RESUMEN
The gut microbiota influences the clinical responses of cancer patients to immunecheckpoint inhibitors (ICIs). However, there is no consensus definition of detrimental dysbiosis. Based on metagenomics (MG) sequencing of 245 non-small cell lung cancer (NSCLC) patient feces, we constructed species-level co-abundance networks that were clustered into species-interacting groups (SIGs) correlating with overall survival. Thirty-seven and forty-five MG species (MGSs) were associated with resistance (SIG1) and response (SIG2) to ICIs, respectively. When combined with the quantification of Akkermansia species, this procedure allowed a person-based calculation of a topological score (TOPOSCORE) that was validated in an additional 254 NSCLC patients and in 216 genitourinary cancer patients. Finally, this TOPOSCORE was translated into a 21-bacterial probe set-based qPCR scoring that was validated in a prospective cohort of NSCLC patients as well as in colorectal and melanoma patients. This approach could represent a dynamic diagnosis tool for intestinal dysbiosis to guide personalized microbiota-centered interventions.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Microbioma Gastrointestinal , Inmunoterapia , Neoplasias Pulmonares , Neoplasias , Femenino , Humanos , Masculino , Akkermansia , Carcinoma de Pulmón de Células no Pequeñas/microbiología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Disbiosis/microbiología , Heces/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Inmunoterapia/métodos , Neoplasias Pulmonares/microbiología , Neoplasias Pulmonares/tratamiento farmacológico , Metagenómica/métodos , Neoplasias/microbiología , Resultado del TratamientoRESUMEN
Greenhouse gas (GHG) accounting in industrial plants usually has multiple purposes, including mandatory reporting, shareholder and stakeholder communication, developing key performance indicators (KPIs), or informing cost-effective mitigation options. Current carbon accounting systems, such as the one required by the European Union Emission Trading Scheme (EU ETS), ignore the system context in which emissions occur. This hampers the identification and evaluation of comprehensive mitigation strategies considering linkages between materials, energy, and emissions. Here, we propose a carbon accounting method based on multilevel material flow analysis (MFA), which aims at addressing this gap. Using a Norwegian primary aluminum production plant as an example, we analyzed the material stocks and flows within this plant for total mass flows of goods as well as substances such as aluminum and carbon. The results show that the MFA-based accounting (i) is more robust than conventional tools due to mass balance consistency and higher granularity, (ii) allows monitoring the performance of the company and defines meaningful KPIs, (iii) can be used as a basis for the EU ETS reporting and linked to internal reporting, (iv) enables the identification and evaluation of systemic solutions and resource efficiency strategies for reducing emissions, and (v) has the potential to save costs.
Asunto(s)
Aluminio , Gases de Efecto Invernadero , Carbono/análisis , Dióxido de Carbono/análisis , Gases de Efecto Invernadero/análisis , Instalaciones Industriales y de FabricaciónRESUMEN
Over the last decade, the composition of the gut microbiota has been found to correlate with the outcomes of cancer patients treated with immunotherapy. Accumulating evidence points to the various mechanisms by which intestinal bacteria act on distal tumors and how to harness this complex ecosystem to circumvent primary resistance to immune checkpoint inhibitors. Here, we review the state of the microbiota field in the context of melanoma, the recent breakthroughs in defining microbial modes of action, and how to modulate the microbiota to enhance response to cancer immunotherapy. The host-microbe interaction may be deciphered by the use of "omics" technologies, and will guide patient stratification and the development of microbiota-centered interventions. Efforts needed to advance the field and current gaps of knowledge are also discussed.