Qualité physico-chimique et contamination métallique des eaux de l’Oued Hassar : impacts des eaux usées de la localité de Mediouna (Périurbain de Casablanca, Maroc)

Une des préoccupations majeures du début du XXIe siècle est la pérennité d’une ressource en eau suffisante pour satisfaire les besoins d’une  population en forte croissance dans un contexte mondial marqué par lechangement climatique et ses conséquences hydrologiques. Cette  problématique ne se limite pas à la quantité des ressources en eau, mais porte également sur leur qualité qu’il faut aujourd’hui plus que jamais bien gérer. Les activités industrielles, agricoles ou urbaines peuvent modifier la qualité des eaux et les rendre impropres à l’utilisation. C’est le cas de la zone périurbaine du Nord Est du grand Casablanca (Province de Mediouna), où le cours d’eau d’Oued Hassar reçoit, à ciel ouvert, les rejets d’eaux usées de Mediouna dont les impacts écologiques et sanitaires sont multiples. Les résultats des analyses physico-chimiques montrent que les eaux de ce cours d’eau sont caractérisées par une minéralisation  importante comme l’indiquent les valeurs élevées de la conductivité  électrique et des chlorures. De même, ces eaux présentent une pollution importante confirmée par les valeurs élevées de la DCO, le phosphore total et l’azote ammoniacal. En ce qui concerne les métaux lourds (Cd, Pb, Cr, Cu, Fe et Zn), l’analyse des résultats montre que les concentrations en éléments traces dans les eaux usées de Mediouna et de celles d’oued Hassar ne constituent pas un facteur limitant pour la réutilisation de ces eaux dans l’irrigation.Mots-clés : Casablanca, Oued Hassar, eaux usées, pollution, physicochimie, métaux lourds

Low Avidity T Cells Do Not Hinder High Avidity T Cell Responses Against Melanoma

The efficacy of T cells depends on their functional avidity, i. e., the strength of T cell interaction with cells presenting cognate antigen. The overall T cell response is composed of multiple T cell clonotypes, involving different T cell receptors and variable levels of functional avidity. Recently, it has been proposed that the presence of low avidity tumor antigen-specific CD8 T cells hinder their high avidity counterparts to protect from tumor growth. Here we analyzed human cytotoxic CD8 T cells specific for the melanoma antigen Melan-A/MART-1. We found that the presence of low avidity T cells did not result in reduced cytotoxicity of tumor cells, nor reduced cytokine production, by high avidity T cells. In vivo in NSG-HLA-A2 mice, the anti-tumor effect of high avidity T cells was similar in presence or absence of low avidity T cells. These data indicate that low avidity T cells are not hindering anti-tumor T cell responses, a finding that is reassuring because low avidity T cells are an integrated part of natural T cell responses

Mutually exclusive lymphangiogenesis or perineural infiltration in human skin squamous-cell carcinoma.

Although tumor-associated lymphangiogenesis correlates with metastasis and poor prognosis in several cancers, it also supports T cell infiltration into the tumor and predicts favorable outcome to immunotherapy. The role of lymphatic vessels in skin squamous-cell carcinoma (sSCC), the second most common form of skin cancer, remains mostly unknown. Although anti-PD-1 therapy is beneficial for some patients with advanced sSCC, a greater understanding of disease mechanisms is still needed to develop better therapies. Using quantitative multiplex immunohistochemistry, we analyzed sSCC sections from 36 patients. CD8+ T cell infiltration showed great differences between patients, whereby these cells were mainly excluded from the tumor mass. Similar to our data in melanoma, sSCC with high density of lymphatic endothelial cells showed increased CD8+ T cell density in tumor areas. An entirely new observation is that sSCC with perineural infiltration but without metastasis was characterized by low lymphatic endothelial cell density. Since both, metastasis and perineural infiltration are known to affect tumor progression and patients' prognosis, it is important to identify the molecular drivers, opening future options for therapeutic targeting. Our data suggest that the mechanisms underlying perineural infiltration may be linked with the biology of lymphatic vessels and thus stroma

Qualité bactériologique et physique des eaux de l’Oued Hassar (Casablanca, Maroc): Caractérisation et analyse en Composantes principales

