Macrophages are professional phagocytic cells that orchestrate innate immune responses and display remarkable phenotypic diversity at different anatomical locations. However, the mechanisms that control the heterogeneity of tissue macrophages are not well characterized. Here, we report that the nuclear receptor LXRα is essential for the differentiation of macrophages in the marginal zone (MZ) of the spleen. LXR deficient mice are defective in the generation of MZ and metallophilic macrophages, resulting in abnormal responses to blood-borne antigens. Myeloid specific expression of LXRα or adoptive transfer of wild-type monocytes rescues the MZ microenvironment in LXRα deficient mice. These results demonstrate that LXRα signaling in myeloid cells is crucial for the generation of splenic MZ macrophages and reveal an unprecedented role for a nuclear receptor in the generation of specialized macrophage subsets.

Age is one of the most important prognostic factors associated to lethality in SARS-CoV-2 infection. In multivariate analysis, advanced age was an independent risk factor for death. Recent studies suggest a role for the nucleotide-binding domain and leucine rich repeat containing family, pyrin domain containing 3 (NLRP3) inflammasome activation in lung inflammation and fibrosis in SARS-CoV and SARS-CoV-2 infections. Increased NLRP3/ apoptosis-associated speck-like protein (ASC) mRNA expression and increased caspase-1 activity, have been observed in aged lung, provoking increased and heightened expression levels of mature Interleukin (IL)-1β and IL-18 in aged individuals. Aged individuals have a basal predisposition to overreact to infection, displaying an increased hyper-inflammatory cascade, that seems not to be fully physiologically controlled. NLRP3 inflammasome is overactivated in aged individuals, through deficient mitochondrial functioning, increased mitochondrial Reactive Oxigen Species (mtROS) and/or mitochondrial (mt)DNA, leading to a hyper-response of classically activated macrophages and subsequent increases in IL-1 β. This NLRP3 over-activated status in elderly individuals, is also observed in telomere dysfunctional mice models. In our opinion, the NLRP3 inflammasome plays a central role in the increased lethality observed in elderly patients infected by COVID-19. Strategies blocking inflammasome would deserve to be studied.

Low-dose radiotherapy (LD-RT) has been used for several benign diseases, including arthrodegenerative and inflammatory pathologies. Despite its effectiveness in clinical practice, little is known about the mechanisms through which LD-RT modulates the various phases of the inflammatory response and about the optimal dose fractionation. The objective of this review is to deepen knowledge about the most effective LD-RT treatment schedule and radiobiological mechanisms underlying the anti-inflammatory effects of LD-RT in various in vitro experiments, in vivo studies, and clinical studies.

Background: Immune checkpoint inhibitors (ICI) have represented a revolution in the treatment of non-small-cell lung cancer (NSCLC). To improve these results, combined approaches are being tested. The addition of stereotactic ablative radiotherapy (SABR) to ICI seems promising. A systematic review was performed in order to assess the safety and efficacy of SABR-ICI combination. Material and Methods: MEDLINE databases from 2009 to March 3, 2019 were reviewed to obtain English language studies reporting clinical outcomes of the combination of ICI-SABR in NSCLC. 18 out of the 429 initial results fulfilled the inclusion criteria and were selected for review. Results: Eighteen articles, including six prospective studies, describing 1736 patients treated with an ICI-SABR combination fulfilled the selection criteria. The reported mean rates for local control and distant/abscopal response rates were 71% and 41%, respectively. Eleven studies reported progression-free survival and overall survival, with a mean of 4.6 and 12.4 months, respectively. Toxicity rates were consistent with the ones attributable to ICI treatment alone. Conclusions: The ICI-SABR combination has a good safety profile and achieves high rates of local control and greater chances of obtaining abscopal responses than SABR alone, with a relevant impact on PFS. More studies are needed to improve patient selection for an optimal benefit from this approach.

Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts prior to voting during a consensus conference. Setting: Online Delphi survey and consensus conference. Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management. Outcome measurements and statistical analysis: Statements were ranked by experts according to their level of agreement: 1-3 (disagree), 4-6 (equivocal), and 7-9 (agree). A priori (level 1) consensus was defined as 70% agreement and 15% disagreement, or vice versa. In the Delphi survey, a second analysis was restricted to stakeholder group(s) considered to have adequate expertise relating to each statement (to achieve level 2 consensus). Results and limitations: Overall, 116 statements were included in the Delphi survey. Of these statements, 33 (28%) achieved level 1 consensus and 49 (42%) achieved level 1 or 2 consensus. At the consensus conference, 22 of 27 (81%) statements achieved consensus. These consensus statements provide further guidance across a broad range of topics, including the management of variant histologies, the role/limitations of prognostic biomarkers in clinical decision making, bladder preservation strategies, modern radiotherapy techniques, the management of oligometastatic disease, and the evolving role of checkpoint inhibitor therapy in metastatic disease. Conclusions: These consensus statements provide further guidance on controversial topics in advanced and variant bladder cancer management until a time when further evidence is available to guide our approach. Patient summary: This report summarises findings from an international, multistakeholder project organised by the EAU and ESMO. In this project, a steering committee identified areas of bladder cancer management where there is currently no good-quality evidence to guide treatment decisions. From this, they developed a series of proposed statements, 71 of which achieved consensus by a large group of experts in the field of bladder cancer. It is anticipated that these statements will provide further guidance to health care professionals and could help improve patient outcomes until a time when good-quality evidence is available.

These consensus statements were developed by the European Association of Urology (EAU) and the European Society for Medical Oncology (ESMO) and are published simultaneously in European Urology and Annals of Oncology. Background: Although guidelines exist for advanced and variant bladder cancer management, evidence is limited/conflicting in some areas and the optimal approach remains controversial. Objective: To bring together a large multidisciplinary group of experts to develop consensus statements on controversial topics in bladder cancer management. Design: A steering committee compiled proposed statements regarding advanced and variant bladder cancer management which were assessed by 113 experts in a Delphi survey. Statements not reaching consensus were reviewed; those prioritised were revised by a panel of 45 experts before voting during a consensus conference. Setting: Online Delphi survey and consensus conference. Participants: The European Association of Urology (EAU), the European Society for Medical Oncology (ESMO), experts in bladder cancer management.

The COVID-19 pandemia is affecting people worldwide. Most of the patients suffered of a respiratory disease that will progress to an acute respiratory distress syndrome (ARDS). SARS-CoV-2 pneumonia severely ill patients, develop a systemic inflammatory response with a Cytokine Release Syndrome (CRS), that is characterized by a sudden increase in several pro-inflammatory cytokines, mainly IL-1, IL-6 and TNF-alfa by activated macrophages (M1 phenotype). Blocking IL-6 with tocilizumab and using respirator equipment seems to be a very important issue in this (SARS-CoV-2) pneumonia, but not all patients are referred to such treatments.Low dose radiotherapy (0,5 Gy), is an evidence-based anti-inflammatory treatment, that could modify the immune landscape in the lung affected of SARS-CoV-2 pneumonia, through macrophages polarization to alternatively activated Macrophages (M2 phenotype). Radiation-induced cancer risk could be assumed due to the very low dose used, the advanced age of the patients and the life-threatening condition of SARS-Cov2 pneumonia.LDRT is a cost-effective non-toxic treatment already available in most general hospitals. This fact allows that it would be used for the large number of patients that will suffer this disease, and that would not receive specific anti-IL-6 treatments in ICUs in low and middle income countries.

Purpose-Microsatellite instability (MSI) is the hallmark of cancer with DNA mismatch repair (MMR) deficiency and underlies 20-30% of endometrial cancer. Some in vitro studies suggest that radiation effects are modulated by the MMR system, however, little is known about the relationship between MSI and radiation response. The aim of this study was to elucidate whether MSI predicts clinical outcome in radiation treated endometrioid endometrial cancer (EEC).Methods-We have studied a consecutive series of 93 patients with EEC treated with extrafacial hysterectomy and postoperative radiotherapy. The median clinical follow up of patients was of 138 months, with a maximum of 232 months. Five quasimonomorphic mononucleotide markers (BAT-25, BAT-26, NR21, NR24 and NR27) were used for MSI classification.Results-Twenty five patients (22%) were classified as MSI. Either in the whole series and in early stages (I and II), univariate analysis showed a significant association between MSI and a poorer 10-years local disease free (LDFS), disease free (DFS), and cancer-specific survival (CSS). In multivariate analysis, MSI was excluded from de final regression model in the whole series, but in early stages, MSI provided additional significant predictive information independent of traditional prognostic and predictive factors (age, stage, grade and vascular invasion) for DFS (HR, 3.25, 95%