RESUMO
Disappearing nail bed (DNB) is a condition characterized by irreversible epithelialization of the nail bed following long-standing onycholysis. This phenomenon can occur in fingernails and toenails. Factors implicated in the development of DNB include trauma, manicuring, and onychotillomania and dermatologic conditions like psoriasis and dermatitis. Specifically for the toenail, contributing factors also include increasing age, history of trauma, surgery, onychomycosis, and onychogryphosis. A grading system that stages the progression of onycholysis to DNB has been proposed to aid clinicians in the diagnosis and treatment of these conditions. Several methods have been designated for the treatment of DNB.
Assuntos
Doenças da Unha , Onicólise , Onicomicose , Psoríase , Humanos , Doenças da Unha/diagnóstico , Doenças da Unha/etiologia , Doenças da Unha/terapia , Unhas/cirurgia , Onicólise/diagnóstico , Onicólise/etiologia , Onicólise/terapiaRESUMO
How tumor-infiltrating T lymphocytes (TILs) adapt to the metabolic constrains within the tumor microenvironment (TME) and to what degree this affects their ability to combat tumor progression remain poorly understood. Using mouse melanoma models, we report that CD8+ TILs enhance peroxisome proliferator-activated receptor (PPAR)-α signaling and catabolism of fatty acids (FAs) when simultaneously subjected to hypoglycemia and hypoxia. This metabolic switch partially preserves CD8+ TILs' effector functions, although co-inhibitor expression increases during tumor progression regardless of CD8+ TILs' antigen specificity. Further promoting FA catabolism improves the CD8+ TILs' ability to slow tumor progression. PD-1 blockade delays tumor growth without changing TIL metabolism or functions. It synergizes with metabolic reprogramming of T cells to achieve superior antitumor efficacy and even complete cures.