Tumor-induced senescent T cells promote the secretion of pro-inflammatory cytokines and angiogenic factors by human monocytes/macrophages through a mechanism that involves Tim-3 and CD40L

Solid tumors are infiltrated by immune cells where macrophages and senescent T cells are highly represented. Within the tumor microenvironment, a cross-talk between the infiltrating cells may occur conditioning the characteristic of the in situ immune response. Our previous work showed that tumors induce senescence of T cells, which are powerful suppressors of lympho-proliferation. In this study, we report that Tumor-Induced Senescent (TIS)-T cells may also modulate monocyte activation. To gain insight into this interaction, CD4+ or CD8+TIS-T or control-T cells were co-incubated with autologous monocytes under inflammatory conditions. After co-culture with CD4+ or CD8+TIS-T cells, CD14+ monocytes/macrophages (Mo/Ma) exhibit a higher expression of CD16+ cells and a reduced expression of CD206. These Mo/Ma produce nitric oxide and reactive oxygen species; however, TIS-T cells do not modify phagocyte capacity of Mo/Ma. TIS-T modulated-Mo/Ma show a higher production of pro-inflammatory cytokines (TNF, IL-1β and IL-6) and angiogenic factors (MMP-9, VEGF-A and IL-8) and a lower IL-10 and IP-10 secretion than monocytes co-cultured with controls. The mediator(s) present in the supernatant of TIS-T cell/monocyte-macrophage co-cultures promote(s) tubulogenesis and tumor-cell survival. Monocyte-modulation induced by TIS-T cells requires cell-to-cell contact. Although CD4+ shows different behavior from CD8+TIS-T cells, blocking mAbs against T-cell immunoglobulin and mucin protein 3 and CD40 ligand reduce pro-inflammatory cytokines and angiogenic factors production, indicating that these molecules are involved in monocyte/macrophage modulation by TIS-T cells. Our results revealed a novel role for TIS-T cells in human monocyte/macrophage modulation, which may have deleterious consequences for tumor progression. This modulation should be considered to best tailor the immunotherapy against cancer.Fil: Ramello, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Tosello Boari, Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Canale, Fernando Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Mena, Hebe Agustina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Negrotto, Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Gastman, B. Cleveland Clinic; Estados UnidosFil: Gruppi, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Acosta Rodriguez, Eva Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; ArgentinaFil: Montes, Carolina Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentin

Performance evaluation of polymer-filled metal fused filament fabrication tooling for profile extrusion

The application of additive manufacturing (AM) for tooling in the mould and die industry brings a disruptive potential in process performance, design flexibility and product enhancements. Maturing of existing AM technologies and emerging technologies such as metal-fused filament fabrication (metal FFF) can further support the applicability of AM tooling in polymer profile extrusion. This study provides a complete characterization of metal FFF 17–4 PH stainless-steel die inserts and evaluates their applicability in a polymer extrusion process chain. The presented experimental assessment pivots on the metrological characterization of the produced inserts and the impact of the insert characteristics on the final extrudates’ product. Considering a conventionally manufactured benchmark insert, produced via subtractive methods (CNC machining and electrical discharge machining), comparable results for AM tools in terms of extrudates’ quality and process repeatability are presented. It was found that despite significant higher average surface parameters for AM insert tools (Sa = 2–9 μm vs. Sa = 0.3–0.9 μm for dies manufactured by machining), a much smaller difference was observed in the resulting quality of polymer extrudates’ product. The roughness generation effect of polymer profile extrusion based on the different dies’ internal surface roughness topography and the effect on extrudates product was evaluated. Three-dimensional average roughness Sa on acrylonitrile butadiene styrene extrudate surfaces obtained from conventionally machined dies was in the range of 0.3 μm. For extrudates obtained from additively manufactured dies, their Sa was in the rage of 0.5 μm (despite the much higher surface roughness of FFF dies compared to machined dies). The results confirm that with suitable extrudates’ product requirement, it is feasible to apply metal FFF as the selected manufacturing method for tooling in polymer profile extrusion

A study of irrigation and restorations of old coffe trees. I. Results from Botucatu experiment station

No presente trabalho, são relatados os resultados de seis anos de um estudo, feito sob a forma de ensaio de campo, com a finalidade de verificar a possibilidade prática da restauração da lavoura velha de café, no Estado de São Paulo com o emprego da irrigação associada a outras práticas agrícolas. Foram estudados os efeitos da irrigação em três épocas de aplicação e os efeitos das combinações fatorais de NPK (ditas dosagens), presença e ausência de esterco de curral e presença e ausência de adubação verde intercalar, utilizando o delineamento de blocos balanceados e canteiros, subdivididos, com um total de nove blocos, cada um com oito tratamentos de dez plantas, totalizando 2674 cafeeiros, inclusive as bordaduras, abrangendo a área total aproximada de 38000 metros quadrados. Foi instalado num dos melhores talhões de cafezal velho da variedade "Bourbon Vermelho", plantado há cerca de 40 anos, em terra do tipo roxa misturada, desbravada de mata virgem, na atual Estação Experimental de Botucatu, antiga Fazenda do Lageado de propriedade do Ministério da Agricultura. A produção média dos talhões nos últimos nove anos que precederam a instalação do ensaio foi de 43,2 arrobas de café beneficiado por mil pés ou cerca de 463 kg/ha. O estudo sequencial das produções médias quadrienais progressivas revela que a produção do talhão declina lentamente.This paper reports and discusses results referring to a field trial set up to study the possibilities of restoring the productivity of an old coffee plantation through irrigation and fertilization. The six year study which started in 1955, was conducted in a representative, well kept coffee grove of Bourbon variety, about 40 years old, located at the Experiment Station of Botucatu, State of São Paulo. Nine randomized blocks were used with a 2x2x2 factorial for the treatments within each block. The following treatments were compared; complete chemical fertilizer in two dosages, with and without manure, and with and without green manure as an annual intercrop. The irrigation treatment included, irrigation starting in April, starting in July, and no irrigation application was determined by soil moisture depletion, when about 70 mm were consumed from the 0-80 cm soil layer. The results showed substantial increase in production during the dry years, however the significance of this production was diminished by the biennial beating effect occurring in coffee plants. During wet years, that is, when the normal rainy period is lengthened due to unexpected early rains (after irrigation has already been carried out) production may often be reduced due to excessive leaching of needed fertilizer. Use of green manure as an annual intercrop was shown not to increase production; the same occurring with the use of organic manure in the dosage of about 20 kg every year per coffee tree (which in actuality is a group of tree to five trees originally planted in the same hole). When production of the treated plots was compared with the untreated border plot trees, an increase of about 14% was shown due to the effect of chemical fertilizer alone. However the present economical situation in Brazil does not favor the use of fertilizer on a profitable basis. Considering the success obtained in forming a new coffee plantation in places where there was before an old one, a practice which is growing in importance, it would riot be advisable to recommend the expenditure of trying to improve an old coffee plantation of the type reported