Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic neurons, appearance of Lewy bodies and presence of neuroinflammation. No treatments currently exist to prevent PD or delay its progression, and dopaminergic substitution treatments just relieve the consequences of dopaminergic neuron loss. Increasing evidence points to peripheral T lymphocytes as key players in PD, and recently there has been growing interest into the specific role of T helper (Th) 17 lymphocytes. Th17 are a proinflammatory CD4+ T cell lineage named after interleukin (IL)-17, the main cytokine produced by these cells. Th17 are involved in immune-related disease such as psoriasis, rheumatoid arthritis and inflammatory bowel disease, and drugs targeting Th17/IL-17 are currently approved for clinical use in such disease. In the present paper, we first summarized current knowledge about contribution of the peripheral immune system in PD, as well as about the physiopharmacology of Th17 and IL-17 together with its therapeutic relevance. Thereafter, we systematically retrieved and evaluated published evidence about Th17 and IL-17 in PD, to help assessing Th17/IL-17-targeting drugs as potentially novel antiparkinson agents. Critical appraisal of the evidence did not allow to reach definite conclusions: both animal as well as clinical studies are limited, just a few provide mechanistic evidence and none of them investigates the eventual relationship between Th17/IL-17 and clinically relevant endpoints such as disease progression, disability scores, intensity of dopaminergic substitution treatment. Careful assessment of Th17 in PD is anyway a priority, as Th17/IL-17-targeting therapeutics might represent a straightforward opportunity for the unmet needs of PD patients.

The recent interest in beta-blockers as possible agents for drug repurposing in oncology arises from many pre-clinical and epidemiologic studies suggesting a possible clinically relevant antitumour effect. In lung cancer, given the contradictory results obtained, it is crucial to further study its effects. A systematic review of the literature was planned to evaluate a possible beneficial effect of beta-blocker on overall survival in lung cancer patients. Medline and Embase databases were searched from inception until 1 May 2018 to identify published studies that assessed the effect beta-blocker use on overall survival in lung cancer patients. Risk of bias was evaluated by Newcastle-Ottawa scale. Hazard ratios and 95% confidence intervals for overall survival were estimated using a random-effects model. Of 920 studies, seven (all retrospective and observational, six cohort and one case-control), including 7448 patients, met the inclusion criteria. Beta-blocker users with lung cancer had no increased overall survival compared to non-users (hazard ratio = 1.00; 95% confidence interval = 0.91–1.10; I2 = 45%). Similarly, beta-blocker users with non-small cell lung cancer had no increased overall survival compared to beta-blocker non-users (hazard ratio = 0.96; 95% confidence interval = 0.80–1.17; I2 = 56%). Our findings do not suggest an overall survival advantage in patients with lung cancer using beta-blocker therapy when compared to non-users. Further prospective cohort studies, designed to overcome the intrinsic limitations of retrospective observational studies are warranted to definitively clarify any possible beneficial effect of beta-blockers on lung cancer overall survival.

No abstract