The Flt3L/Flt3 Axis in Dendritic Cell Biology and Cancer Immunotherapy.

Dendritic cells (DCs) prime anti-tumor T cell responses in tumor-draining lymph nodes and can restimulate T effector responses in the tumor site. Thus, in addition to unleashing T cell effector activity, current immunotherapies should be directed to boost DC function. Herein, we review the potential function of Flt3L as a tool for cancer immunotherapy. Flt3L is a growth factor that acts in Flt3-expressing multipotent progenitors and common lymphoid progenitors. Despite the broad expression of Flt3 in the hematopoietic progenitors, the main effect of the Flt3/Flt3L axis, revealed by the characterization of mice deficient in these genes, is the generation of conventional DCs (cDCs) and plasmacytoid DCs (pDCs). However, Flt3 signaling through PI3K and mTOR may also affect the function of mature DCs. We recapitulate the use of Flt3L in preclinical studies either as a single agent or in combination with other cancer therapies. We also analyze the use of Flt3L in clinical trials. The strong correlation between type 1 cDC (cDC1) infiltration of human cancers with overall survival in many cancer types suggests the potential use of Flt3L to boost expansion of this DC subset. However, this may need the combination of Flt3L with other immunomodulatory agents to boost cancer immunotherapy.Work in the D.S. laboratory is funded by the CNIC; by the European Research Council (ERC-2016-Consolidator Grant 725091); by Agencia Estatal de Investigación (PID2019-108157RB); by Comunidad de Madrid (B2017/BMD-3733 Immunothercan-CM); by Fondo Solidario Juntos (BancoSantander); and by Fundació La Marató de TV3 (201723). The CNIC is supported by the Instituto deSalud Carlos III (ISCIII), the MICINN and the Pro CNIC Foundation.S

A Proposal for Nomenclature in Myeloid C-Type Lectin Receptors

Myeloid C-type lectin receptors (CLRs) comprise a family of receptors expressed by immune myeloid cells that share homologous C-type lectin domains. The implication of these CLRs in the regulation of homeostasis and activation of myeloid cells has generated a buoyant growth in the number of studies involving these receptors. Since their first description, diverse nomenclature has been used to refer to each of them, ranging from systematic classifications, such as gene name or cluster of differentiation, to non-systematic ones that include terminology based on gene expression patterns or function. In this review, we aim to summarize the different names used for the main myeloidCLRs and analyzewhich of themhave beenmore frequently used in the literature. In addition, we have examined the evolution of the terminology applied to these myeloid CLRs over time. Based on this analysis, we propose a consensus alias for each of those myeloid CLRs. However, we acknowledge that systematicity is required beyond this terminology based on use frequency. Therefore, we have included gene names as the standardization tool to gather the maximum agreement. We suggest that a standard nomenclature consisting of both gene names and consensus alias should be included at least in scientific abstracts, which would help to identify relevant literature, saving time and effort and fostering the research in this field in a more systematic manner.CF was supported by AECC Foundation (INVES192DELF). Work in the DS laboratory was funded by the CNIC and grant SAF2016-79040-R from Ministerio de Ciencia, Innovacion e Universidades (MCIU), Agencia Estatal de Investigacion and Fondo Europeo de Desarrollo Regional (FEDER); B2017/BMD-3733 Immunothercan-CM from Comunidad de Madrid; RD16/0015/0018-REEM from FIS-Instituto de Salud Carlos III, MICINN, and FEDER; Acteria Foundation; Constantes y Vitales prize (Atresmedia); La Marato de TV3 Foundation (201723); the European Research Council (ERC-2016-Consolidator Grant 725091); and the European Commission (635122-PROCROP H2020). The CNIC is supported by the MCIU and the Pro-CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Modeling systems from partial observations

Modeling systems from collected data faces two main difficulties: the first one concerns the choice of measurable variables that will define the learnt model features, which should be the ones concerned by the addressed physics, optimally neither more nor less than the essential ones. The second one is linked to accessibility to data since, generally, only limited parts of the system are accessible to perform measurements. This work revisits some aspects related to the observation, description, and modeling of systems that are only partially accessible and shows that a model can be defined when the loading in unresolved degrees of freedom remains unaltered in the different experiments

