doctoralThesis
Resposta imune e mecanismos de evasão na carcinogênese de lábio: um estudo imunoistoquímico
Fecha
2018-01-30Registro en:
LOPES, Maria Luiza Diniz de Sousa. Resposta imune e mecanismos de evasão na carcinogênese de lábio: um estudo imunoistoquímico. 2018. 94f. Tese (Doutorado em Patologia Oral) - Centro de Ciências da Saúde, Universidade Federal do Rio Grande do Norte, Natal, 2018.
Autor
Lopes, Maria Luiza Diniz de Sousa
Resumen
Immune surveillance, mainly mediated by CD8 + T lymphocytes, 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 granzyme B (GrB) in the microenvironment of lip squamous cell carcinomas (LSCCs; n =
40), actinic cheilitis (ACs; n = 55), and healthy lip mucosa (HLM; n = 10). The samples were
submitted to immunohistochemistry and the analysis followed a semi-quantitative (PD-L1 and
HLA-G) and quantitative methods (CD8 and GrB). 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 Fisher's exact, Mann-Whitney, Kruskal-Wallis, Spearman's correlation, as well
as the log-rank for comparison of the overall survival 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). Lower 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 aspects of the lesions. Most LSCCs
showed coexistence of PD-L1+ and CD8+ cells (72.5%) in the tumor microenvironment. PDL1
was directly correlated to CD8+ and GrB+ lymphocytic infiltration in LSCCs (p < 0.05).
Proteins expression was not associated with overall survival of LSCCs patients (p > 0.05). Our
findings suggest that immunosuppressive molecules PD-L1 and HLA-G are consistently
expressed from ACs and are maintained until advanced stages of LSCCs. The correlation
between PD-L1 expression and the expression of CD8 and GrB in carcinomas suggests that that
PD-L1 may appear as an escape mechanism against an active antitumor response.