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Thèse de Doctorat
DOI
https://doi.org/10.11606/T.5.2021.tde-08092021-141435
Document
Auteur
Nom complet
Gustavo Nunes Bento
Adresse Mail
Unité de l'USP
Domain de Connaissance
Date de Soutenance
Editeur
São Paulo, 2021
Directeur
Jury
Cernea, Claudio Roberto (Président)
Matos, Leandro Luongo de
Pai, Sara Isabel
Santos, André Bandiera de Oliveira
Titre en portugais
Expressão de PD1, PD-L1, PD-L2 e CD8+ em carcinomas escamocelulares cutâneos de alto risco em cabeça e pescoço
Mots-clés en portugais
Carcinoma de células escamosas
CD8+
Linfócitos de interstício tumoral
Microambiente tumoral.
Neoplasias cutâneas
Neoplasias de cabeça e pescoço
PD-1
PD-L1
PD-L2
Resumé en portugais
Objetivos: o carcinoma de células escamosas cutâneo (CEC) é o segundo câncer de pele mais comum entre os indivíduos de pele clara e é causado pela radiação UV. Os immune checkpoints, como PD-1 (Programmed Death) e seus ligantes, PD-L1 e PD-L2, são uma maneira eficaz de reativar a resposta imune antitumoral do hospedeiro em muitos tipos de câncer. O objetivo foi avaliar a presença do eixo PD-1: PD-L1 / PD-L2 e o infiltrado CD8+ associado no CEC de pele de cabeça e pescoço. Métodos: foram identificados 46 pacientes com CEC de alto risco. A coloração multiplex para PD-1, PD-L1, PD-L2 e CD8 foi realizada e as imagens foram capturadas por um microscópio de epifluorescência. As positividades PD-1, PD-L1 e PD-L2 foram pontuadas com base nos valores de corte determinados como > 1%, > 20% e > 50%. A curva ROC foi aplicada para definir o valor de corte estatisticamente mais significativo para recorrência e óbito. Resultados: todos os resultados abaixo se referem à expressão em > 1% das células. A expressão de PD-1, PD-L1 e PD-L2 foi encontrada em 80,4% (37 de 46), 84,8% (39 de 46), 47,8% (22 de 46) pacientes, respectivamente. PD-1 / PD-L1, PD-1 / PD-L2 e PD-L1 / PD-L2 colocalizados em 80,4% (37 de 46), 45,7% (21 de 46) e 47,8% (22 de 46) pacientes, respectivamente. Todos os pacientes apresentaram infiltração de CD8+ em algum grau. Nesse infiltrado, PD-1 / PD-L1, PD-1 / PD-L2 e PD-1 / PD-L1 / PD-L2 foram colocalizados em 97,8% (45 de 46), 82,6% (38 de 46) e 82,6% (38 de 46) pacientes, respectivamente. Conclusão: o eixo PD-1: PDL1 / PD-L2 é muito expresso no CEC de pele. Os presentes achados apoiam a investigação do bloqueio dessa via nesse tipo de tumor.
Titre en anglais
PD-1, PD-L1, PD-L2 and CD8 expression in advanced head and neck cutaneous squamous cell carcinomas
Mots-clés en anglais
Carcinoma
CD8+
Head and neck neoplasms
Lymphocytes
PD-1
PD-L1
PD-L2
Skin neoplasms
squamous cell
Tumor microenvironment
tumor-infiltrating
Resumé en anglais
Objectives: cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer among caucasians and is caused by UV radiation. Blockade of immune checkpoint axes, such as programmed cell death 1 (PD1) and its ligands, PD-L1 and PD-L2, is an effective way to reactivate the host anti-tumor immune response across many cancer types. Our aim was to assess the presence of the PD-1: PD-L1/PD-L2 axis and associated CD8+ infiltrate in cSCC of the head and neck. Methods: 46 patients with high-risk cSCC were identified. Multiplex staining for PD-1, PD-L1, PD-L2, and CD8 was performed and images were captured by an epifluorescence microscope. PD1, PD-L1, and PD-L2 positivity were scored based on cutoff values of > 1%, > 20% and > 50%. ROC curve method was applied to define the most statistically significant cutoff value for recurrence and death. Results: all results below refer to the expression in > 1% of the cells. PD-1, PD-L1 and PD-L2 expression was found in 80.4% (37 of 46), 84.8% (39 of 46), 47.8% (22 of 46) patients, respectively. PD-1/PD-L1, PD-1/PD-L2 and PD-L1/PD-L2 co-localized in 80.4% (37 of 46), 45.7% (21 of 46) and 47.8% (22 of 46) patients, respectively. All patients had CD8+ infiltration. In this infiltrated, PD-1/PD-L1, PD-1/PD-L2 and PD-1/PD-L1/PD-L2 co-localized in 97.8% (45 of 46), 82.6% (38 of 46) and 82.6% (38 of 46) patients, respectively. Conclusion: the PD-1:PD-L1/PD-L2 axis is highly activated in cSCC. Our findings support further studies on the use of pathway blockade in this tumor type.
 
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Date de Publication
2021-09-20
 
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