Self-inflicted wound with a nail in the heart: case report

Adequate diagnosis and treatment of penetrating cardiac injury (PCI) represents a great challenge for the surgeon in the emergency department (ED) because of its high mortality. It is estimated that more than 90% of mortality happens before the patient reaches the hospital and only 15---50% of those will receive appropriate medical treatment. Case report: A 42-year-old hemodynamically stable male is brought to the ED with a protruding nail in his thorax. He is taken to the operating room (OR) where a medial sternotomy is performed and an injury is found in the left ventricle. Cardiac muscle repair is performed with pericardial patch. Discussion: PCI from a suicide attempt secondary to a nail hammered into the chest is very rare and no previous reports were found by the author. Conclusion: The objects that penetrate cardiac structures must be removed in a proper OR with capable personnel and the resources available to perform procedures like an urgent thoracotomy or sternotomy

Brucelosis equina: estudio serológico en una tropilla con casos de mal de cruz

El Mal de Cruz es conocido como una forma de presentación de la brucelosis en los equinos. Consiste principalmente en una bursitis supurativa con abundante secreción y fistulización, con pus amarillento líquido, a veces complicada con sinovitis y artritis. Se localiza en la región topográfica de la cruz en los equinos (vértebras dorsales, especialmente 3ª, 4ª, 5ª, 6ª, 7ª, 8ª y 9ª torácica (bolsas supraespinosas y otras accesorias en la zona de la cruz). Como causales se ha citado a la Brucella abortus, a veces acompañada de Actinomyces bovis. El objetivo de este trabajo es comprobar la existencia de serología positiva a brucelosis en los animales con sintomatología de la enfermedad.Facultad de Ciencias Veterinaria

Brucelosis equina: estudio serológico en una tropilla con casos de mal de cruz

El Mal de Cruz es conocido como una forma de presentación de la brucelosis en los equinos. Consiste principalmente en una bursitis supurativa con abundante secreción y fistulización, con pus amarillento líquido, a veces complicada con sinovitis y artritis. Se localiza en la región topográfica de la cruz en los equinos (vértebras dorsales, especialmente 3ª, 4ª, 5ª, 6ª, 7ª, 8ª y 9ª torácica (bolsas supraespinosas y otras accesorias en la zona de la cruz). Como causales se ha citado a la Brucella abortus, a veces acompañada de Actinomyces bovis. El objetivo de este trabajo es comprobar la existencia de serología positiva a brucelosis en los animales con sintomatología de la enfermedad.Facultad de Ciencias Veterinaria

Brucelosis equina: estudio serológico en una tropilla con casos de mal de cruz

El Mal de Cruz es conocido como una forma de presentación de la brucelosis en los equinos. Consiste principalmente en una bursitis supurativa con abundante secreción y fistulización, con pus amarillento líquido, a veces complicada con sinovitis y artritis. Se localiza en la región topográfica de la cruz en los equinos (vértebras dorsales, especialmente 3ª, 4ª, 5ª, 6ª, 7ª, 8ª y 9ª torácica (bolsas supraespinosas y otras accesorias en la zona de la cruz). Como causales se ha citado a la Brucella abortus, a veces acompañada de Actinomyces bovis. El objetivo de este trabajo es comprobar la existencia de serología positiva a brucelosis en los animales con sintomatología de la enfermedad.Facultad de Ciencias Veterinaria

Contribución al conocimiento de la flora de Andalucía: citas novedosas e interesantes de la provincia de Almería

Contribution to the knowledge about Andalusian flora: new and interesting cites of the Almería province.Palabras clave. Corología, Isla de Alborán, sureste ibérico, xenófitas.Key words. Corology, Alborán Island, South-Eastern Iberian Peninsula, xenophytes

Enhanced anti-tumour immunity requires the interplay between resident and circulating memory CD8(+) T cells

