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Urbanization is a global phenomenon that involves the transformation of natural areas into urban spaces, thereby subjecting organisms to new selective pressures including a wide variety of pollutants and changes in intra- and interspecific interactions. Considering that projections indicate that by the year 2050, 65% of the human population will live in urban areas and that urbanization is a phenomenon with an upward pattern, identifying these phenotypic traits is vital to implementing conservation and management plans for urban fauna. The urban environment may exert different selective pressures on sexually selected traits than more pristine environments, a phenomenon which has been well studied in birds but is less understood in other vertebrates such as lizards, although they are common inhabitants of urban environments. Here, we compare sexual coloration, parasite load, and immune response in Sceloporus torquatus lizards in urban and non-urban environments of Central Mexico. Our study shows that sexual coloration is more saturated (bluer) in male lizards from urban environments, while UV chroma was higher in non-urban lizards. The average parasite load is lower in urban lizards than in non-urban lizards, and we found a negative relationship between hemoparasite count and sexual coloration in male lizards from non-urban environments but not in male lizards from urban environments. Additionally, non-urban lizards exhibited a higher immune response. In female lizards, sexual coloration differed significantly between urban and non-urban environments, but parasite load and immune response did not differ. These results may be useful to improve herpetofauna conservation plans in urbanized environments.

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Toxoplasma gondii, the causative agent of toxoplasmosis, is widely distributed. This protozoan parasite is one of the best adapted, being able to infect innumerous species of animals and different types of cells. This chapter reviews current literature on extracellular vesicles secreted by T. gondii and by its hosts. The topics describe the life cycle and transmission (1); toxoplasmosis epidemiology (2); laboratorial diagnosis approach (3); The T. gondii interaction with extracellular vesicles and miRNAs (4); and the perspectives on T. gondii infection. Each topic emphases the host immune responses to the parasite antigens and the interaction with the extracellular vesicles and miRNAs.

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Vesículas Extracelulares , Interacciones Huésped-Parásitos , Toxoplasma , Toxoplasmosis , Vesículas Extracelulares/metabolismo , Toxoplasma/metabolismo , Humanos , Animales , Toxoplasmosis/metabolismo , Toxoplasmosis/parasitología , Toxoplasmosis/inmunología , MicroARNs/metabolismo , MicroARNs/genética

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Background and aim: Deficiency of zinc and selenium is common in persons living with human immunodeficiency virus (PLWHIV) and has been associated with the development of non-AIDS related comorbidities, impaired immune system function and mortality. Micronutrient supplementation on long-term-treated PLWHIV could bring potential clinical and immunological benefits improving their health status and quality of life. The aim of the present study is to analyze the effect of zinc and selenium supplementation on body composition, bone mineral density, CD4+ T-cell counts, metabolic profile and immune system status on clinical stable PLWHIV on long-term antiretroviral therapy (ART). Methods: This is a randomized pilot clinical trial in which we recruited 60 PLWHIV on ART who were assigned to the intervention groups: zinc (30 mg of zinc gluconate), selenium (200 µg of selenium yeast), zinc + selenium (same doses and presentations) or to a control group (without nutritional supplementation) who received supplementation during 6 months. Primary outcome was defined as changes in body composition (weight, muscle and fat mass and bone mineral density) and secondary outcomes as changes in biochemical and immunological parameters (CD4+ T-cell count, cholesterol, glucose, triglycerides and seric zinc and selenium seric concentrations) before and after supplementation. Peripheral blood mononuclear cells (PBMCs) of one individual of each intervention group were analyzed for single cell transcriptomics before and after supplementation. Results: BMI (p = 0.03), fat mass (p = 0.03), and trunk fat (p = 0.01) decreased after 6 months of selenium supplementation. No changes were observed for cholesterol, glucose or triglycerides after supplementation (p > 0.05 in all cases). CD4+ T cells percentage increased after 6 months of selenium supplementation (p = 0.03). On the transcriptome analysis, zinc and selenium supplementation induced changes on de expression of genes associated with the function of naive and memory CD8+ T-cells (p < 0.05 in all cases). Conclusion: Zinc and selenium supplementation could represent a complementary intervention that may improve the health status and immune response of treated PLWHIV.

