RESUMO
The mechanisms triggering metastasis in pheochromocytoma/paraganglioma are unknown, hindering therapeutic options for patients with metastatic tumors (mPPGL). Herein we show by genomic profiling of a large cohort of mPPGLs that high mutational load, microsatellite instability and somatic copy-number alteration burden are associated with ATRX/TERT alterations and are suitable prognostic markers. Transcriptomic analysis defines the signaling networks involved in the acquisition of metastatic competence and establishes a gene signature related to mPPGLs, highlighting CDK1 as an additional mPPGL marker. Immunogenomics accompanied by immunohistochemistry identifies a heterogeneous ecosystem at the tumor microenvironment level, linked to the genomic subtype and tumor behavior. Specifically, we define a general immunosuppressive microenvironment in mPPGLs, the exception being PD-L1 expressing MAML3-related tumors. Our study reveals canonical markers for risk of metastasis, and suggests the usefulness of including immune parameters in clinical management for PPGL prognostication and identification of patients who might benefit from immunotherapy.
Assuntos
Neoplasias das Glândulas Suprarrenais , Segunda Neoplasia Primária , Paraganglioma , Feocromocitoma , Humanos , Neoplasias das Glândulas Suprarrenais/genética , Genômica , Paraganglioma/genética , Paraganglioma/imunologia , Feocromocitoma/genética , Feocromocitoma/imunologia , Microambiente Tumoral/genéticaRESUMO
Hydrothermal carbonization (HTC) is a facile, low-cost and eco-friendly thermal conversion process that has recently gained attention with a growing number of publications (lower 50 in 2000 to over 1500 in 2020). Despite being a promising technology, problems such as operational barriers, complex reaction mechanisms and scaling have to be solved to make it a commercial technology. To bridge this current gap, this review elaborates on the chemistry of the conversion of lignocellulosic biomass. Besides, a comprehensive overview of the influence of the HTC operational conditions (pH, temperature, water:biomass ratio, residence time and water recirculation) are discussed to better understand how hydrochar with desired properties can be efficiently produced. Large-scale examples of the application of HTC are also presented. Current applications of hydrochar in the fields of energy, biocatalysis and environment are reviewed. Finally, economic cost and future prospects are analyzed.