RESUMEN
INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare, highly aggressive, and relatively chemoresistant and radioresistant malignancy with limited therapeutic options. Our objective was to investigate the prevalence of programmed death ligand 1 (PD-L1) and the characteristics of the immune environment in this disease. METHODS: A total of 99 archival tumors from advanced-stage MPM were immunohistochemically tested in parallel for PD-L1 in two different laboratories, and 87 of them were profiled for immune gene expression by NanoString analysis for 800 genes. A prior study on the same samples indicated a low mutational load with a complex mutational landscape of genetic variations more frequently associated with the p53/DNA repair and phosphoinisitide-3-kinase pathways. RESULTS: PD-L1 expression was found in 16% of the MPM tumor samples, either in the tumor cells or the infiltrating immune cells. Gene expression analysis suggested that MPM is an inflamed tumor type and can be classified into three different subgroups on the basis of the different expression profiles of immune-related genes, of which two groups showed varying degrees of expression of immune-related genes. Overall, these molecular findings suggest that these subgroups of MPM associated with PD-L1 positivity and expression of immune-related genes accounting for 60% of MPMs represent a candidate subtype that may respond to cancer immunotherapy. CONCLUSIONS: These data suggest that 60% of patients with MPM characterized by either PD-L1 expression or an inflamed status are attractive candidates for cancer immunotherapeutic options.
Asunto(s)
Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Neoplasias Pulmonares/inmunología , Mesotelioma/inmunología , Neoplasias Pleurales/inmunología , Microambiente Tumoral/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/genética , Biomarcadores de Tumor/genética , Femenino , Estudios de Seguimiento , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Masculino , Mesotelioma/genética , Mesotelioma/patología , Mesotelioma Maligno , Persona de Mediana Edad , Neoplasias Pleurales/genética , Neoplasias Pleurales/patología , Pronóstico , Tasa de SupervivenciaRESUMEN
In early stage non-small cell lung cancer (NSCLC) large randomized trials have demonstrated that in patients with radically resected disease adjuvant chemotherapy improves 5-year survival rates. However, a customization of systemic treatment is needed to avoid treatments in patients cured by surgery alone or to justify the use of adjuvant chemotherapy in high risk patients, including those in stage IA. Recently, the possibility of identifying prognostic and predictive factors related to the genetic signatures of the tumor that could affect adjuvant and neo-adjuvant treatment choices for resectable non-small cell lung cancer (NSCLC) has been of interest. This review summarizes the current status and future opportunities for clinical application of genotyping and genomic tests in early NSCLC.