Αρχειοθήκη ιστολογίου

Κυριακή 30 Σεπτεμβρίου 2018

Immune response and evasion mechanisms in lip carcinogenesis: an immunohistochemical study

Publication date: Available online 29 September 2018

Source: Archives of Oral Biology

Author(s): Maria Luiza Diniz de Sousa Lopes, Amanda Katarinny Goes Gonzaga, Carla Mosconi, Gustavo Martelli Palomino, Elismauro Francisco Mendonça, Aline Carvalho Batista, Éricka Janine Dantas da Silveira

Abstract
Objectives

Programmed death ligand-1 (PD-L1) and human leukocyte antigen-G (HLA-G) are considered immune checkpoint molecules that inhibit T-cell effectiveness, contributing to tumor immune escape. This study investigated PD-L1, HLA-G, CD8, and granzyme B (GrB) expression at different stages of lip carcinogenesis.

Design and results

Forty cases of lip squamous cell carcinoma (LSCC), 55 actinic cheilitis (AC), and 10 healthy lip mucosa (HLM) were submitted to immunohistochemistry. Semiquantitative (PD-L1, HLA-G), and quantitative (CD8, GrB) analysis were performed. PD-L1 and HLA-G expression in neoplastic cells/keratinocytes and stroma/connective tissue was significantly higher in LSCC and AC, compared to HLM (p<0.05). PD-L1 was not associated with clinicopathological features of the lesions. HLA-G expression by malignant cells was significantly higher in LSCCs with distant metastasis (p = 0.041).CD8+ and GrB+ cell numbers progressively increased from HLMs to LSCC, with AC exhibiting intermediate numbers (p<0.01). Most LSCCs showed coexistence of PD-L1+ and CD8+ cells (72.5%). PD-L1 was directly correlated to CD8+ and GrB+ lymphocytic infiltration in LSCCs (p<0.05). Low cytotoxic immune response was associated with lymph node metastasis in LSCC (p<0.05).

Conclusions

PD-L1 and HLA-G-mediated immune evasion mechanisms are likely to occur from early pre-malignant to advanced malignant stages of lip carcinogenesis, which might provide a rationale for therapeutic blockade of these pathways. PD-L1 expression in LSCCs was correlated with the cytotoxic markers, suggesting that that PD-L1 may appear as an escape mechanism in response to an active antitumor response.



https://ift.tt/2y4TSOe

Δεν υπάρχουν σχόλια:

Δημοσίευση σχολίου