”It is a long process and it will take time but it does not mean that it is impossible – it is possible!” : experiences of workers from three projects in prevention of honour-related violence among patriarchal immigrant communities in Finland

In this study the focus is on examining the ways and methods to prevent honour-related violence among patriarchal immigrant communities. The phenomenon is proved to appear in Finland and hence it is important to find preventative solution-centred tools for it. The study also aims at addressing the challenges concerning the work as well as finding the developing points for future work in Finland. The data was collected from the main workers of three projects which focus on their work on prevention of HRV. The research is qualitative and semi-structured thematic interviews were used to collect the data. One of the key findings of the study is the use of dialogue, whether using some functional method or a more traditional method. Through the dialogue and knowledge increase the thought patterns can be challenged as alternative ways to think and act can be offered. These are hoped to be activated in mind when some honour issue appears. The study results speak for an indirect way of addressing the issue among the target group so that people would not be driven away. Cultural sensitivity and gender sensitivity seem to be good approaches in work. It is highlighted that the real change will only start from inside of communities which should be kept in mind at work. Certain challenges stand out in results like unreachability of some people, the uncertainty of the work, integration problems as well as power and position changes inside families. These challenges point out also how the work could be developed in future like establishing more channels for reaching people and strengthening the integration process of different family members. The awareness and training for professionals and impact on the authorities to be able to develop the work is strongly recommended

Interaktion som mål och medel i FinTandem

fi=vertaisarvioitu|en=peerReviewed

Clinical Impact of Immune Cells and Their Spatial Interactions in Diffuse Large B-Cell Lymphoma Microenvironment

Purpose: Tumor-infiltrating immune cells have prognostic sig-nificance and are attractive therapeutic targets. Yet, the clinical significance of their spatial organization and phenotype in diffuse large B-cell lymphoma (DLBCL) is unclear. Experimental Design: We characterized T cells, macrophages, and their spatial interactions by multiplex IHC (mIHC) in 178 patients with DLBCL and correlated the data with patient demo-graphics and survival. We validated the findings on gene expression data from two external DLBCL cohorts comprising 633 patients. Results: Macrophage and T-cell contents divided the samples into T cell-inflamed (60%) and noninflamed (40%) subgroups. The T cell-inflamed lymphoma microenvironment (LME) was also rich in other immune cells, defining immune hot phenotype, which did not as such correlate with outcome. However, when we divided the patients according to T-cell and macrophage contents, LME char-acterized by high T-cell/low macrophage content or a correspond-ing gene signature was associated with superior survival [5-year overall survival (OS): 92.3% vs. 74.4%, P = 0.036; 5-year progres-sion-free survival (PFS): 92.6% vs. 69.8%, P = 0.012]. High pro-portion of PD -L1-and TIM3-expressing CD163- macrophages in the T cell-inflamed LME defined a group of patients with poor outcome [OS: HR = 3.22, 95% confidence interval (CI), 1.63-6.37, P-adj = 0.011; PFS: HR = 2.76, 95% CI, 1.44-5.28, P-adj = 0.016]. Furthermore, PD-L1 and PD-1 were enriched on macrophages interacting with T cells. Conclusions: Our data demonstrate that the interplay between macrophages and T cells in the DLBCL LME is immune checkpoint dependent and clinically meaningful.Peer reviewe

Adverse prognostic impact of regulatory T-cells in testicular diffuse large B-cell lymphoma