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Antibodies are an essential component of the antiviral response in many species, but to date, there is no compelling evidence that bats are capable of eliciting a robust humoral immunity, including neutralizing antibodies. Here, we report that infection of Jamaican fruit bats with the bat influenza A virus H18N11 elicits a rapid and stable humoral immune response with a strong neutralizing capacity, associated with no detectable viral shedding after repeat challenge infection. Thus, the neutralizing antibody response of bats might play an important role in the bat immunity.

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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Quirópteros , Infecciones por Orthomyxoviridae , Quirópteros/virología , Quirópteros/inmunología , Animales , Anticuerpos Neutralizantes/inmunología , Infecciones por Orthomyxoviridae/inmunología , Infecciones por Orthomyxoviridae/virología , Infecciones por Orthomyxoviridae/veterinaria , Anticuerpos Antivirales/inmunología , Virus de la Influenza A/inmunología , Esparcimiento de Virus/inmunología

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INTRODUCTION: Tumors can be targeted by modulating the immune response of the patient. Programmed cell death protein 1 (PD-1) and programmed cell death ligand 1 (PD-L1) are critical immune checkpoints in cancer biology. The efficacy of certain cancer immunotherapies has been achieved by targeting these molecules using monoclonal antibodies. METHOD: Small-molecule drugs have also been developed as inhibitors of the PD-1/PD-L1 axis, with a mechanism of action that is distinct from that of antibodies: they induce the formation of PD-L1 homodimers, causing their stabilization, internalization, and subsequent degradation. Drug repurposing is a strategy in which new uses are sought after for approved drugs, expediting their clinical translation based on updated findings. In this study, we generated a pharmacophore model that was based on reported small molecules that targeted PD-L1 and used it to identify potential PD-L1 inhibitors among FDA-approved drugs. RESULTS: We identified 12 pharmacophore-matching compounds, but only 4 reproduced the binding mode of the reference inhibitors in docking experiments. Further characterization by molecular dynamics showed that pranlukast, an antagonist of leukotriene receptors that is used to treat asthma, generated stable and energyfavorable interactions with PD-L1 homodimers and induced homodimerization of recombinant PD-L1. CONCLUSION: Our results suggest that pranlukast inhibits the PD-1/PD-L1 axis, meriting its repurposing as an antitumor drug.

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BACKGROUND: The metabolic environment of glioma is extremely complex. Pyrimidine metabolism can significantly influence malignant progression of multiple kinds of cancer cells. In this study, we intend to explore the relationship between pyrimidine metabolism and malignant progression of glioma. METHODS: We analyzed two glioma RNA-sequencing databases to construct a pyrimidine metabolism-related risk signature. An individualized prognosis prediction model based on this risk signature was established. Functional analysis and in vitro experiments were conducted to assess the role of pyrimidine metabolism in the tumor-immune microenvironment and malignant progress of gliomas. RESULTS: The high-risk group, as predicted by the pyrimidine metabolism-related risk score, showed a tendency toward more malignant entities and poorer survival outcomes. Functional analysis revealed that pyrimidine metabolism significantly regulates the tumor-immune microenvironment. In vitro experiments confirmed that targeting pyrimidine metabolism-related genes can inhibit malignancy of glioma cell. CONCLUSION: In short, the pyrimidine metabolism-related signature we established could serve as an independent prognostic biomarker in diffuse gliomas and has a close association with regulation of the tumor-immune microenvironment.

