STUDY of the Tumor Microenvironment in Carcinoma
Oral and Oropharyngeal epidermoid and Its Implication
prognosis

Name: CAMILA BATISTA DANIEL

Publication date: 12/02/2020
Advisor:

Namesort descending Role
SANDRA LÚCIA VENTORIN VON ZEIDLER Advisor *

Examining board:

Namesort descending Role
DANIEL CLAUDIO DE OLIVEIRA GOMES Internal Examiner *
SANDRA LÚCIA VENTORIN VON ZEIDLER Advisor *

Summary: Inflammatory cells can assist important processes of carcinogenesis, such as
angiogenesis, invasion and metastasis. It has been shown that systemic inflammation,
as well as the presence of tumour-infiltrating inflammation cells, negatively affects the
clinical outcome. In this sense, the prognostic value of inflammatory markers has been
explored in several types of cancer. In this study, we investigated the potential
biomarker of the pre-treatment neutrophil-lymphocyte ratio (NLR) in peripheral blood,
PD-L1 expression in tumour and inflammatory cells and tumour-associated neutrophils
and lymphocytes in oral and oropharyngeal squamous cell carcinoma (OSCC). An
international multicenter retrospective study was conducted with biological samples,
clinical and follow-up data from 199 individuals with OSCC from Brazil and United
Kingdom. Histological slides were evaluated for invasion pattern, Tumour-infiltrating
lymphocytes (TIL) and presence of vascular, lymphatic and perineural invasion.
Paraffinized tumour tissues were subjected to immunohistochemical reaction to
identify tumour-associated neutrophils (TAN) and to evaluate PD-L1 expression. To
determine NLR, absolute neutrophil and lymphocyte counts were obtained from blood
counts performed in the period prior to treatment. TAN and NLR were dichotomized
according to the cutoff, established by means of a ROC curve. TIL was classified as
low, moderate and high and the PD-L1 expression was assessed using the Combined
Positive Score (CPS) method. Our results showed that peritumoral neutrophils were
associated with worse disease-free survival. Low TIL and increased NLR were
associated with larger tumor size and advanced disease. Increased NLR was also
associated with smoking and drinking. PD-L1 expression did not show a significant
association with the clinical-pathological characteristics and prognostic indicators
analysed. The inflamed tumor microenvironment, characterized by the high expression
of PD-L1, low TIL and high TAN, was associated with worse overall survival. Our
investigations indicate that systemic inflammation and the inflamed tumour
microenvironment can be considered as prognostic biomarkers in OSCC, however, in
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our sample group, the increase in NRL was not related to the increase in neutrophil
infiltration and the inflamed tumor microenvironment.

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