The goal of successful anti-tumoural immunity is the development of long-term protective immunity to prevent relapse. Infiltration of tumours with CD8(+) T cells with a resident memory (Trm) phenotype correlates with improved survival. However, the interplay of circulating CD8(+) T cells and Trm cells remains poorly explored in tumour immunity. Using different vaccination strategies that fine-tune the generation of Trm cells or circulating memory T cells, here we show that, while both subsets are sufficient for anti-tumour immunity, the presence of Trm cells improves anti-tumour efficacy. Transferred central memory T cells (Tcm) generate Trm cells following viral infection or tumour challenge. Anti-PD-1 treatment promotes infiltration of transferred Tcm cells within tumours, improving anti-tumour immunity. Moreover, Batf3-dependent dendritic cells are essential for reactivation of circulating memory anti-tumour response. Our findings show the plasticity, collaboration and requirements for reactivation of memory CD8(+) T cells subsets needed for optimal tumour vaccination and immunotherapy.We are grateful to N. Anandasabapathy, J. Pardo and members of the D.S. lab for discussions and critical reading of the manuscript. We also thank R.A. Mota for the contribution to the development of animal models. We thank the CNIC facilities, personnel and to K. McCreath for editorial assistance. We are indebted to all the scientists who have shared reagents with us, as indicated in Methods. M.E. is the recipient of a CNIC International PhD Programme fellowship `La Caixa'-Severo Ochoa, 2013 Call (OSLC-CNIC-2013-04). S.I. is funded by grant SAF2015-74561-JIN. I. M. is supported by Asociacion Espanola contra el Cancer and Fundacion BBVA. A.H. is funded by the Spanish Ministry of Economy, Industry and Competitiveness (MEIC) and European Fund for Regional Development (FEDER) (SAF2015-65607-R). D.S. lab is funded by the MEIC and FEDER (SAF-2013-42920-R and SAF-2016-79040-R), and the Fondation ACTERIA. D.S. and I. M. lab are funded by the European Commission (635122-PRO-CROP H2020). D.S. and A.H. lab are funded by the CNIC. The CNIC is supported by the MEIC and the Pro CNIC Foundation, and is a Severo Ochoa Center of Excellence (SEV-2015-0505).S

Conventional type 1 dendritic cells protect against age-related adipose tissue dysfunction and obesity.

Conventional dendritic cells (cDCs) scan and integrate environmental cues in almost every tissue, including exogenous metabolic signals. While cDCs are critical in maintaining immune balance, their role in preserving energy homeostasis is unclear. Here, we showed that Batf3-deficient mice lacking conventional type 1 DCs (cDC1s) had increased body weight and adiposity during aging. This led to impaired energy expenditure and glucose tolerance, insulin resistance, dyslipidemia, and liver steatosis. cDC1 deficiency caused adipose tissue inflammation that was preceded by a paucity of NK1.1+ invariant NKT (iNKT) cells. Accordingly, among antigen-presenting cells, cDC1s exhibited notable induction of IFN-γ production by iNKT cells, which plays a metabolically protective role in lean adipose tissue. Flt3L treatment, which expands the dendritic cell (DC) compartment, mitigated diet-induced obesity and hyperlipidemia in a Batf3-dependent manner. This effect was partially mediated by NK1.1+ cells. These results reveal a new critical role for the cDC1-iNKT cell axis in the regulation of adipose tissue homeostasis.We are grateful to the Immunology, Ophthalmology, and ENT Department at the UCM for providing useful discussion and to Gillian Dunphy and Antonia Tomás for critically reading the manuscript. We thank the CNIC and UCM facilities. Funding: Work in the S.I. laboratory is funded by the Spanish Ministerio de Ciencia, Innovación (MICINN), Agencia Estatal de Investigación (AEI) and Fondo Europeo de Desarrollo Regional (FEDER), RTI2018-094484-BI00, and RYC-2016-19463. EHG is the recipient of an FPI fellowship (PRE2019-087509) from the Spanish Ministry of Science and Innovation. Work in the DS laboratory is funded by the CNIC; the European Research Council (ERC-2016-Consolidator Grant 725091); the MICINN, AEI and FEDER (PID2019-108157RB); Comunidad de Madrid (B2017/BMD-3733 Immunothercan-CM); Atresmedia (Constantes y Vitales prize); and Fundació La Marató de TV3 (201723). Work in the G.S. laboratory receives funding from the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement n° ERC 260464, EFSD/Lilly European Diabetes Research Programme GS, 2017 Leonardo Grant for Researchers and Cultural Creators, BBVA Foundation (Investigadores-BBVA-2017) IN[17]_BBM_BAS_0066, MINECO-FEDER SAF2016-79126-R, EUIN2017-85875, Comunidad de Madrid IMMUNOTHERCAN-CM S2010/BMD-2326 and B2017/BMD-3733 and Fundación AECC. IN receives funding from EFSD/Lilly (2019), EFSD Rising star (2019), and JdC— Incorporation (IJC2018-035390-I). The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the MICINN, and the Pro CNIC Foundation.S