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Epithelial ovarian cancer (EOC) is one of the most lethal gynecological cancers worldwide. EOC cells educate tumor-associated macrophages (TAM) through CD44-mediated cholesterol depletion to generate an immunosuppressive tumor microenvironment (TME). In addition, tumor cells frequently activate Notch1 receptors on endothelial cells (EC) to facilitate metastasis. However, further work is required to establish whether the endothelium also influences the education of recruited monocytes. Here, we report that canonical Notch signaling through RBPJ in ECs is an important player in the education of TAMs and EOC progression. Deletion of Rbpj in the endothelium of adult mice reduced infiltration of monocyte-derived macrophages into the TME of EOC and prevented the acquisition of a typical TAM gene signature; this was associated with stronger cytotoxic activity of T cells and decreased tumor burden. Mechanistically, CXCL2 was identified as a novel Notch/RBPJ target gene that regulated the expression of CD44 on monocytes and subsequent cholesterol depletion of TAMs. Bioinformatic analysis of ovarian cancer patient data showed that increased CXCL2 expression is accompanied by higher expression of CD44 and TAM education. Together, these findings indicate that EOC cells induce the tumor endothelium to secrete CXCL2 in order to establish an immunosuppressive microenvironment.

[cat]El principal objectiu del present article consisteix en plantejar les possibles relacions entre Die Balearen i la historiografia mallorquina contemporània, per la via de mostrar com la informació que proporciona aquesta obra ha constituït i pot ser encara constitueix una excel·lent base documental per als estudis històrics, especialment per aquells que enfoquen la segona meitat del segle XIX; com també perquè de la descripció realitzada per Lluís Salvador es deriven alguns dels temes que resulten especialment interessants per a la historiografia mallorquina de l’època contemporània. A més, tant l’obra com el seu autor són mereixedors de formar part de la Història de Mallorca., [eng]The main aim of the present article points out to the possible relations between Die Balearen and the contemporary Majorcan historiography, by means to show how the information provided by this work has constituted and it still constitutes an excellent documentary base for the historical studies, especially for those that focus the second half of the 19th century. Besides, some of the most interesting subjects for the Majorcan modern historiography spring from the description of the Balearic Island done by Lluís Salvador; and also much of this work and the author himself do deserve to form part of the History of Majorca.

Aquest volum, escrit per l'eclesiàstic Joan Binimelis (1538/9-1616), constitueix la primera edició crítica del Llibre V de la Història general del Regne de Mallorca en la versió catalana que, com és sabut, és l'original. Sens dubte, aquesta part de l'obra, dedicada a la descripció geogràfica de Mallorca i de caràcter autònom respecte a la narració històrica i cronística, representa l'aportació més original de l'autor i la que manté més vigència i interès avui dia, tant per la modernitat del seu plantejament, com per la diversitat dels aspectes que són objecte de la seua metòdica atenció: situació geogràfica, afrontacions, proveïment d'aigua, cales i aptesa per a desembarcaments, cabuda i possibilitats d'ancoratge, demografia, dades econòmiques -produccions agrícoles i ramaderes--, dades històriques, règim jurídic, institucions, monuments i d'altres informacions rellevants de les poblacions illenques. This volume, written by the ecclesiastic Joan Binimelis (1538/9-1616), is the first critical edition of Book V of the Història general del Regne de Mallorca in the Catalan version which, as is well known, is the original. Undoubtedly, this part of the work, devoted to the geographical description of Mallorca and independent of the historical and chronological narrative, represents the author's most original contribution and the one that remains most relevant and interesting today, both for the modernity of its approach and for the diversity of the aspects that are the object of his methodical attention: geographical situation, boundaries, water supply, coves and suitability for landing, anchoring capacity and possibilities, demography, economic data - agricultural and livestock production -, historical data, legal system, institutions, monuments and other relevant information on the island populations.

Melanoma is an immunogenic tumor; however, the efficacy of immune-therapy shows large inter-individual variation with possible influence of background genetic variation. In this study we report the influence of genetic polymorphisms in the type I interferon gene cluster on chromosome 9p22 on melanoma survival. We genotyped 625 melanoma patients recruited in an oncology center in Germany for 44 polymorphisms located on chromosome 9p22 that were informative for 299 polymorphisms and spanned 15 type I interferon genes. Our results showed associations between time to metastasis/survival and two linked (r(2) = 0.76) polymorphisms, rs10964859 (C>G) and rs10964862 (C>A). The rs10964859 polymorphism was located at 3'UTR and rs10964862 was 9.40 Kb towards 5'UTR of IFNW1 gene. The carriers of the variant alleles of the rs10964859 and rs10964862 polymorphisms were associated with a reduced disease-free survival. The validation of data in an independent group of 710 patients from Spain showed that the direction of the effect was similar. Stratification based on therapy showed that the adverse effect on metastasis development was statistically significant in the patients from Spain who did not receive any treatment and were homozygous for variant allele of rs10964862 (HR = 2.52, 95% CI 1.07-5.90; P = 0.03). Patients homozygous for rs10964859 (HR = 2.01, 95% CI 1.17-3.44; P = 0.01) and rs10964862 (HR 1.84, 95% CI 1.03-3.27, P = 0.04) were associated to increased risk of death following metastasis. GTCGACAA haplotype, found in 8.8% of the patients, was associated with an increased risk of death (HR 1.94, 95% CI 1.16-3.26, P = 0.01). In conclusion, our results identified genetic variants in interferon genes that influence melanoma progression and survival with modulation of effect due to treatment status.

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