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Non-muscle-invasive bladder cancer (NMIBC) presents management challenges due to its high recurrence rate and a complex tumor microenvironment (TME). This study investigated the effects of OncoTherad® (MRB-CFI1) nanoimmunotherapy on the TME of BCG-unresponsive NMIBC, focusing on alterations in monoamine oxidases (MAO-A and MAO-B) and immune markers: CD163, FOXP3, CD8, and CX3CR1. A comparative analysis of immunoreactivities was made before and after OncoTherad® treatment and an immune score (IS) was established to evaluate the correlation between immunological changes and clinical outcomes. Forty bladder biopsies of twenty patients were divided into 2 groups (n = 20/group): 1 (pre-treatment biopsies); and 2 (post-treatment biopsies). Our results showed stable MAO-A levels but a significant (p < 0.05) decrease in MAO-B immunoreactivity after treatment, suggesting OncoTherad®'s efficacy in targeting the tumor-promoting and immunosuppressive functions of MAO-B. Significant (p < 0.05) reductions in CD163 and FOXP3 immunoreactivities were seen in post-treatment biopsies, indicating a decreased presence of M2 macrophages and Tregs. Corroborating with these results, we observed reductions in tumor histological grading, focality and size, factors that collectively enhanced recurrence-free survival (RFS) and pathological complete response (PCR). Moreover, elevated IFN-γ immunoreactivities in treated biopsies correlated with increased counts of CD8+ T cells and higher CX3CR1 expression, underscoring OncoTherad®'s enhancement of cytotoxic T cell functionality and overall antitumor immunity. The IS revealed improvements in immune responses post-treatment, with higher scores associated with better RFS and PCR outcomes. These findings validate OncoTherad®'s capability to modify the bladder cancer microenvironment favorably, promoting effective immune surveillance and response.

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Inmunoterapia , Linfocitos Infiltrantes de Tumor , Monoaminooxidasa , Microambiente Tumoral , Macrófagos Asociados a Tumores , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/inmunología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Microambiente Tumoral/inmunología , Microambiente Tumoral/efectos de los fármacos , Masculino , Femenino , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/metabolismo , Persona de Mediana Edad , Anciano , Inmunoterapia/métodos , Macrófagos Asociados a Tumores/inmunología , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/efectos de los fármacos , Monoaminooxidasa/metabolismo , Anciano de 80 o más Años , Neoplasias Vesicales sin Invasión Muscular

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BACKGROUND: Cancer treatment has become a significant health challenge, with notable changes in recent years due to increasing knowledge of cancer biology. The use of immune checkpoint inhibitors (ICIs) has shown promising results, but they can induce adverse events (AEs), resulting in serious consequences for patients. Pharmaceutical care aims to prevent, identify, and address issues related to medications, such as AEs. AIM: The objective of this scoping review was to assess the contribution of pharmacists to the intervention and care of cancer patients undergoing treatment with ICIs. METHODS: The PubMed, Scopus, Embase, and Web of Science databases were searched for studies on the treatment of cancer patients treated with ICIs in which pharmacists participated. No time frame or language restriction was applied. Article screening was performed independently by two authors, with any discrepancies resolved by a third author. The studies were analyzed and included in this review following the inclusion and exclusion criteria. RESULTS: Nine studies fulfilled the inclusion criteria. Pharmaceutical care encompasses a variety of interventions, including providing guidance to patients and to the multidisciplinary team, monitoring and managing AEs, conducting pharmaceutical consultations, and recommending over-the-counter medications and laboratory tests, among other actions. Pharmaceutical recommendations led to better outcomes regarding AEs. CONCLUSIONS: Pharmaceutical care has a positive impact on oncological immunotherapy with ICIs, contributing to both health institutions through cost reduction and, most importantly, patients by improving treatment outcomes and enhancing the quality of life.

