Ecto-5'-Nucleotidase (CD73) Regulates the Survival of CD8+ T Cells.

Ecto-5'-nucleotidase (CD73) is an enzyme present on the surface of tumor cells whose primary described function is the production of extracellular adenosine. Due to the immunosuppressive properties of adenosine, CD73 is being investigated as a target for new antitumor therapies. We and others have described that CD73 is present at the surface of different CD8+ T cell subsets. Nonetheless, there is limited information as to whether CD73 affects CD8+ T cell proliferation and survival. In this study, we assessed the impact of CD73 deficiency on CD8+ T cells by analyzing their proliferation and survival in antigenic and homeostatic conditions. Results obtained from adoptive transfer experiments demonstrate a paradoxical role of CD73. On one side, it favors the expression of interleukin-7 receptor α chain on CD8+ T cells and their homeostatic survival; on the other side, it reduces the survival of activated CD8+ T cells under antigenic stimulation. Also, upon in vitro antigenic stimulation, CD73 decreases the expression of interleukin-2 receptor α chain and the anti-apoptotic molecule Bcl-2, findings that may explain the reduced CD8+ T cell survival observed in this condition. These results indicate that CD73 has a dual effect on CD8+ T cells depending on whether they are subject to an antigenic or homeostatic stimulus, and thus, special attention should be given to these aspects when considering CD73 blockade in the design of novel antitumor therapies.

P2X7 Receptor at the Crossroads of T Cell Fate.

The P2X7 receptor is a ligand-gated, cation-selective channel whose main physiological ligand is ATP. P2X7 receptor activation may also be triggered by ARTC2.2-dependent ADP ribosylation in the presence of extracellular NAD. Upon activation, this receptor induces several responses, including the influx of calcium and sodium ions, phosphatidylserine externalization, the formation of a non-selective membrane pore, and ultimately cell death. P2X7 receptor activation depends on the availability of extracellular nucleotides, whose concentrations are regulated by the action of extracellular nucleotidases such as CD39 and CD38. The P2X7 receptor has been extensively studied in the context of the immune response, and it has been reported to be involved in inflammasome activation, cytokine production, and the migration of different innate immune cells in response to ATP. In adaptive immune responses, the P2X7 receptor has been linked to T cell activation, differentiation, and apoptosis induction. In this review, we will discuss the evidence of the role of the P2X7 receptor on T cell differentiation and in the control of T cell responses in inflammatory conditions.

Tissue-resident memory CD8+ T cells amplify anti-tumor immunity by triggering antigen spreading through dendritic cells.

Tissue-resident memory CD8+ T (Trm) cells mediate potent local innate and adaptive immune responses and play a central role against solid tumors. However, whether Trm cells cross-talk with dendritic cells (DCs) to support anti-tumor immunity remains unclear. Here we show that antigen-specific activation of skin Trm cells leads to maturation and migration to draining lymph nodes of cross-presenting dermal DCs. Tumor rejection mediated by Trm cells triggers the spread of cytotoxic CD8+ T cell responses against tumor-derived neo- and self-antigens via dermal DCs. These responses suppress the growth of intradermal tumors and disseminated melanoma lacking the Trm cell-targeted epitope. Moreover, analysis of RNA sequencing data from human melanoma tumors reveals that enrichment of a Trm cell gene signature associates with DC activation and improved survival. This work unveils the ability of Trm cells to amplify the breath of cytotoxic CD8+ T cell responses through DCs, thereby strengthening anti-tumor immunity.

