Banca de DEFESA: MARIA LUIZA DINIZ DE SOUSA LOPES

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
DISCENTE : MARIA LUIZA DINIZ DE SOUSA LOPES
DATA : 30/01/2018
HORA: 08:30
LOCAL: AUDITÓRIO DO DEPARTAMENTO DE ODONTOLOGIA DA UFRN
TÍTULO:

 IMMUNE RESPONSE AND EVASION MECHANISMS IN LIP CARCINOGENESIS: AN IMMUNOHISTOCHEMICAL STUDY

PALAVRAS-CHAVES:

Squamous cell carcinoma; Cheilitis; Lip neoplasms; Immune Evasion; Immunologic cytotoxicity; Immunohistochemistry

PÁGINAS: 95
GRANDE ÁREA: Ciências da Saúde
ÁREA: Odontologia
RESUMO:

Immune surveillance, mainly mediated by CD8 + T lymphocytes, gives the human body the ability to recognize and destroy malignant or altered cells. However, through immunosuppressive strategies, such as the signaling pathways of the programmed cell death ligand-1 (PD-L1) and human leukocyte antigen-G (HLA-G), these mutated cells often escape the antitumor immune response. The aim of this study was to investigate and compare the immunoexpression of PD-L1, HLA-G, CD8 and GrB in the microenvironment of lip squamous cell carcinomas (LSCCs; n = 40), actinic cheilitis (ACs; n = 55), which are potentially malignant disorders of lip, and healthy lip mucosa (HLM; n = 10). The samples were submitted to immunohistochemistry for PD-L1, HLA-G, CD8 and GrB proteins. Immunostaining analysis followed a semi-quantitative method for PD-L1 and HLA-G, while CD8 and GrB expression was measured quantitatively. Protein expression was compared between the three groups of samples, as well as with the lesion`s clinicopathologic parameters and overall survival of patients with LSCC. Correlation between proteins and the type of tumor microenvironment according to a presence of PD-L1 and CD8 were also evaluated. Statistical tests included Pearson's chi-square, Fisher's exact, Mann-Whitney, Kruskal-Wallis, Spearman's correlation, as well as the log-rank for comparison of the overall survival curves of patients with LSCC built through Kaplan-Meier method. Significance was set at p < 0.05. The CD8+ and GrB+ cell numbers progressively increased from HLMs to LSCCs, with ACs exhibiting intermediate numbers (p < 0.01). Low expression of these proteins was associated with lymph node metastasis and poor tumor differentiation (p < 0.05). PD-L1 and HLA-G expression in neoplastic cells/keratinocytes and stroma/connective tissue was significantly higher in LSCCs and ACs, compared to HLMs (p < 0.05). PD-L1 was not significantly associated with clinicopathological features of the lesions. HLA-G expression by malignant cells was significantly higher in LSCCs with distant metastasis (p = 0.041). Most LSCCs showed coexistence of PD-L1⁺ and CD8⁺ cells (72.5%) in the tumor microenvironment. PD-L1 was directly correlated to CD8+ and GrB⁺ lymphocytic infiltration in LSCCs (p < 0.05). Only advanced N stage, M stage, TNM clinical stage, and poorly differentiated tumors were associated with lower overall survival of LSCCs patients (p < 0.05). Our findings suggest that the microenvironment of LSCCs is more cytotoxic than that of ACs and HLMs. However, we also observed that as PD-L1 and HLA-G immunosuppressive molecules are consistently expressed from ACs and are maintained until advanced stages of LSCCs, and that PD-L1 expression was correlated with cytotoxic activity in carcinomas, which suggests that that these proteins may appear as an escape mechanism against an active antitumor response at different stages of lip carcinogenesis.

MEMBROS DA BANCA:
Externo à Instituição - ALINE CARVALHO BATISTA - UFG
Externo à Instituição - CASSIANO FRANCISCO WEEGE NONAKA - UEPB
Presidente - 2492713 - ERICKA JANINE DANTAS DA SILVEIRA
Interno - 346077 - LELIA BATISTA DE SOUZA
Interno - 1298808 - MARCIA CRISTINA DA COSTA MIGUEL