Several human polyomaviruses (HPyVs) were recently discovered. Merkel cell polyomavirus (MCPyV) induces Merkel cell carcinoma. HPyV6, HPyV7, and TSPyV have been associated with rare skin lesions in immunosuppressed patients. HPyV9, HPyV10, and Saint Louis Polyomavirus (STLPyV) have not been convincingly associated with any disease. The aim of this prospective study was to evaluate the cutaneous prevalence, persistence and viral load of HPyVs in healthy individuals. Eight hundred seventy forehead and hand swabs were collected from 109 volunteers 4–6 weeks apart (collection period-1). Fifty-nine participants were available for follow-up a decade later (collection period-2). HPyV-DNA prevalence and viral loads of MCPyV, HPyV6, HPyV7, TSPyV, HPyV9, HPyV10, and STLPyV were determined by virus-specific real-time PCRs. Risk factors for HPyV prevalence, short- and long-term persistence were explored by logistic regression analyses. Baseline prevalence rates were similar for forehead and hand: MCPyV 67.9/67.0%, HPyV6 31.2/25.7%, HPyV7 13.8/11.0%, HPyV10 11.9/15.6%, STLPyV 7.3/8.3%, TSPyV 0.9/0.9%, and HPyV9 0.9/0.9%. Short-term persistence in period-1 was found in 59.6% (MCPyV), 23.9% (HPyV6), 10.1% (HPyV7), 6.4% (HPyV10), 5.5% (STLPyV), and 0% (TSPyV and HPyV9) on the forehead, with similar values for the hand. Long-term persistence for 9–12 years occurred only for MCPyV (forehead/hand 39.0%/44.1% of volunteers), HPyV6 (16.9%/11.9%), and HPyV7 (3.4%/5.1%). Individuals with short-term persistence had significantly higher viral loads at baseline compared to those with transient DNA-positivity (p < 0.001 for MCPyV, HPyV6, HPyV7, and HPyV10, respectively). This was also true for median viral loads in period-1 of MCPyV, HPyV6, and HPyV7 of volunteers with long-term persistence. Multiplicity (two or more different HPyVs) was a risk factor for prevalence and persistence for most HPyVs. Further risk factors were older age for HPyV6 and male sex for MCPyV on the forehead. Smoking was not a risk factor. In contrast to MCPyV, HPyV6, HPyV7, and rarely STLPyV, polyomaviruses TSPyV, HPyV9, and HPyV10 do not seem to be long-term constituents of the human skin virome of healthy individuals. Furthermore, this study showed that higher viral loads are associated with both short- and long-term persistence of HPyVs on the skin. HPyV multiplicity is a risk factor for prevalence, short-term and/or long-term persistence of MCPyV, HPyV6, HPyV7, and HPyV10.

Cancer immunotherapy using antigen-specific CD8+ T cells depends on long-lasting anti-tumor function of the in vitro expanded T cells. T cell function is intricately linked to the activity of many metabolic pathways directly impacting the ability of CD8+ T cells to kill tumor cells. Metabolic conditioning in vitro better prepares CD8+ T cells for in vivo survival, tumor infiltration and tumor clearance. The mechanism underlying in vitro metabolic conditioning-induced augmented in vivo T cell function remains poorly understood. Here we show that metabolic conditioning of CD8+ effector T cells induces an oxidized cellular redox balance at least in part mediated by increased mitochondrial reactive oxygen species (ROS). This redox shift contributes to enhanced in vivo persistence and tumor clearance. In human tumour-infiltrating T cells, altering the redox balance ex-vivo reinvigorated pro-inflammatory cytokine production. Therefore, we believe that redox alterations present a targetable pathway to increase T cell-based anti-tumor immunotherapy efficacy.

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