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Pneumococcal surface protein A (PspA) is an important virulence factor in Streptococcus pneumoniae that binds to lactoferrin and protects the bacterium from the bactericidal action of lactoferricins-cationic peptides released upon lactoferrin proteolysis. The present study investigated if PspA can prevent killing by another cationic peptide, indolicidin. PspA-negative pneumococci were more sensitive to indolicidin-induced killing than bacteria expressing PspA, suggesting that PspA prevents the bactericidal action of indolicidin. Similarly, chemical removal of choline-binding proteins increased sensitivity to indolicidin. The absence of capsule and PspA had an additive effect on pneumococcal killing by the AMP. Furthermore, anti-PspA antibodies enhanced the bactericidal effect of indolicidin on pneumococci, while addition of soluble PspA fragments competitively inhibited indolicidin action. Previous in silico analysis suggests a possible interaction between PspA and indolicidin. Thus, we hypothesize that PspA acts by sequestering indolicidin and preventing it from reaching the bacterial membrane. A specific interaction between PspA and indolicidin was demonstrated by mass spectrometry, confirming that PspA can actively bind to the AMP. These results reinforce the vaccine potential of PspA and suggest a possible mechanism of innate immune evasion employed by pneumococci, which involves binding to cationic peptides and hindering their ability to damage the bacterial membranes.

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Proteínas Bacterianas , Streptococcus pneumoniae , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/metabolismo , Proteínas Bacterianas/metabolismo , Lactoferrina/farmacología , Lactoferrina/metabolismo , Péptidos Catiónicos Antimicrobianos/farmacología , Péptidos Catiónicos Antimicrobianos/metabolismo , Unión Proteica

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Head and neck cancers, including cancers of the mouth, throat, voice box, salivary glands, and nose, are a significant global health issue. Radiotherapy and surgery are commonly used treatments. However, due to treatment resistance and disease recurrence, new approaches such as immunotherapy are being explored. Immune checkpoint inhibitors (ICIs) have shown promise, but patient responses vary, necessitating predictive markers to guide appropriate treatment selection. This study investigates the potential of non-invasive biomarkers found in saliva, oral rinses, and tumor-derived exosomes to predict ICI response in head and neck cancer patients. The tumor microenvironment significantly impacts immunotherapy efficacy. Oral biomarkers can provide valuable information on composition, such as immune cell presence and checkpoint expression. Elevated tumor mutation load is also associated with heightened immunogenicity and ICI responsiveness. Furthermore, the oral microbiota may influence treatment outcomes. Current research aims to identify predictive salivary biomarkers. Initial studies indicate that tumor-derived exosomes and miRNAs present in saliva could identify immunosuppressive pathways and predict ICI response. While tissue-based markers like PD-L1 have limitations, combining multiple oral fluid biomarkers could create a robust panel to guide treatment decisions and advance personalized immunotherapy for head and neck cancer patients.

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BACKGROUND: SARS-CoV-2 infection has become a major international issue, not only from a medical point of view, but also social, economic and political. Most of the available information comes from the United States, Europe, and China, where the population and the socioeconomic status are very different from Latin American countries. This study evaluates the effect of regional socioeconomic characteristics on mortality due SARS-CoV-2 infection in patients with immune-mediated rheumatic diseases (IMRD) from Argentina, Mexico and Brazil. METHODS: Data from three national registries, SAR-COVID (Argentina), CMR-COVID (Mexico) and ReumaCoV-Brasil (Brazil), were combined. Adult IMRD patients with SARS-CoV-2 infection were recruited. National data for each province/state, including population density, number of physicians per inhabitant, income, unemployment, GINI index, Municipal Human Development Index (MHDI), stringency index, vaccination rate and most frequent viral strains per period were assessed as risk factors for mortality due to COVID-19. RESULTS: A total of 4744 patients were included, 2534 (53.4%) from SAR-COVID, 1166 (24.6%) from CMRCOVID and 1044 (22.0%) from ReumaCoV-Brasil. Mortality due to COVID-19 was 5.4%. In the multivariable analysis, higher number of physicians per 1000 inhabitants and being infected during the vaccination period of each country were associated with lower mortality. After adjustment for socioeconomic factors, there was no association with country of residence and mortality. CONCLUSION: These findings corroborate the complex interplay between socioeconomic factors, rheumatic disease activity, and regional disparities as determinants of death due to COVID-19 in Argentina, Brazil and Mexico. Thus, this research provides valuable insights for guiding public health policies and clinical practice in the ongoing fight against the COVID-19 pandemic.