Objectives Testicular diffuse large B-cell lymphoma (T-DLBCL) is a rare and aggressive extranodal lymphoma. We have previously shown that high content of tumor-infiltrating lymphocytes (TILs) and PD-1 expressing TILs associate with better survival in T-DLBCL. In this study, we have further characterized distinct TIL subtypes and their proportions in association with patient demographics and survival. Methods We used multiplex immunohistochemistry to characterize TIL phenotypes, including cytotoxic T-cells (CTLs; CD8(+), OX40(+), Granzyme B+, Ki-67(+), LAG-3(+), TIM-3(+), PD-1(+)), CD4(+)T-cells (CD3(+), CD4(+), TIM-3(+), LAG-3(+)), regulatory T-cells (Tregs; CD3(+), CD4(+), FoxP3(+)), and T helper 1 cells (Th1; CD3(+), CD4(+), T-bet(+)) in 79 T-DLBCLs, and correlated the findings with patient demographics and outcome. Results We observed a substantial variation in TIL phenotypes between the patients. The most prominent CD8(+)TILs were Ki-67(+)and TIM-3(+)CTLs, whereas the most prominent CD4(+)TILs were FoxP3(+)Tregs. Despite the overall favorable prognostic impact of high TIL content, we found a subpopulation of T-bet(+)FoxP3(+)Tregs that had a significant adverse impact on survival. Lower content of CTLs with activated or exhausted phenotypes correlated with aggressive clinical features. Conclusions Our results demonstrate significant variation in TIL phenotypes and emphasize the adverse prognostic impact of Tregs in T-DLBCL.Peer reviewe

Prognostic Impact of Tumor-Associated Macrophages on Survival Is Checkpoint Dependent in Classical Hodgkin Lymphoma

Tumor microenvironment and immune escape affect pathogenesis and survival in classical Hodgkin lymphoma (cHL). While tumor-associated macrophage (TAM) content has been associated with poor outcomes, macrophage-derived determinants with clinical impact have remained undefined. Here, we have used multiplex immunohistochemistry and digital image analysis to characterize TAM immunophenotypes with regard to expression of checkpoint molecules programmed cell death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO-1) from the diagnostic tumor tissue samples of 130 cHL patients, and correlated the findings with clinical characteristics and survival. We show that a large proportion of TAMs express PD-L1 (CD68+, median 32%; M2 type CD163+, median 22%), whereas the proportion of TAMs expressing IDO-1 is lower (CD68+, median 5.5%; CD163+, median 1.4%). A high proportion of PD-L1 and IDO-1 expressing TAMs from all TAMs (CD68+), or from CD163+ TAMs, is associated with inferior outcome. In multivariate analysis with age and stage, high proportions of PD-L1+ and IDO-1+ TAMs remain independent prognostic factors for freedom from treatment failure (PD-L1+CD68+/CD68+, HR = 2.63, 95% CI 1.17–5.88, p = 0.019; IDO-1+CD68+/CD68+, HR = 2.48, 95% CI 1.03–5.95, p = 0.042). In contrast, proportions of PD-L1+ tumor cells, all TAMs or PD-L1− and IDO-1− TAMs are not associated with outcome. The findings implicate that adverse prognostic impact of TAMs is checkpoint-dependent in cHL

Correlates of different facets and components of betadiversity in stream organisms

peerReviewe

Checkpoint protein expression in the tumor microenvironment defines the outcome of classical Hodgkin lymphoma patients

Emerging evidence indicates a major impact for the tumor microenvironment (TME) and immune escape in the pathogenesis and clinical course of classical Hodgkin lymphoma (cHL). We used gene expression profiling (n = 88), CIBERSORT, and multiplex immunohistochemistry (n = 131) to characterize the immunoprofile of cHL TME and correlated the findings with survival. Gene expression analysis divided tumors into subgroups with T cell-inflamed and -noninflamed TME. Several macrophage-related genes were upregulated in samples with the non-T cell-inflamed TME, and based on the immune cell proportions, the samples clustered according to the content of T cells and macrophages. A cluster with high proportions of checkpoint protein (programmed cell death protein 1, PD-1 ligands, indoleamine 2,3 dioxygenase 1, lymphocyte-activation gene 3, and T-cell immunoglobulin and mucin domain containing protein 3) positive immune cells translated to unfavorable overall survival (OS) (5-year OS 76% vs 96%; P = .010) and remained an independent prognostic factor for OS in multivariable analysis (HR, 4.34; 95% CI, 1.05-17.91; P = .043). cHL samples with high proportions of checkpoint proteins overexpressed genes coding for cytolytic factors, proposing paradoxically that they were immunologically active. This checkpoint molecule gene signature translated to inferior survival in a validation cohort of 290 diagnostic cHL samples (P < .001) and in an expan-sion cohort of 84 cHL relapse samples (P = .048). Our findings demonstrate the impact of T cell-and macrophage-mediated checkpoint system on the survival of patients with cHL.Peer reviewe