Optimización del proceso de tratamiento de aguas residuales de una industria cervecera

Se estudió la optimización del sistema de tratamiento de aguas residuales de una industria cervecera que funciona bajo la modalidad de sistema combinado de reactor anaerobio y lodos activados. La evaluación comprendió dos etapas. Durante la primera, con duración de seis meses, se analizó el funcionamiento de la planta con las características y parámetros operacionales prevalecientes de desvío hacia el tratamiento aeróbico mayor a 50%, uso de dos tanques de aireación y elevada producción de lodo. La segunda etapa abarcó cuatro meses en los cuales el sistema trabajó con el modelo operacional propuesto con la finalidad de mejorar el tratamiento: disminución de la tasa de desvío hasta 30% y utilización de un solo tanque de aireación. En cada etapa se realizaron mediciones de SST, SSV y DQO a la entrada y salida del reactor anaerobio y de los tanques de aireación. Los resultados se compararon con las especificaciones de diseño correspondientes y se aplicaron las condiciones necesarias para disminuir la tasa de desvío hacia el proceso aeróbico mediante monitoreo del volumen y concentración del afluente, aplicando cambios estratégicos en los parámetros del reactor que incrementasen su eficiencia. Se obtuvo una reducción del desvío de 53 a 34%, disminuyendo el lodo de descarte generado en el sistema aeróbico de 3670mg SST/l con dos tanques de aireación hasta 2947mg SST/l empleando un tanque, manteniendo los mismos valores de relación SSV:SST (0,55) y una eficiencia de remoción global en términos de DQO de 98%.

OPTIMIZATION OF THE TREATMENT PROCESS FOR RESIDUAL WATER FROM A BEER INDUSTRY.

The optimization of the treatment process for residual waters from a brewery operating under the modality of an anaerobic reactor and activated sludge combination was studied in two phases. In the first stage, lasting for six months, the characteristics and parameters of the plant operation were analyzed, wherein a diversion rate of more than 50% to aerobic treatment, the use of two aeration tanks and a high sludge production prevailed. The second stage comprised four months during which the system worked under the proposed operational model, with the aim of improving the treatment: reduction of the diversion rate to 30% and use of only one aeration tank. At each stage, TSS, VSS and COD were measured at the entrance and exit of the anaerobic reactor and the aeration tanks. The results were compared with the corresponding design specifications and the needed conditions were applied to reduce the diversion rate towards the aerobic process through monitoring the volume and concentration of the affluent, while applying the strategic changes in reactor parameters needed to increase its efficiency. A diversion reduction from 53 to 34% was achieved, reducing the sludge discharge generated in the aerobic system from 3670mg TSS/l with two aeration tanks down to 2947mf TSS/l using one tank, keeping the same relation VSS:TSS (0.55) and an efficiency of total removal of 98% in terms of COD.

Estudou-se a otimização do sistema de tratamento de águas residuais de uma indústria cervejeira que funciona sob a modalidad de sistema combinado de reactor anaeróbio e lodos ativados. A avaliação abrangeu duas etapas. Durante a primeira, com duração de seis meses, se analisou o funcionamento da fábrica com as características e parâmetros operacionais prevalecentes de desvio para o tratamento aeróbico maior a 50%, uso de dois tanques de aireação e elevada produção de lodo. A segunda etapa abrangeu quatro meses nos quais o sistema trabalhou com o modelo operacional proposto com a finalidade de melhorar o tratamento: diminuição da taxa de desvio até 30% e utilização de um só tanque de aireação. Em cada etapa se realizaram medições de SST, SSV e DQO à entrada e saída do reactor anaeróbio e dos tanques de aireação. Os resultados se compararam com as especificações de desenho correspondentes e se aplicaram as condições necessárias para diminuir a taxa de desvio para o processo aeróbico mediante acompanhamento do volume e concentração do afluente, aplicando mudanças estratégicas nos parâmetros do reactor que incrementasem sua eficiência. Obteve-se uma redução do desvio de 53 a 34%, diminuindo o lodo de descarte gerado no sistema aeróbico de 3670mg SST/l com dois tanques de aireação até 2947mg SST/l empregando um tanque, mantendo os mesmos valores de relação SSV:SST (0,55) e uma eficiência de remoção global em termos de DQO de 98%.