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COVID-19 , Enfermedades Reumáticas , Factores Socioeconómicos , Humanos , COVID-19/mortalidad , COVID-19/epidemiología , Enfermedades Reumáticas/mortalidad , Brasil/epidemiología , México/epidemiología , Argentina/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Adulto , SARS-CoV-2 , Factores de Riesgo , Desempleo/estadística & datos numéricos , Anciano , Sistema de Registros , Densidad de Población

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Despite treatment advances through immunotherapies, including anti-PD-1/PD-L1 therapies, the overall prognosis of non-small cell lung cancer (NSCLC) patients remains poor, underscoring the need for novel approaches that offer long-term clinical benefit. This review examined the literature on the subject over the past 20 years to provide an update on the evolving landscape of dendritic cell-based immunotherapy to treat NSCLC, highlighting the crucial role of dendritic cells (DCs) in immune response initiation and regulation. These cells encompass heterogeneous subsets like cDC1s, cDC2s, and pDCs, capable of shaping antigen presentation and influencing T cell activation through the balance between the Th1, Th2, and Th17 profiles and the activation of regulatory T lymphocytes (Treg). The intricate interaction between DC subsets and the high density of intratumoral mature DCs shapes tumor-specific immune responses and impacts therapeutic outcomes. DC-based immunotherapy shows promise in overcoming immune resistance in NSCLC treatment. This article review provides an update on key clinical trial results, forming the basis for future studies to characterize the role of different types of DCs in situ and in combination with different therapies, including DC vaccines.

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Carcinoma de Pulmón de Células no Pequeñas , Células Dendríticas , Neoplasias Pulmonares , Humanos , Células Dendríticas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/inmunología , Animales , Inmunoterapia/métodos , Vacunas contra el Cáncer/inmunología , Vacunas contra el Cáncer/uso terapéutico

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Currently, therapy for early-stage human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) is based on the combination of trastuzumab and pertuzumab plus chemotherapy in a neoadjuvant regimen. The INMUNOHER study aimed to detect immunological markers in peripheral blood and their association with treatment response. Sixty-two HER2+ BC patients were recruited. Pre-treatment samples were obtained before the start of treatment, while post-treatment samples were obtained after completing therapy and before surgery and were analyzed by flow cytometry. The pathologic complete response (pCR) rate achieved was 82.3%. The expression of the NKp30, PD-1, and TIM-3 receptors was reduced in the Natural Killer (NK)-CD56dim subset of patients who did not achieve pCR. Following therapy, many changes were found in leukocytes, including alterations in T cell lymphocyte proportions. Also, the percentage of NK cells decreased, and several phenotypic changes were observed in this population. After treatment, IFN-γ production by NK cells against HER2+-cells with or without trastuzumab was significantly reduced. HER2-targeted therapy plus chemotherapy demonstrated high efficacy in most patients, reducing the statistical power for finding immunological markers. However, NK subset phenotypes correlated better with response groups, and numerous changes in the percentage of leukocytes and T and NK cells, as well as changes in the functionality of NK cells, were observed in most patients after treatment, encouraging further research into these immune populations.

