetite. Imaging revealed a large mass arising from the pancreatic tail, and this was diagnosed as malignant neoplasm with melanocytic differentiation on biopsy with the possible differentials of malignant melanoma, clear cell sarcoma (CCS), and perivascular epithelioid cell neoplasm. The patient underwent distal pancreatectomy and splenectomy for the same. Follow-up imaging 6 months later showed a metastatic liver lesion, for which he also underwent a liver resection. BRAF mutational analysis was found to be negative. Both CCS and malignant melanoma have similar morphological features and melanocytic differentiation, but each harbors a distinct genetic background. Differentiation of both has diagnostic and therapeutic implications.
Tipo de publicação: CASE REPORTS
Nome de substância:0 (Biomarkers, Tumor); 0 (HMB-45 protein, human); 0 (MART-1 Antigen); 0 (Melanoma-Specific Antigens); 0 (S100 Proteins)


  8 / 1085 MEDLINE  
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PMID:28161440
Autor:Reddy HS; Keene CD; Chang SH; Jian-Amadi A; Cimino PJ
Endereço:Ophthalmic Plastic and Reconstructive Surgery, New York Eye and Ear Infirmary of Mount Sinai, New York, NY, United States.
Título:Immunohistochemical profiling including beta-catenin in conjunctival melanocytic lesions.
Fonte:Exp Mol Pathol; 102(2):198-202, 2017 Apr.
ISSN:1096-0945
País de publicação:Netherlands
Idioma:eng
Resumo:Conjunctival melanocytic lesions encompass a group of clinically diverse, benign to malignant, neoplasms that may contain overlapping histopathological features, making definitive diagnosis challenging in some cases. In this series, we compared multiple immunohistochemical (IHC) markers in 11 conjunctival nevi, 10 primary acquired melanosis (PAM) lesions, and 11 conjunctival melanomas. Immunostains included the melanocytic markers HMB-45 and Melan-A, as well as the proliferative marker Ki-67. Loss of beta-catenin expression has been associated with more aggressive clinical disease in cutaneous melanoma, but its status in conjunctival melanocytic lesions is not known, therefore we incorporated beta-catenin immunohistochemical staining in our study. In this series, conjunctival melanomas had a higher Ki-67 proliferative index and HMB-45 immunoreactivity than did PAM lesions and conjunctival nevi (P<0.001). Melan-A was highly expressed in all 3 groups. Beta-catenin was more strongly expressed in melanomas and nevi than in PAM (P<0.001). There was high inter-grader reliability (Kappa=0.53). Overall, IHC labeling of HMB-45 and Ki-67 is increased in conjunctival melanomas compared to PAM or conjunctival nevi. Beta-catenin, an IHC marker previously unstudied in conjunctival melanocytic lesions, is not preferentially expressed in benign lesions and may play a different role in conjunctival atypia than it does in cutaneous melanoma.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (CTNNB1 protein, human); 0 (Genetic Markers); 0 (HMB-45 protein, human); 0 (Ki-67 Antigen); 0 (MART-1 Antigen); 0 (Melanoma-Specific Antigens); 0 (beta Catenin)


  9 / 1085 MEDLINE  
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PMID:28160456
Autor:Lau RP; Chiaffarano J; Alexander M; Octavius J; Azar O; Shi Y; Yee-Chang M
Endereço:Department of Pathology, New York University School of Medicine, New York, New York.
Título:Primary anorectal mucosal melanoma detected by anorectal cytology.
Fonte:Diagn Cytopathol; 45(5):452-455, 2017 May.
ISSN:1097-0339
País de publicação:United States
Idioma:eng
Resumo:The detection of primary anorectal melanoma on anal cytology is a rare and challenging diagnosis. We report a case where anorectal cytology showed isolated malignant cells with oval nuclei, prominent nucleoli, and elongated wispy cytoplasmic projections. There was no evidence of squamous dysplasia or melanin pigment identified. To the best of our knowledge, this is the first reported case of a primary anorectal melanoma detected in anorectal cytology. Detection of malignancies other than squamous cell carcinoma can be seen on anorectal cytology and should be considered when there is no evidence of anal intraepithelial neoplasia. Diagn. Cytopathol. 2017;45:452-455. © 2017 Wiley Periodicals, Inc.
Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE
Nome de substância:0 (Biomarkers, Tumor); 0 (MART-1 Antigen); 0 (S100 Proteins)


  10 / 1085 MEDLINE  
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PMID:28139264
Autor:Shin TM; Shaikh WR; Etzkorn JR; Sobanko JF; Margolis DJ; Gelfand JM; Chu EY; Elenitsas R; Miller CJ
Endereço:Department of Dermatology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: Thuzar.Shin@uphs.upenn.edu.
Título:Clinical and pathologic factors associated with subclinical spread of invasive melanoma.
Fonte:J Am Acad Dermatol; 76(4):714-721, 2017 Apr.
ISSN:1097-6787
País de publicação:United States
Idioma:eng
Resumo:BACKGROUND: Indications to treat invasive melanoma with Mohs micrographic surgery (MMS) or analogous techniques with exhaustive microscopic margin assessment have not been defined. OBJECTIVE: Identify clinical and histologic factors associated with subclinical spread of invasive melanoma. METHODS: This retrospective, cross-sectional study evaluated 216 invasive melanomas treated with MMS and melanoma antigen recognized by T cells 1 immunostaining. Logistic regression models were used to correlate clinicopathologic risk factors with subclinical spread and construct a count prediction model. RESULTS: Risk factors associated with subclinical spread by multivariate analysis included tumor localization on the head and neck (OR 3.28, 95% confidence interval [CI] 1.16-9.32), history of previous treatment (OR 4.18, 95% CI 1.42-12.32), age ≥65 (OR 4.45, 95% CI 1.29-15.39), and ≥1 mitoses/mm (OR 2.63, 95% CI 1.01-6.83). Tumor thickness and histologic subtype were not associated with subclinical spread. The probability of subclinical spread increased per number of risk factors, ranging from 9.22% (95% CI 2.57%-15.86%) with 1 factor to 80.32% (95% CI 68.13%-92.51%) with 5 factors. LIMITATIONS: This study was conducted at a single academic institution with a small study population using a retrospective study design that was subject to potential referral bias. CONCLUSION: Clinical and histologic factors identify invasive melanomas that are at increased risk for subclinical spread and might benefit from MMS or analogous techniques prior to reconstruction.
Tipo de publicação: JOURNAL ARTICLE
Nome de substância:0 (MART-1 Antigen)



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