Chronic T cell receptor stimulation unmasks NK receptor signaling in peripheral T cell lymphomas via epigenetic reprogramming.

Peripheral T cell lymphomas (PTCLs) represent a significant unmet medical need with dismal clinical outcomes. The T cell receptor (TCR) is emerging as a key driver of T lymphocyte transformation. However, the role of chronic TCR activation in lymphomagenesis and in lymphoma cell survival is still poorly understood. Using a mouse model, we report that chronic TCR stimulation drove T cell lymphomagenesis, whereas TCR signaling did not contribute to PTCL survival. The combination of kinome, transcriptome, and epigenome analyses of mouse PTCLs revealed a NK cell-like reprogramming of PTCL cells with expression of NK receptors (NKRs) and downstream signaling molecules such as Tyrobp and SYK. Activating NKRs were functional in PTCLs and dependent on SYK activity. In vivo blockade of NKR signaling prolonged mouse survival, demonstrating the addiction of PTCLs to NKRs and downstream SYK/mTOR activity for their survival. We studied a large collection of human primary samples and identified several PTCLs recapitulating the phenotype described in this model by their expression of SYK and the NKR, suggesting a similar mechanism of lymphomagenesis and establishing a rationale for clinical studies targeting such molecules

More than competition: exploring stakeholder identities at a grassroots cause-related sporting event

The purpose of this paper is to (a) explore stakeholder identities of a grassroots cause-related sporting event; and (b) gain a better understanding of how identities are related to stakeholder development, support of the event, and future intentions. We used a mixed methods research design that consisted of two studies: qualitative followed by quantitative. Study 1 explored stakeholder identities and how they are related to stakeholder development and support of the event, and Study 2 examined how future intentions regarding attendance, donations, and sponsor support differ based on levels of stakeholder identity. Sports marketing and non-profit management literature streams as well as identity theory and social capital theory informed our studies. The National Kidney Foundation Surf Festival was selected because it is a grassroots cause-related sporting event with financial success over the last two decades. In addition, a surf contest, an action sport, is a unique sport setting in the nonprofit sector, which offers insight to marketers seeking to target subcultures. The findings of the qualitative study revealed three identities relevant to participants: sport subculture, community, and cause. A framework emerged from the data that illustrated how these identities unite together to generate social capital, which is linked to effective volunteer and sponsorship management. Quantitative analysis through survey data provided further evidence of the impact of identification with a cause-related sport activity on consumer outcomes. Results indicated attendees with high surf-related identity are more likely to attend future Surf Festivals, have higher intentions to donate to the cause, and have higher sponsor purchase intentions compared to those with low self-identity with the sport subculture. The conclusion discusses implications, framing the findings through the intersection of the sports marketing and non-profit sector industries, and provides suggestions for future research.Ye

Investigating the correlation between customer retention programs of CRM and customer retention in e-banking context

In this study, considering different perspectives and concepts about customer relationship management (CRM), we try to investigate the significance of the correlation between each of the customer retention programs of CRM (loyalty programs, customer service, customization, and community) and customer retention. Data from 286 top bank managers of two governmental and two private Iranian bank branches were gathered in a field survey. The results of data analysis show the positive and significant correlation between each of the customer retention programs of CRM and customer retention. The study also finds the most significant correlation between customer service and customer retention. © 2011 Springer-Verlag

Genetic and antibody-mediated reprogramming of natural killer cell missing-self recognition in vivo

Natural killer (NK) cells are lymphocytes of the innate immune system able to recognize and kill tumors lacking self-MHC class I molecules. This “missing-self” recognition is mediated by the lack of engagement of MHC class I-specific inhibitory NK cell receptors that include the killer cell Ig-like receptors (KIR) in humans and Ly49 molecules in mice. A promising immunotherapeutic strategy against MHC class I+ cancer cells is to block NK cell inhibitory receptors using monoclonal antibodies (mAb). However, interactions between MHC class I molecules and their inhibitory receptors are also required for the acquisition of NK cell functional competence, a process referred as to “education.” In addition, inhibitory receptors are involved in self-tolerance on educated NK cells. Here, we developed a preclinical mouse model in which all NK cells are educated by a single transgenic inhibitory receptor, human KIR2DL3, through the engagement with its HLA-Cw3 ligand. This approach revealed that NK cells could be reprogrammed to control the development of mouse syngenic tumors in vivo. Moreover, in vivo anti-KIR mAb treatment induced the killing of HLA+ target cells without breaking self-tolerance. Finally, the long-term infusion of anti-KIR mAb neither abolished NK cell education nor tumor cell recognition. Therefore, these results strongly support the use of inhibitory receptor blockade in cancer patients