Expression of immunoregulatory molecules in oral squamous cell carcinoma microenvironment

  1. Peña Cardelles, Juan Francisco
Dirigida por:
  1. José Juan Pozo Kreilinger Director
  2. José Luis Cebrián Carretero Codirector/a
  3. José Ernesto Moro Rodríguez Codirector/a
  4. Custodia García Jiménez Codirector/a

Universidad de defensa: Universidad Rey Juan Carlos

Fecha de defensa: 23 de julio de 2021

Tribunal:
  1. G. Esparza Gómez Presidente
  2. Rafael Gómez de Diego Secretario/a
  3. Lorenzo Arriba de la Fuente Vocal

Tipo: Tesis

Teseo: 675795 DIALNET lock_openTESEO editor

Resumen

Introduction Oral squamous cell carcinoma (OSCC) is the most frequent neoplasm among head and neck carcinomas, this group is one of the most frequent groups of cancers globally. The morbidity of its treatment is very high, as is mortality, and the survival of patients with this disease at five years is approximately 60%. Unfortunately, the average survival of patients with recurrence of the disease or metastasis is approximately 8-10 months. The histopathological characteristics of OSCC have been studied, and a histologic risk assessment system has been developed, motivated by the high rate of relapses of this neoplasia. Despite that there are studies on the microenvironment in head and neck cancer, the tumour microenvironment that exists around OSCCs has not yet been studied in depth, which would improve the understanding of this tumour in the face of the emergence of immunotherapy since clinical trials conducted in recent years have evaluated drugs whose therapeutic targets are various immunological checkpoints. Objectives To know the relationship of the immune-checkpoint PD-1 / PD-L1 with the clinical evolution of OSCC; to assess survival in OSCC based on the characteristics of TME and histologic risk score; and to evaluate the clinical and histopathological relationship of OSCC with immunological TME. Methods A retrospective study was carried out on 65 samples from patients with OSCC on the floor of the mouth or tongue. Clinicopathological variables and the expression of the biomarkers PD-1, PD-L1, FoxP3, CD4, CD8, CSF1R, and p16 were recorded. The relationship of the clinical and histological variables with the expression of the biomarkers was evaluated, and survival was studied. Results The univariate and multivariate analysis indicated that positive PD-1 expression was an independent protective factor for survival (overall, disease-free, disease-specific survival) and that high PD-L1 also improved survival. Poorly differentiated histological grade and metastasis were associated with a worse prognosis. Conclusion PD-1 is a protective survival factor that is maintained independently of PD-L1 expression. High values of PD-L1 expression also improve survival, while low values are associated with a worse prognosis. Higher expression of PD-1 is observed in smaller tumours, and higher expression of PD-L1 is more likely in women. No relationship between the tumour microenvironment and histologic risk score was found to influence the survival patterns studied in the OSCC. There is no evidence of a relationship between the histopathological features and the studied markers, although the positive PD-1 and PD-L1 cases have a lower risk of a high WPOI score, and positive PD-1 expression was associated with a lower DOI.