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Sperm develop from puberty in the seminiferous tubules, inside the blood-testis barrier to prevent their recognition as "non-self" by the immune system, and it is widely assumed that human sperm-specific proteins cannot access the circulatory or immune systems. Sperm-specific proteins aberrantly expressed in cancer, known as cancer-testis antigens (CTAs), are often pursued as cancer biomarkers and therapeutic targets based on the assumption they are neoantigens absent from the circulation in healthy men. Here, we identify a wide range of germ cell-derived and sperm-specific proteins, including multiple CTAs, that are selectively deposited by the Sertoli cells of the adult mouse and human seminiferous tubules into testicular interstitial fluid (TIF) that is "outside" the blood-testis barrier. From TIF, the proteins can access the circulatory- and immune systems. Disruption of spermatogenesis decreases the abundance of these proteins in mouse TIF, and a sperm-specific CTA is significantly decreased in TIF from infertile men, suggesting that exposure of certain CTAs to the immune system could depend on fertility status. The results provide a rationale for the development of blood-based tests useful in the management of male infertility and indicate CTA candidates for cancer immunotherapy and biomarker development that could show sex-specific and male-fertility-related responses.

Human testicular germ cell tumours commonly feature abundant infiltrating immune cells, most previously identified as T cells and macrophages. But what consequences come along with these changes within the tumour environment? In our study, in addition to immune-morphological analysis, the cytokine microenvironment of testicular cancers has been surveyed for the first time, performing RT-qPCR on human testicular biopsy samples. The results reveal significantly increased expression of pro-inflammatory cytokines in cancer samples relative to healthy tissue, as well as cytokines associated with B cells, whose presence can further be confirmed by immunohistochemistry. These ex vivo results suggest an exceptional involvement of B cells and pro-inflammatory cytokines in the immunopathology of testicular cancer. Having identified the significantly different cytokine profile associated with testis cancer, which cell type might be mainly responsible for its establishment? For addressing this question, an in vitro model was developed to assess the interactions and single contributions of immune and testicular cancer cells to the tumor environment in more detail. TCam2 cells (human seminoma-derived cell line) were co-cultured with human peripheral blood mononuclear cells (PBMCs) to interrogate responses to their co-localization. Data from nine independent experiments using PBMCs from eight different donors indicate that seminoma cell growth is unaffected by direct or indirect contact with PBMCs, at least in short-term. However, cytokine expression profiles of cell-to-cell co-cultured TCam2 cells show significantly increased mRNA levels of pro-inflammatory cytokines IL-1beta, IFN-gamma, TNF-alpha, TGF-beta1 and CCL-5 compared to mono-cultured controls. These outcomes resemble the ex vivo data and highlight the potential of neoplastic human germ cells to promote immune cell infiltration and to actively shape their cytokine microenvironment. Furthermore, three co-culture setups wi

Human testicular germ cell tumours commonly feature abundant infiltrating immune cells, most previously identified as T cells and macrophages. But what consequences come along with these changes within the tumour environment? In our study, in addition to immune-morphological analysis, the cytokine microenvironment of testicular cancers has been surveyed for the first time, performing RT-qPCR on human testicular biopsy samples. The results reveal significantly increased expression of pro-inflammatory cytokines in cancer samples relative to healthy tissue, as well as cytokines associated with B cells, whose presence can further be confirmed by immunohistochemistry. These ex vivo results suggest an exceptional involvement of B cells and pro-inflammatory cytokines in the immunopathology of testicular cancer. Having identified the significantly different cytokine profile associated with testis cancer, which cell type might be mainly responsible for its establishment? For addressing this question, an in vitro model was developed to assess the interactions and single contributions of immune and testicular cancer cells to the tumor environment in more detail. TCam2 cells (human seminoma-derived cell line) were co-cultured with human peripheral blood mononuclear cells (PBMCs) to interrogate responses to their co-localization. Data from nine independent experiments using PBMCs from eight different donors indicate that seminoma cell growth is unaffected by direct or indirect contact with PBMCs, at least in short-term. However, cytokine expression profiles of cell-to-cell co-cultured TCam2 cells show significantly increased mRNA levels of pro-inflammatory cytokines IL-1beta, IFN-gamma, TNF-alpha, TGF-beta1 and CCL-5 compared to mono-cultured controls. These outcomes resemble the ex vivo data and highlight the potential of neoplastic human germ cells to promote immune cell infiltration and to actively shape their cytokine microenvironment. Furthermore, three co-culture setups wi

According to WHO estimates, Neisseria gonorrhoeae accounted for 106 million infections in 2008, a number of cases approximately matching those of Chlamydia infections. Gonococcal infections thus represent one of the most common causes of sexually transmitted diseases worldwide, second only to trichomonas vaginalis infections.This guideline aims to improve patient care by optimizing the diagnosis and treatment of infections due to Neisseria gonorrhoeae and to raise awareness among medical professionals of current treatment options., Infektionen mit Neisseria gonorrhoeae sind nach globalen Schätzungen der WHO mit 106 Mio. Fällen in 2008 etwa gleich häufig wie Chlamydien-Infektionen und gehören damit nach Trichomonas vaginalis-Infektionen zu den häufigsten sexuell übertragenen Infektionen (STI) in der Welt.Ziele der Leitlinie ist die Verbesserung der Versorgung der Patienten durch Optimierung von Diagnostik und Therapie bei Infektionen mit Neisseria gonorrhoeae sowie die Verbesserung der Kenntnisse von Ärztinnen und Ärzte über aktuelle Therapieoptionen.

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