Induction of tumour-specific CD8+ cytotoxic T lymphocytes by tumour lysate-pulsed autologous dendritic cells in patients with uterine serous papillary cancer

Uterine serous papillary carcinoma is a highly aggressive variant of endometrial cancer histologically similar to high grade ovarian cancer. Unlike ovarian cancer, however, it is a chemoresistant disease from onset, with responses to combined cisplatinum-based chemotherapy in the order of 20% and an extremely poor prognosis. In this study, we demonstrate that tumour lysate-pulsed autologous dendritic cells can elicit a specific CD8+ cytotoxic T lymphocyte response against autologous tumour target cells in three patients with uterine serous papillary cancer. CTL from patients 1 and 2 expressed strong cytolytic activity against autologous tumour cells, did not lyse autologous lymphoblasts or autologous EBV-transformed cell lines, and were variably cytotoxic against the NK-sensitive cell line K-562. Patient 3 CD8+ T cells expressed a modest but reproducible cytotoxicity against autologous tumour cells only at the time of the first priming. Further priming attempts with PBL collected from patient 3 after tumour progression in the lumboaortic lymph nodes were unsuccesful. Cytotoxicity against autologous tumour cells could be significantly inhibited by anti-HLA class I (W6/32) and anti-LFA-1 MAbs. Highly cytotoxic CD8+ T cells from patients 1 and 2 showed a heterogeneous CD56 expression while CD56 was not expressed by non-cytotoxic CD8+ T cells from patient 3. Using two colour flow cytometric analysis of intracellular cytokine expression at the single cell level, a striking dominance of IFN-γ expressors was detectable in CTL populations of patients 1 and 2 while in patient 3 a dominant population of CD8+ T cells expressing IL-4 and IL-10 was consistently detected. Taken together, these data demonstrate that tumour lysate-pulsed DC can be an effective tool in inducing uterine serous papillary cancer-specific CD8+ CTL able to kill autologous tumour cells in vitro. However, high levels of tumour specific tolerance in some patients may impose a significant barrier to therapeutic vaccination. These results may have important implications for the treatment in the adjuvant setting of uterine serous papillary cancer patients with active or adoptive immunotherapy

Making Sense of War Memories

This article analyzes the war memories and processes of meaning-making of Dutch veterans who returned to places related to their deployment in former Yugoslavia in the 1990s. It argues that the incentive to return can be found in the difficulties that veterans have in assigning positive meaning to their deployment because existing collective and cultural memories about the war and the genocide in Srebrenica do not align with many of the veterans’ experiences during and after the war. In the analysis of interviews conducted with seventeen Dutch veterans, attention is paid to their wartime memories, motivation to return, and experiences during the return trips. Returning to former places of deployment provides a way to reconcile memories, especially traumatic ones. The building of these memories passes through several phases: introspection; opening up to family, friends, and relatives; and helping others.</p

Nurses in the lead

Background: Transitions in healthcare delivery, such as the rapidly growing numbers of older people and increasing social and healthcare needs, combined with nursing shortages has sparked renewed interest in differentiations in nursing staff and skill mix. Policy attempts to implement new competency frameworks and job profiles often fails for not serving existing nursing practices. This study is aimed to understand how licensed vocational nurses (VNs) and nurses with a Bachelor of Science degree (BNs) shape distinct nursing roles in daily practice. Methods: A qualitative study was conducted in four wards (neurology, oncology, pneumatology and surgery) of a Dutch teaching hospital. Various ethnographic methods were used: shadowing nurses in daily practice (65h), observations and participation in relevant meetings (n=56), informal conversations (up to 15 h), 22 semi-structured interviews and member-checking with four focus groups (19 nurses in total). Data was analyzed using thematic analysis. Results: Hospital nurses developed new role distinctions in a series of small-change experiments, based on action and appraisal. Our findings show that: (1) this developmental approach incorporated the nurses’ invisible work; (2) nurses’ roles evolved through the accumulation of small changes that included embedding the new routines in organizational structures; (3) the experimental approach supported the professionalization of nurses, enabling them to translate national legislation into hospital policies and supporting the nurses’ (bottom-up) evolution of practices. The new roles required the special knowledge and skills of Bachelor-trained nurses to support healthcare quality improvement and connect the patients’ needs to organizational capacity. Conclusions: Conducting small-change experiments, anchored by action and appraisal rather than by design, clarified the distinctions between vocational and Bachelor-trained nurses. The process stimulated personal leadership and boosted the responsibility nurses feel for their own development and the nursing profession in general. This study indicates that experimental nursing role development provides opportunities for nursing professionalization and gives nurses, managers and policymakers the opportunity of a ‘two-way-window’ in nursing role development, aligning policy initiatives with daily nursing practices.</p

Role of Dutch internal policy advisors in a hospital quality improvement programme and their influence on nurses' role development

Objective Nurses are vital in providing and improving quality of care. To enhance the quality improvement (QI) competencies of nurses, hospitals in the Netherlands run developmental programmes generally led by internal policy advisors (IPAs). In this study, we identify the roles IPAs play during these programmes to enhance the development of nurses' QI competencies and studied how these roles influenced nurses and management. Design An exploratory ethnographical study comprising observations, informal conversations, semistructured interviews, focus groups and a strategy evaluation meeting. Setting A teaching hospital in an urban region in the Netherlands. Participants IPAs (n=7) in collaboration with four teams of nurses (n=131), team managers (n=4), senior managers (n=4) and the hospital director (n=1). Results We identified five distinct advisory roles that IPAs perform in the hospital programme: gatekeeper, connector, converter, reflector and implementer. In describing these roles, we provide insights into how IPAs help nurses to develop QI competencies. The IPA's professional background was a driving force for nurses' QI role development. However, QI development was threatened if IPAs lost sight of different stakeholders' interests and consequently lost their credibility. QI role development among nurses was also threatened if the IPA took on all responsibility instead of delegating it timely to managers and nurses. Conclusions We have shown how IPAs' professional background and advisory knowledge connect organisational, managerial and professional aims and interests to enhance professionalisation of nurses.</p