Tumor-associated and immunochemotherapy-dependent long-term alterations of the peripheral blood NK cell compartment in DLBCL patients

Natural Killer (NK) cells are a key component of tumor immunosurveillance and thus play an important role in rituximab-dependent killing of lymphoma cells via an antibody-dependent cellular cytotoxicity (ADCC) mechanism. We evaluated the phenotypic and functional assets of peripheral blood NK cell subsets in 32 newly-diagnosed diffuse large B-cell lymphoma (DLBCL) patients and in 27 healthy controls. We further monitored long-term modifications of patient NK cells for up to 12 months after rituximab-based immunochemotherapy. At diagnosis, patients showed a higher percentage of CD56dim and CD16C NK cells, and a higher frequency of GrzBC cells in CD56dim, CD56bright, and CD16C NK cell subsets than healthy controls. Conversely, DLBCL NK cell killing and interferon g (IFNg) production capability were comparable to those derived from healthy subjects. Notably, NK cells from refractory/relapsed patients exhibited a lower “natural” cytotoxicity. A marked and prolonged therapy-induced reduction of both “natural” and CD16- dependent NK cytotoxic activities was accompanied by the down-modulation of CD16 and NKG2D activating receptors, particularly in the CD56dim subset. However, reduced NK cell killing was not associated with defective lytic granule content or IFNg production capability. This study firstly describes tumor-associated and therapy-induced alterations of the systemic NK cell compartment in DLBCL patients. As these alterations may negatively impact rituximab-based therapy efficacy, our work may provide useful information for improving immunochemotherapeutic strategies

Work‒family interface in the context of career success: A qualitative inquiry

Work–family researchers are increasingly recognizing the need to expand their focus to advance the field. One population largely neglected by work‒family researchers is individuals who have been extremely successful in their careers. In addition, organizational career scholars have largely neglected the interplay between employees’ work and family lives. This study contributes to the work‒family literature by studying work‒family interface (WFI) in the context of career success. We sought to explore the lived experiences of 28 distinguished professors who are among the top 2‒5% scholars in their field, to provide an in-depth understanding of their WFI and the prominent factors affecting it over their careers. Our findings have theoretical implications for both work‒family and career success literature

Interplay between cell adhesion and growth factor receptors: from the plasma membrane to the endosomes

The emergence of multicellular animals could only take place once evolution had produced molecular mechanisms for cell adhesion and communication. Today, all metazoans express integrin-type adhesion receptors and receptors for growth factors. Integrins recognize extracellular matrix proteins and respective receptors on other cells and, following ligand binding, can activate the same cellular signaling pathways that are regulated by growth factor receptors. Recent reports have indicated that the two receptor systems also collaborate in many other ways. Here, we review the present information concerning the role of integrins as assisting growth factor receptors and the interplay between the receptors in cell signaling and in the orchestration of receptor recycling

A liquid profession: An ecological approach to the theory and knowledge that underpin the practice of public relations

This is a conceptual essay that explores the concept of knowledge as it relates to PR. It suggests an ecological knowledge architecture as a lens through which to understand the theories and concepts that support practice. It does so by drawing on the work of Zygmunt Bauman and his reflections on liquid modernity to inform and shape thinking and uses it as a thread to help synthesise scholarship from PR literature, knowledge and career scholarship and debates around professionalisation. It argues that by sub-dividing knowledge into explanatory, interventionist and practice principles greater clarity can be given to the know-how (functional skills) and know-that (theoretical knowledge) of PR. Additionally, by overlaying a postmodernist and liquid concept to this tripartite division of knowledge PR can be well placed to take advantage of the change in careers and capabilities necessary for work in the twenty-first century

Selective phenotypical and functional alterations of peripheral blood immune cells in neo-diagnosed patients with Diffuse Large B cell Lymphoma (DLBCL)

PURPOSE: To investigate the impact of lymphoid tumor presence on the asset of the systemic immune compartment. METHODS: Multiparameter FACS analysis and in vitro cytotoxicity assay were used to evaluate: 1) natural and CD16-mediated NK cytotoxic functions; 2) relative and absolute frequency, and 3) cytotoxic and IFN γ production capabilities of the main leukocyte subsets, in a cohort of 32 DLBCL patients at diagnosis and 27 healthy, age- and sex-matched controls. RESULTS: Patients showed a higher absolute monocyte number, and a lower lymphocyte count, mostly due to the selective diminution of CD4+ T cells (but not of Treg), and B lymphocytes. Accordingly, lymphocyte/monocyte and CD4/CD8 ratios decreased, while NK percentage increased. The phenotypically skewed profile of PBL associated with functional alterations, as: 1) IFN γ+ cells were increased among CD4+ and CD8+ T cell subsets, but not in CD56+ T and CD3-CD56+ NK cell populations; 2) a higher frequency of Granzyme B+ cells characterized (CD4+ and CD8+) T and (CD56bright and CD56dim) NK cell subsets; noteworthy, natural and CD16-dependent NK cytotoxic activities were unchanged. IL-6 and IL-10 plasma levels were significantly higher in DLBCL. Selected alterations of patients' immunological profile differently correlated with the DLBCL Germinal Center B (GCB) vs non GCB-type and with the presence of bulky disease or the involvement of extra-nodal sites. DISCUSSION: Our findings show a deeply altered phenotypic and functional PBMC profile in newly-diagnosed DLBCL patients, with the lymphocyte compartment showing traits of chronic activation; moreover, distinct immunological alterations correlated with tumor histological subtype and clinical features. CONCLUSION: These results suggest that tumor presence deeply affects the immune status of the host, at the systemic level, in the context of the immune system/tumor cross-talk; they could be of relevance in the perspective of chemoimmunotherapeutical strategies.PURPOSE: To investigate the impact of lymphoid tumor presence on the asset of the systemic immune compartment. METHODS: Multiparameter FACS analysis and in vitro cytotoxicity assay were used to evaluate: 1) natural and CD16-mediated NK cytotoxic functions; 2) relative and absolute frequency, and 3) cytotoxic and IFN γ production capabilities of the main leukocyte subsets, in a cohort of 32 DLBCL patients at diagnosis and 27 healthy, age- and sex-matched controls. RESULTS: Patients showed a higher absolute monocyte number, and a lower lymphocyte count, mostly due to the selective diminution of CD4+ T cells (but not of Treg), and B lymphocytes. Accordingly, lymphocyte/monocyte and CD4/CD8 ratios decreased, while NK percentage increased. The phenotypically skewed profile of PBL associated with functional alterations, as: 1) IFN γ+ cells were increased among CD4+ and CD8+ T cell subsets, but not in CD56+ T and CD3-CD56+ NK cell populations; 2) a higher frequency of Granzyme B+ cells char