Resilient Organizations in the Third Sector. Professionalized Membership Associations, Social Enterprises, Modern Hybrids

How do nonprofit organizations manage to survive? How are they able to adapt to changed environments without losing their distinctiveness? Fifteen case studies of nonprofit organizations operating across Europe tell us a story of how to make ends meet. The cases presented, identified and analyzed in the framework of the European Union-funded research project Third Sector Impact (TSI) (Enjolras et al. 2018)1 , are organizations that are confronted with an increasingly hostile environment in terms of the availability of resources and co-operation with government. Some of them, particularly those in Southern Europe and in the U.K., suffer from austerity politics and financial cutbacks; some are struggling for recognition on the part of the general public or the government. This is still the case especially in post-socialist countries. The goal of this e-book is to highlight that, despite the fact that third sector organizations (TSOs) are currently confronted with a thoroughly changed environment, they continue contributing to the well-being of citizens in Europe through their innovativeness and by providing services as well as avenues for active participation. The book focuses on case studies of organizations that managed to find a way to adapt to a significantly changed organizational environment by alluding to the power of resilience.How do nonprofit organizations manage to survive? How are they able to adapt to changed environments without losing their distinctiveness? Fifteen case studies of nonprofit organizations operating across Europe tell us a story of how to make ends meet. The cases presented, identified and analyzed in the framework of the European Union-funded research project Third Sector Impact (TSI) (Enjolras et al. 2018)1 , are organizations that are confronted with an increasingly hostile environment in terms of the availability of resources and co-operation with government. Some of them, particularly those in Southern Europe and in the U.K., suffer from austerity politics and financial cutbacks; some are struggling for recognition on the part of the general public or the government. This is still the case especially in post-socialist countries. The goal of this e-book is to highlight that, despite the fact that third sector organizations (TSOs) are currently confronted with a thoroughly changed environment, they continue contributing to the well-being of citizens in Europe through their innovativeness and by providing services as well as avenues for active participation. The book focuses on case studies of organizations that managed to find a way to adapt to a significantly changed organizational environment by alluding to the power of resilience

IDO1 + Paneth cells promote immune escape of colorectal cancer

Abstract: Tumors have evolved mechanisms to escape anti-tumor immunosurveillance. They limit humoral and cellular immune activities in the stroma and render tumors resistant to immunotherapy. Sensitizing tumor cells to immune attack is an important strategy to revert immunosuppression. However, the underlying mechanisms of immune escape are still poorly understood. Here we discover Indoleamine-2,3-dioxygenase-1 (IDO1)+ Paneth cells in the stem cell niche of intestinal crypts and tumors, which promoted immune escape of colorectal cancer (CRC). Ido1 expression in Paneth cells was strictly Stat1 dependent. Loss of IDO1+ Paneth cells in murine intestinal adenomas with tumor cell-specific Stat1 deletion had profound effects on the intratumoral immune cell composition. Patient samples and TCGA expression data suggested corresponding cells in human colorectal tumors. Thus, our data uncovered an immune escape mechanism of CRC and identify IDO1+ Paneth cells as a target for immunotherapy

IDO1 + Paneth cells promote immune escape of colorectal cancer

Abstract: Tumors have evolved mechanisms to escape anti-tumor immunosurveillance. They limit humoral and cellular immune activities in the stroma and render tumors resistant to immunotherapy. Sensitizing tumor cells to immune attack is an important strategy to revert immunosuppression. However, the underlying mechanisms of immune escape are still poorly understood. Here we discover Indoleamine-2,3-dioxygenase-1 (IDO1)+ Paneth cells in the stem cell niche of intestinal crypts and tumors, which promoted immune escape of colorectal cancer (CRC). Ido1 expression in Paneth cells was strictly Stat1 dependent. Loss of IDO1+ Paneth cells in murine intestinal adenomas with tumor cell-specific Stat1 deletion had profound effects on the intratumoral immune cell composition. Patient samples and TCGA expression data suggested corresponding cells in human colorectal tumors. Thus, our data uncovered an immune escape mechanism of CRC and identify IDO1+ Paneth cells as a target for immunotherapy

Long-Term Cytomegalovirus Infection Leads to Significant Changes in the Composition of the CD8(+) T-Cell Repertoire, Which May Be the Basis for an Imbalance in the Cytokine Production Profile in Elderly Persons

In spite of the present belief that latent cytomegalovirus (CMV) infection drives CD8(+) T-cell differentiation and induces premature immune senescence, no systematic studies have so far been performed to compare phenotypical and functional changes in the CD8(+) T-cell repertoire in CMV-infected and noninfected persons of different age groups. In the present study, number, cytokine production, and growth potential of naïve (CD45RA(+) CD28(+)), memory (CD45RA(−) CD28(+)), and effector (CD45RA(+) CD28(−) or CD45RA(−) CD28(−)) CD8(+) T cells were analyzed in young, middle-aged, and elderly clinically healthy persons with a positive or negative CMV antibody serology. Numbers and functional properties of CMVpp65(495-503)-specific CD8(+) T cells were also studied. We demonstrate that aging as well as CMV infection lead to a decrease in the size of the naïve CD8(+) T-cell pool but to an increase in the number of CD8(+) effector T cells, which produce gamma interferon but lack substantial growth potential. The size of the CD8(+) memory T-cell population, which grows well and produces interleukin-2 (IL-2) and IL-4, also increases with aging, but this increase is missing in CMV carriers. Life-long latent CMV infection seems thus to diminish the size of the naïve and the early memory T-cell pool and to drive a Th1 polarization within the immune system. This can lead to a reduced diversity of CD8 responses and to chronic inflammatory processes which may be the basis of severe health problems in elderly persons

Post-thymic regulation of CD5 levels in human memory T cells is inversely associated with the strength of responsiveness to interleukin-15

Immunologic memory is a critical feature of the adaptive immune system to fight recurrent infections. However, the mechanisms that shape the composition and function of the human memory T-cell pool remain incompletely understood. We here demonstrate that post-thymic human T-cell differentiation was associated with the downregulation, but not loss, of the inhibitory molecule CD5. The sensitivity of human CD8+ and CD4+ memory T cells to interleukin (IL)–15 was inversely associated with the level of CD5 expression. CD5 expression was downregulated by IL-15–mediated signaling in vitro and CD5lo memory T cells accumulated in the bone marrow. Persistent antigenic stimulation, as in the case of cytomegalovirus infection and rheumatoid arthritis (RA), was also associated with an increased number of CD5lo memory T cells. In conclusion, CD5 may be a useful marker to identify memory T-cell subsets with distinct responsiveness to the homeostatic cytokine IL-15

IDO1 + Paneth cells promote immune escape of colorectal cancer

Abstract: Tumors have evolved mechanisms to escape anti-tumor immunosurveillance. They limit humoral and cellular immune activities in the stroma and render tumors resistant to immunotherapy. Sensitizing tumor cells to immune attack is an important strategy to revert immunosuppression. However, the underlying mechanisms of immune escape are still poorly understood. Here we discover Indoleamine-2,3-dioxygenase-1 (IDO1)+ Paneth cells in the stem cell niche of intestinal crypts and tumors, which promoted immune escape of colorectal cancer (CRC). Ido1 expression in Paneth cells was strictly Stat1 dependent. Loss of IDO1+ Paneth cells in murine intestinal adenomas with tumor cell-specific Stat1 deletion had profound effects on the intratumoral immune cell composition. Patient samples and TCGA expression data suggested corresponding cells in human colorectal tumors. Thus, our data uncovered an immune escape mechanism of CRC and identify IDO1+ Paneth cells as a target for immunotherapy