No abstract

Immune activation within the tumor microenvironment is one promising approach to induce tumor regression. Certain viruses including oncolytic viruses such as the herpes simplex virus (HSV) and non-oncolytic viruses such as the lymphocytic choriomeningitis virus (LCMV) are potent tools to induce tumor-specific immune activation. However, not all tumor types respond to viro-and/or immunotherapy and mechanisms accounting for such differences remain to be defined. In our current investigation, we used the non-cytopathic LCMV in different human melanoma models and found that melanoma cell lines produced high levels of CCL5 in response to immunotherapy. In vivo, robust CCL5 production in LCMV infected Ma-Mel-86a tumor bearing mice led to recruitment of NK cells and fast tumor regression. Lack of NK cells or CCL5 abolished the anti-tumoral effects of immunotherapy. In conclusion, we identified CCL5 and NK cell-mediated cytotoxicity as new factors influencing melanoma regression during virotherapy.

Daily exposure to strong magnetic fields during pregnancy had no deleterious effect on offspring; however, a developmental retardation could be observed postnatally with regard to weight gain and eye opening.

IntroductionUnderstanding prognosis – especially long-term outcome – in advanced non-small-cell lung cancer(NSCLC) is crucial to inform patients, guide treatment and plan supportive and palliative care.MethodsPrognostic factors influencing overall (OS) and progression-free survival (PFS) in 2082 patients with Wild-type(WT)-NSCLC (629 M1a, 249 M1b, 1204 M1c) are reported. Patients were included in the prospective German CRISP-registry recruiting in over 150 centers. Analysis for pretherapeutic factors was based on results from Cox proportional hazard models.ResultsCurrent M-descriptors of UICC-8 staging system were validated: M1a and M1b patients had significantly longer time to events compared to M1c (OS/PFS, medians 16.4/7.2; 17.8/6.7; 10.9/5.4 months). OS and PFS were influenced by number and location of metastatic organ systems. M1c and ≥4 metastatic organs involved had shorter OS and PFS than M1c with 1 to 3 organs (OS HR 1.69, p<001; PFS HR 1.81, p<001). M1b-liver metastases had shorter OS/PFS than M1b-involving other organs (OS HR 2.70, p=006; PFS HR 2.48, p=007). Based on number of involved organs(orgsys) and liver metastases, two risk groups (Low-risk: M1a, M1b-non-liver, M1c-1-3-orgsys-non-liver; High-risk: M1c-liver, M1b-liver, M1c-4+-orgsys) with significantly different prognosis could be amalgamated (OS/PFS, medians 14.3/6.5; 7.7/4.1 months). Other favourable factors were female gender and ECOG 0 with age showing no impact. T1- or N0-status were associated with longer OS than T2-4 or N2-3.ConclusionIn this large observational dataset, we further defined factors for outcome in WT-NSCLC - including increased number of involved metastatic organ systems and liver metastases - as those with overall poorer prognosis and reduced survival chance.

SummaryBackground: 2-4% of newly diagnosed cases of malignant disease involve cancer of unknown primary (CUP). This mixed entity is one of the 6 most common types of malignant disease in Germany. Highly refined treatment strategies can now be offered to patients with CUP.