BACKGROUND: Despite recent improvement in the treatment of malignant melanoma by immune-checkpoint inhibitors, the disease can progress due to an immunosuppressive tumor microenvironment (TME) mainly represented by myeloid-derived suppressor cells (MDSC). However, the relative contribution of the polymorphonuclear (PMN) and monocytic (M) MDSC subsets to melanoma progression is not clear. Here, we compared both subsets regarding their immunosuppressive capacity and recruitment mechanisms. Furthermore, we inhibited PMN-MDSC migration in vivo to determine its effect on tumor progression. METHODS: Using the RET transgenic melanoma mouse model, we investigated the immunosuppressive function of MDSC subsets and chemokine receptor expression on these cells. The effect of CXCR2 inhibition on PMN-MDSC migration and tumor progression was studied in RET transgenic mice and in C57BL/6 mice after surgical resection of primary melanomas. RESULTS: Immunosuppressive capacity of intratumoral M- and PMN-MDSC was comparable in melanoma bearing mice. Anti-CXCR2 therapy prolonged survival of these mice and decreased the occurrence of distant metastasis. Furthermore, this therapy reduced the infiltration of melanoma lesions and pre-metastatic sites with PMN-MDSC that was associated with the accumulation of natural killer (NK) cells. CONCLUSIONS: We provide evidence for the tumor-promoting properties of PMN-MDSC as well as for the anti-tumor effects upon their targeting in melanoma bearing mice.
BACKGROUND: Trained local screeners assessed the mental-health status of male and female students in Northern Ugandan schools. The study aimed to disclose potential differences in mental health-related impairment in two groups, former child soldiers (n = 354) and other war-affected youth (n = 489), as well as to separate factors predicting mental suffering in learners. METHODS: Participants were randomly selected. We used the Post-Traumatic Diagnostic Scale to assess symptoms of post-traumatic stress disorder (PTSD) and for potential depression the respective section of the Hopkins Symptom Checklist with a locally validated cut-off. RESULTS: Almost all respondents had been displaced at least once in their life. 30% of girls and 50% of the boys in the study reported past abduction history. Trauma exposure was notably higher in the group of abductees. In former child soldiers, a PTSD rate of 32% was remarkably higher than that for non-abductees (12%). Especially in girls rates of potential depression were double those in the group of former abductees (17%) than in the group of non-abductees (8%). In all groups, trauma exposure increased the risk of developing PTSD. A path-analytic model for developing PTSD and potential depression revealed both previous trauma exposure as well as duration of abduction to have significant influences on trauma-related mental suffering. Findings also suggest that in Northern Ugandan schools trauma spectrum disorders are common among war-affected learners. CONCLUSIONS: Therefore, it is suggested the school context should be used to provide mental-health support structures within the education system for war-affected youth at likely risk of developing war-related mental distress.