The objective of this study is to evaluate the bacteriological quality of water of Oued Hassar in relation to the wastewater of Mediouna’s location and also to apply a statistical analysis using the Principal Component Analysis (PCA) to correlate data of spatio-temporal variability of bacterial indicators with those of physical parameters (temperature, pH, electrical conductivity and turbidity). The average values obtained ​​indicate that the water of this river contains a lot of amount of bacteria that indicates a faecal contamination. These values, for total coliforms, faecal coliforms and faecal Streptococci were hight and more than seven log10. Then the bacteriological quality of water of oued Hassar is classified in poor to very poor category. The Principal Component Analysis revealed that the indicator bacteria of faecal contamination presents negative correlations with the pH and the electrical conductivity, and positive correlations that are highly significant with turbidity.La présente étude consiste à évaluer la qualité bactériologique des eaux d’Oued Hassar en relation avec les effluents de la localité de Mediouna et d’appliquer une méthode statistique d’Analyse en Composantes Principales (ACP) pour corréler les données de la variabilité spatio-temporelle des indicateurs bactériologiques à ceux des paramètres physiques (température, pH, conductivité électrique et turbidité). Les valeurs moyennes obtenues révèlent que les eaux de ce cours d’eau présentent une charge très importante en bactéries indicatrices de la contamination d’origine fécale. Les teneurs en coliformes totaux, coliformes fécaux et streptocoques fécaux atteignent des valeurs importantes supérieures à sept log10. De ce fait, la qualité bactériologique des eaux d’Oued Hassar est classée dans la catégorie mauvaise à très mauvaise. L’ACP a révélé que les bactéries indicatrices de la contamination fécale présentent des corrélations négatives avec le pH et la conductivité électrique et des corrélations positives et fortement significatives avec la turbidité

Inflammatory B cells correlate with failure to checkpoint blockade in melanoma patients.

The understanding of the role of B cells in patients with solid tumors remains insufficient. We found that circulating B cells produced TNFα and/or IL-6, associated with unresponsiveness and poor overall survival of melanoma patients treated with anti-CTLA4 antibody. Transcriptome analysis of B cells from melanoma metastases showed enriched expression of inflammatory response genes. Publicly available single B cell data from the tumor microenvironment revealed a negative correlation between TNFα expression and response to immune checkpoint blockade. These findings suggest that B cells contribute to tumor growth via the production of inflammatory cytokines. Possibly, these B cells are different from tertiary lymphoid structure-associated B cells, which have been described to correlate with favorable clinical outcome of cancer patients. Further studies are required to identify and characterize B cell subsets and their functions promoting or counteracting tumor growth, with the aim to identify biomarkers and novel treatment targets

Circulating CD56^bright NK cells inversely correlate with survival of melanoma patients.

The roles of NK cells in human melanoma remain only partially understood. We characterized NK cells from peripheral blood ex vivo by flow cytometry obtained from late stage (III/IV) melanoma patients. Interestingly, we found that the abundance of CD56 <sup>bright</sup> NK cells negatively correlate with overall patient survival, together with distant metastases, in a multivariate cox regression analysis. The patients' CD56 <sup>bright</sup> NK cells showed upregulation of CD11a, CD38 and CD95 as compared to healthy controls, pointing to an activated phenotype as well as a possible immune regulatory role in melanoma patients. After stimulation in vitro, CD56 <sup>bright</sup> NK cells produced less TNFα and GMCSF in patients than controls. Furthermore, IFNγ production by the CD56 <sup>bright</sup> NK cells correlated inversely with overall survival. Our results highlight that abundance and function of CD56 <sup>bright</sup> NK cells are associated with melanoma patient survival, emphasizing the potential of NK cell subsets for biomarker discovery and future therapeutic targeting

Lymphatic vessel density is associated with CD8⁺ T cell infiltration and immunosuppressive factors in human melanoma.

Increased density of tumor-associated lymphatic vessels correlates with poor patient survival in melanoma and other cancers, yet lymphatic drainage is essential for initiating an immune response. Here we asked whether and how lymphatic vessel density (LVD) correlates with immune cell infiltration in primary tumors and lymph nodes (LNs) from patients with cutaneous melanoma. Using immunohistochemistry and quantitative image analysis, we found significant positive correlations between LVD and CD8 <sup>+</sup> T cell infiltration as well as expression of the immunosuppressive molecules inducible nitric oxide synthase (iNOS) and 2,3-dioxygénase (IDO). Interestingly, similar associations were seen in tumor-free LNs adjacent to metastatic ones, indicating loco-regional effects of tumors. Our data suggest that lymphatic vessels play multiple roles at tumor sites and LNs, promoting both T cell infiltration and adaptive immunosuppressive mechanisms. Lymph vessel associated T cell infiltration may increase immunotherapy success rates provided that the treatment overcomes adaptive immune resistance

Developmental and pathological lymphangiogenesis: from models to human disease.

The lymphatic vascular system, the body's second vascular system present in vertebrates, has emerged in recent years as a crucial player in normal and pathological processes. It participates in the maintenance of normal tissue fluid balance, the immune functions of cellular and antigen trafficking and absorption of fatty acids and lipid-soluble vitamins in the gut. Recent scientific discoveries have highlighted the role of lymphatic system in a number of pathologic conditions, including lymphedema, inflammatory diseases, and tumor metastasis. Development of genetically modified animal models, identification of lymphatic endothelial specific markers and regulators coupled with technological advances such as high-resolution imaging and genome-wide approaches have been instrumental in understanding the major steps controlling growth and remodeling of lymphatic vessels. This review highlights the recent insights and developments in the field of lymphatic vascular biology