Internalisation des valeurs de la finance durable : les déterminants organisationnels

Ce mémoire contribue au champ de la finance durable et répond à la question de recherche « quels sont les facteurs déterminants organisationnels qui contribuent à l'internalisation des valeurs de la finance durable dans les pratiques de gestion ? ». Il est composé de deux articles. Le premier article examine les fondations de la finance durable définie comme l'intégration par les entreprises œuvrant dans le secteur financier, des préoccupations d'ordre environnemental, social et de gouvernance (ESG) dans leur prise de décision et leurs activités organisationnelles. Car, les investisseurs et les agences de notation considèrent de plus en plus les facteurs ESG comme des déterminants de la viabilité à long terme des entreprises du secteur financier. La revue de littérature montre que, en réponse à cette attente des parties prenantes, ces entreprises font face à l'obligation d'internaliser les facteurs non financiers ESG dans leurs processus de gestion responsable et de création de valeurs durables. Le deuxième article répond à la question de savoir « comment les compagnies d'assurance internalisent-elles les valeurs de la finance durable dans leurs pratiques de gestion ? ». Après avoir réalisé des entrevues auprès d'assureurs européens, il est possible de constater que la perception en matière de développement durable, qui est souvent large et complexe, vient influencer le degré d'internalisation de ces valeurs dans les pratiques de gestion. L'analyse des résultats permet d'observer que les entreprises déterminent d'abord leur intention, par l'engagement de la direction, leur motivation et leur structure de gouvernance. Ensuite, celles-ci déploient une approche basée sur une combinaison de mécanismes formels et informels. Plus précisément, la culture organisationnelle, le leadership et les pratiques de gestion soutiennent la durabilité, autant que les politiques, les processus et les indicateurs de performance ESG. Finalement, un modèle intégré a pu être proposé à la suite de cette étude qui s'avère utile pour les gestionnaires d'assureurs qui désirent s'approprier les valeurs de la finance durable ou améliorer leurs pratiques de gestion en ce sens.This dissertation contributes to the field of sustainable finance and answers the research question "what are the organizational determinants that contribute to the internalization of sustainable finance values in management practices? It is composed of two articles. The first article examines the foundations of sustainable finance, defined as the integration of environmental, social and governance (ESG) concerns into the decision-making and organizational activities of companies operating in the financial sector. This is because investors and rating agencies are increasingly considering ESG factors as determinants of the long-term viability of companies in the financial sector. The literature review shows that, in response to this stakeholder expectation, these companies are faced with the obligation to internalize non-financial ESG factors in their responsible management and sustainable value creation processes. The second article answers the question "how do insurance companies internalize the values of sustainable finance in their management practices? After conducting interviews with European insurers, it is possible to observe that the perception of sustainable development, which is often broad and complex, influences the degree of internalization of these values in the management. The analysis of the results shows that companies first determine their intention through management commitment, motivation and governance structure. Then, they deploy an approach based on a combination of formal and informal mechanisms. Specifically, organizational culture, leadership and management practices support sustainability, as do policies, processes and ESG performance indicators. Finally, an integrated model was proposed as a result of this study, which is useful for insurer managers who wish to appropriate the values of sustainable finance or improve their management practices in this sense

Toward harmonized phenotyping of human myeloid-derived suppressor cells by flow cytometry: results from an interim study

There is an increasing interest for monitoring circulating myeloid-derived suppressor cells (MDSCs) in cancer patients, but there are also divergences in their phenotypic definition. To overcome this obstacle, the Cancer Immunoguiding Program under the umbrella of the Association of Cancer Immunotherapy is coordinating a proficiency panel program that aims at harmonizing MDSC phenotyping. After a consultation period, a two-stage approach was designed to harmonize MDSC phenotype. In the first step, an international consortium of 23 laboratories immunophenotyped 10 putative MDSC subsets on pretested, peripheral blood mononuclear cells of healthy donors to assess the level of concordance and define robust marker combinations for the identification of circulating MDSCs. At this stage, no mandatory requirements to standardize reagents or protocols were introduced. Data analysis revealed a small intra-laboratory, but very high inter-laboratory variance for all MDSC subsets, especially for the granulocytic subsets. In particular, the use of a dead-cell marker altered significantly the reported percentage of granulocytic MDSCs, confirming that these cells are especially sensitive to cryopreservation and/or thawing. Importantly, the gating strategy was heterogeneous and associated with high inter-center variance. Overall, our results document the high variability in MDSC phenotyping in the multicenter setting if no harmonization/standardization measures are applied. Although the observed variability depended on a number of identified parameters, the main parameter associated with variation was the gating strategy. Based on these findings, we propose further efforts to harmonize marker combinations and gating parameters to identify strategies for a robust enumeration of MDSC subsets

Longitudinal evolution of the immune suppressive glioma microenvironment in different synchronous lesions during treatment

The role of immune suppression in glioma progression has been clearly established.1 We and others have recently demonstrated that myeloid cells play a major role in the tumor microenvironment of glioblastoma (GBM) patients,2,3 and that not only bone marrow-derived macrophages (BMDMs) have a higher intrinsic immune suppressive ability compared to resident microglial cells (MG), but also that this ability greatly increases going from the periphery to the tumor core.3 In lower grade gliomas (grades II and III), a much lower amount of BMDM is present, devoid of immune suppressive ability.3 We present here a longitudinal analysis of the immune infiltrate in a patient with a synchronous occurrence of GBM in the left temporal lobe, and a low-grade glioma (LGG) in the right frontal lobe, with discordant isocitrate dehydrogenase (IDH)-mutational status,4 followed by two GBM relapse

Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards

Myeloid-derived suppressor cells (MDSCs) have emerged as major regulators of immune responses in cancer and other pathological conditions. In recent years, ample evidence supports key contributions of MDSC to tumour progression through both immune-mediated mechanisms and those not directly associated with immune suppression. MDSC are the subject of intensive research with >500 papers published in 2015 alone. However, the phenotypic, morphological and functional heterogeneity of these cells generates confusion in investigation and analysis of their roles in inflammatory responses. The purpose of this communication is to suggest characterization standards in the burgeoning field of MDSC research

Human MDSCs derived from the bone marrow maintain their functional ability but have a reduced frequency of induction in the elderly compared to pediatric donors

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immunosuppressive cells developing from myeloid progenitors, which are enriched in pathological conditions such as cancer, and are known to inhibit the functions of effector T cells. During aging, several changes occur both at the adaptive and innate immune system level, in a process defined as immunoscenescence. In particular, the low-grade inflammation state observed in the elderly appears to affect hematopoiesis. We previously demonstrated that the combination of GM-CSF and G-CSF drives the in vitro generation of bone marrow-derived MDSCs (BM-MDSCs) from precursors present in human bone marrow aspirates of healthy donors, and that these cells are endowed with a strong immune suppressive ability, resembling that of cancer-associated MDSCs. In the present work we investigated BM-MDSCs induction and functional ability in a cohort of pediatric versus elderly donors. To this aim, we analyzed the differences in maturation stages and ability to suppress T cell proliferation. We found that the ex vivo distribution of myeloid progenitors is similar between pediatric and elderly individuals, whereas after cytokine treatment a significant reduction in the more immature compartment is observed in the elderly. Despite the decreased frequency, BM-MDSCs maintain their suppressive capacity in aged donors. Taken together, these results indicate that in vitro induction of MDSCs from the BM is reduced with aging and opens new hypotheses on the role of age-related processes in myelopoiesis

Effect of a nitric oxide donor on maternal hemodynamics in fetal growth restriction

OBJECTIVE: To evaluate maternal cardiovascular effects of nitric oxide (NO) donors in pregnancies complicated by fetal growth restriction (FGR) METHODS: 26 women with a diagnosis of FGR were treated with transdermal patches of NO donors and plasma volume expansion. We compared the treated group to a control historical FGR untreated group of patients evaluated longitudinally. We obtained haemodynamic indices using UltraSonic Cardiac Output Monitor system. RESULTS: At enrolment, the two groups were similar in terms of maternal and haemodynamic characteristics. In the treated group, we found a significant increase in cardiac output, stroke volume and a decrease of systemic vascular resistance after therapy. No significant differences were found after two weeks in the untreated group. At birth the treated group also gave birth to babies with higher birth weight centile. CONCLUSIONS: Despite the observation nature of the data, the combined therapeutic approach of NO donor administration and plasma volume expansion in FGR significantly improves maternal hemodynamic indices

Activated T cells sustain myeloid-derived suppressor cell-mediated immune suppression

The expansion of myeloid-derived suppressor cells (MDSCs), a suppressive population able to hamper the immune response against cancer, correlates with tumor progression and overall survival in several cancer types. We have previously shown that MDSCs can be induced in vitro from precursors present in the bone marrow and observed that these cells are able to actively proliferate in the presence of activated T cells, whose activation level is critical to drive the suppressive activity of MDSCs. Here we investigated at molecular level the mechanisms involved in the interplay between MDSCs and activated T cells. We found that activated T cells secrete IL-10 following interaction with MDSCs which, in turn, activates STAT3 phosphorylation on MDSCs then leading to B7-H1 expression. We also demonstrated that B7-H1+ MDSCs are responsible for immune suppression through a mechanism involving ARG-1 and IDO expression. Finally, we show that the expression of ligands B7-H1 and MHC class II both on in vitro-induced MDSCs and on MDSCs in the tumor microenvironment of cancer patients is paralleled by an increased expression of their respective receptors PD-1 and LAG-3 on T cells, two inhibitory molecules associated with T cell dysfunction. These findings highlight key molecules and interactions responsible for the extensive cross-talk between MDSCs and activated T cells that are at the basis of immune suppression

Melanoma-restricted genes

Human metastatic cutaneous melanoma has gained a well deserved reputation for its immune responsiveness. The reason(s) remain(s) unknown. We attempted previously to characterize several variables that may affect the relationship between tumor and host immune cells but, taken one at the time, none yielded a convincing explanation. With explorative purposes, high-throughput technology was applied here to portray transcriptional characteristics unique to metastatic cutaneous melanoma that may or may not be relevant to its immunogenic potential. Several functional signatures could be identified descriptive of immune or other biological functions. In addition, the transcriptional profile of metastatic melanoma was compared with that of primary renal cell cancers (RCC) identifying several genes co-coordinately expressed by the two tumor types. Since RCC is another immune responsive tumor, commonalities between RCC and melanoma may help untangle the enigma of their potential immune responsiveness. This purely descriptive study provides, therefore, a map for the investigation of metastatic melanoma in future clinical trials and at the same time may invite consideration of novel therapeutic targets