IL-22 has been identified as a cancer-promoting cytokine that is secreted by infiltrating immune cells in several cancer models. We hypothesized that IL-22 regulation would occur at the interface between cancer cells and immune cells. Breast and lung cancer cells of murine and human origin induced IL-22 production from memory CD4 T cells. In the present study, we found that IL-22 production in humans is dependent on activation of the NLRP3 inflammasome with the subsequent release of IL-1β from both myeloid and T cells. IL-1 receptor signaling via the transcription factors AhR and RORγt in T cells was necessary and sufficient for IL-22 production. In these settings, IL-1 induced IL-22 production from a mixed T helper cell population comprised of Th1, Th17, and Th22 cells, which was abrogated by the addition of anakinra. We confirmed these findings in vitro and in vivo in two murine tumor models, in primary human breast and lung cancer cells, and in deposited expression data. Relevant to ongoing clinical trials in breast cancer, we demonstrate here that the IL-1 receptor antagonist anakinra abrogates IL-22 production and reduces tumor growth in a murine breast cancer model. Thus, we describe here a previously unrecognized mechanism by which cancer cells induce IL-22 production from memory CD4 T cells via activation of the NLRP3 inflammasome and the release of IL-1β to promote tumor growth. These findings may provide the basis for therapeutic interventions that affect IL-22 production by targeting IL-1 activity.

BackgroundThere is partially conflicting evidence on the influence of the steroid hormones estrogen (E) and progesterone (P) on the development of ovarian cancer (OC). The aim of this study was to assess the expression of the receptor isoforms ER-α/-β and PR-A/-B in OC tissue and to analyze its impact on clinical and pathological features and patient outcome.Methods155 OC patients were included who had been diagnosed and treated between 1990 and 2002. Patient characteristics, histology and follow-up data were available. ER-α/-β and PR-A/-B expression were determined by immunohistochemistry.ResultsOC tissue was positive for ER-α/-β in 31.4% and 60.1% and PR-A/-B in 36.2% and 33.8%, respectively. We identified significant differences in ER-β expression related to the histological subtype (p=0.041), stage (p=0.002) and grade (p=0.011) as well as PR-A and tumor stage (p=0.03). Interestingly, median receptor expression for ER-α and PR-A/-B was significantly higher in G1 vs. G2 OC. Kaplan Meier analysis revealed a good prognosis for ER-α positive (p=0.039) and PR-B positive (p<0.001) OC. In contrast, ER-β negative OC had a favorable outcome (p=0.049). Besides tumor grade and stage, Cox-regression analysis showed PR-B to be an independent prognostic marker for patient survival (p=0.009, 95% CI 0.251-0.823, HR 0.455).ConclusionER-α/-β and PR-A/-B are frequently expressed in OC with a certain variability relating to histological subtype, grade and stage. Univariate analysis indicated a favorable outcome for ER-α positive and PR-B positive OC, while multivariate analysis showed PR-B to be the only independent prognostic marker for patient survival. In conclusion, ER and PR receptors may be useful targets for a more individualized OC therapy.

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BackgroundThe prevalence and detrimental health effects of intimate partner violence have resulted in international discussions and recommendations that health care professionals should screen women for intimate partner violence during general and antenatal health care visits. Due to the lack of discussion on routine or case-based inquiry for intimate partner violence during antenatal care in Germany, this study seeks to explore its acceptability among pregnant German women.MethodsA mixed methods approach was used, utilizing a self-administered survey on the acceptability of routine or case-based inquiry for intimate partner violence in a university hospital’s maternity ward in Munich and in-depth interviews with seven women who experienced violence during pregnancy.ResultsOf the 401 women who participated in the survey, 92 percent were in favor of routine or case-based inquiry for intimate partner violence during antenatal care. Acceptance of routine or case-based inquiry for intimate partner violence during antenatal care was significantly associated with women’s experiences of child sexual abuse, being young, less educated, single or divorced and smoking during pregnancy. Open-ended survey questions and in-depth interviews stressed adequate training for screening, sufficient time and provision of referral information as important conditions for routine or case-based inquiry for intimate partner violence.ConclusionsWomen in this study showed an overwhelming support for routine or case-based screening for intimate partner violence in antenatal care in Germany. Until adequate training is in place to allow providers to inquire for intimate partner violence in a professional manner, this study recommends that health care providers are made aware of the prevalence and health consequences of violence during pregnancy.

The use of PADM as an interface matrix for implant-based breast reconstruction yielded predictable and acceptable aesthetic and haptic results by preventing capsular contracture, rippling, implant malposition, soft-tissue thinning and failure of the silicone implant-based breast augmentation.