RESUMO
Immunotherapy has become a new paradigm in oncology, improving outcomes for several types of cancer. However, there are some aspects about its management that remain uncertain. One of the key points that needs better understanding is the interaction between immunotherapy and gut microbiome and how modulation of the microbiome might modify the efficacy of immunotherapy. Consequently, the negative impact of systemic antibiotics and corticosteroids on the efficacy of immunotherapy needs to be clarified.
Assuntos
Corticosteroides/farmacologia , Antibacterianos/farmacologia , Interações entre Hospedeiro e Microrganismos , Inibidores de Checkpoint Imunológico/uso terapêutico , Microbiota , Neoplasias/tratamento farmacológico , Probióticos , Corticosteroides/uso terapêutico , Animais , Antibacterianos/uso terapêutico , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Inibidores de Checkpoint Imunológico/farmacologia , Imunomodulação/efeitos dos fármacos , Interações Microbianas/efeitos dos fármacos , Interações Microbianas/imunologia , Microbiota/efeitos dos fármacos , Neoplasias/etiologia , Resultado do TratamentoRESUMO
The photothermal response of plasmonic nanomaterials can be exploited for a number of biomedical applications in diagnostics (biosensing and optoacoustic imaging) and therapy (drug delivery and photothermal therapy). The most common cellular response to photothermal cancer treatment (ablation of solid tumors) using plasmonic nanomaterials is necrosis, a process that releases intracellular constituents into the extracellular milieu producing detrimental inflammatory responses. Here we report the use of laser-induced photothermal therapy employing gold nanoprisms (NPRs) to specifically induce apoptosis in mouse embryonic fibroblast cells transformed with the SV40 virus. Laser-irradiated "hot" NPRs activate the intrinsic/mitochondrial pathway of apoptosis (programmed cell death), which is mediated by the nuclear-encoded proteins Bak and Bax through the activation of the BH3-only protein Bid. We confirm that an apoptosis mechanism is responsible by showing how the NPR-mediated cell death is dependent on the presence of caspase-9 and caspase-3 proteins. The ability to selectively induce apoptotic cell death and to understand the subsequent mechanisms provides the foundations to predict and optimize NP-based photothermal therapy to treat cancer patients suffering from chemo- and radioresistance.