Reprogramming the tumor microenvironment to increase immune-mediated responses is currently of intense interest. Patients with immune-infiltrated “hot” tumors demonstrate higher treatment response rates and improved survival. However, only the minority of tumors are hot, and a limited proportion of patients benefit from immunotherapies. Innovative approaches that make tumors hot can have immediate impact particularly if they repurpose drugs with additional cancer-unrelated benefits. The seasonal influenza vaccine is recommended for all persons over 6 mo without prohibitive contraindications, including most cancer patients. Here, we report that unadjuvanted seasonal influenza vaccination via intratumoral, but not intramuscular, injection converts “cold” tumors to hot, generates systemic CD8+ T cell-mediated antitumor immunity, and sensitizes resistant tumors to checkpoint blockade. Importantly, intratumoral vaccination also provides protection against subsequent active influenza virus lung infection. Surprisingly, a squalene-based adjuvanted vaccine maintains intratumoral regulatory B cells and fails to improve antitumor responses, even while protecting against active influenza virus lung infection. Adjuvant removal, B cell depletion, or IL-10 blockade recovers its antitumor effectiveness. Our findings propose that antipathogen vaccines may be utilized for both infection prevention and repurposing as a cancer immunotherapy.
Vitis vinifera L. varieties were spread through cuttings following historic migrations of people, trades, or after biological crises due to pests outbreaks. Some today’s varieties could be more than a 1000 years old and, although over the centuries these varieties generated most of the remaining cultivars, their origin could be impossible to track back. The Italian grapevine biodiversity is one of most important, most likely due to its strategic position in the middle of the Mediterranean sea. Unravelling of its structure is challenging because of its complexity and the lack of historical documentation. In this paper molecular data are compared with historical documentations. Simple Sequence Repeats fingerprinting are molecular markers best suited to investigate genetic relationships and identify pedigrees. South-Italian germplasm was studied with 54 nuclear microsatellites. A family was identified, consisting of two parents and three siblings and further genetically characterized with six nuclear and five chloroplast microsatellites and described with ampelographic and phylometric analysis. Although these latter were not informative for the kinship identification. The common Bombino bianco was the female parent and the previously unknown Uva rosa antica was the male parent. Bombino nero, Impigno and the popular Uva di Troia, all typical of the south-east Italy, were the offspring. Further research showed that the Uva rosa antica was a synonym of Quagliano and Bouteillan noir, both minor varieties. Quagliano was considered to be autochthonous of some alpine valleys in the north-west of Italy and Bouteillan noir is a neglected variety of Vancluse in France. This finding uncovers the intricate nature of Italian grape cultivars, considered peculiar of an area, but possibly being the remains of ancient latin founding varieties. Consequently, intriguing new hypotheses are discussed and some conclusions are drawn, based on the peculiar geographical origin of the parents, on the distribution of the offspring, on the chance of a single, and perhaps intentional, crossing event.
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