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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de la Mama , Células Asesinas Naturales , Terapia Neoadyuvante , Receptor ErbB-2 , Trastuzumab , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/inmunología , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Trastuzumab/uso terapéutico , Trastuzumab/administración & dosificación , Femenino , Terapia Neoadyuvante/métodos , Receptor ErbB-2/metabolismo , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/administración & dosificación , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adulto , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Anciano

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The investigation of coffee leaves as a source of bioactive principles represents a relatively unexplored area of research. The study assesses the potential adverse effects of an aqueous acetone extract derived from Coffea arabica var. Oro Azteca leaves. The phenolic composition of the extract was identified and quantified by UPLC-MS/MS, and its acute and repeated-dose effects were evaluated in six-week-old CD-1 mice (n = 11 for acute evaluation and n = 20 female and n = 20 male for repeated-dose evaluation). The extract demonstrated no significant toxicity, maintaining consistent body weight and exhibiting a hepatoprotective effect by reducing ALT levels at a dose of 500 mg/kg. Some hyperactivity was observed at the highest doses, but overall, the extract enhanced the immune response and showed no histological alterations, except for mild inflammation in certain organs. The extract, which contains abundant quinic acid, chlorogenic acid, epicatechin, procyanidin B2, and mangiferin, has been deemed safe for consumption.

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BACKGROUND: The development of therapies and vaccines for various diseases often necessitates the analysis of cellular immunity. However, unlike other rodents, the limited availability of reagents for Syrian hamsters restricts immunological analysis, particularly in the determination of serum effector molecules such as cytokines. In this study, we aim to produce and characterize the cytokines IFN-γ, TGF-ß, IL-6, IL-10, and TNF-α from Syrian hamsters in recombinant form and to generate polyclonal antibodies against them in rats. METHODS AND RESULTS: Cytokine transcript sequences were cloned into expression vectors in E. coli. Recombinant proteins were produced, purified through affinity chromatography, and characterized by Western blot using an anti-6xHis monoclonal antibody. Rats were immunized with the recombinant proteins to generate polyclonal antibodies (pAbs). These pAbs were characterized by Western blot and titrated by indirect ELISA. The recombinant cytokines rTNF-α, rIL-10, rIFN-γ, rTGF-ß, and rIL-6 were produced and specifically recognized at their expected molecular weights of 22.3 kDa, 19.8 kDa, 18.9 kDa, 11.8 kDa, and 22.9 kDa. pAbs were produced and demonstrated the ability to specifically recognize their target proteins with titers of 409,600 (rIL-10), 204,800 (rTNF-α), 102,400 (rIL-10), 51,200 (rTGF-ß), and 25,600 (rIFN-É£). CONCLUSIONS: The reagents produced represent a starting point for developing immunoassays to detect hamster cytokines, facilitating the analysis of cellular immunity in this biomodel.

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Citocinas , Inmunidad Celular , Mesocricetus , Proteínas Recombinantes , Animales , Citocinas/metabolismo , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/genética , Cricetinae , Ratas , Anticuerpos/inmunología , Escherichia coli/genética , Escherichia coli/metabolismo

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It has been spotlighted that the Tumor Microenvironment (TME) is crucial for comprehending cancer progression and therapeutic resistance. Therefore, this comprehensive review elucidates the intricate architecture of the TME, which encompasses tumor cells, immune components, support cells, and a myriad of bioactive molecules. These constituents collectively foster dynamic interactions that underpin tumor growth, metastasis, and nuanced responses to anticancer therapies. Notably, the TME's role extends beyond mere physical support, serving as a critical mediator in cancer-cell evolution, immune modulation, and treatment outcomes. Innovations targeting the TME, including strategies focused on the vasculature, immune checkpoints, and T-cell therapies, have forged new pathways for clinical intervention. However, the heterogeneity and complexity of the TME present significant challenges, necessitating deeper exploration of its components and their interplay to enhance therapeutic efficacy. This review underscores the imperative for integrated research strategies that amalgamate insights from tumor biology, immunology, and systems biology. Such an approach aims to refine cancer treatments and improve patient prognoses by exploiting the TME's complexity.

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Introduction: There are no reports in LATAM related to longitudinal humoral and cellular response to adenovirus based COVID-19 vaccines in people with Multiple Sclerosis (pwMS) under different disease modifying therapies (DMTs) and neutralization of the Omicron and Wuhan variants of SARS-COV-2. Methods: IgG anti- SARS-COV-2 spike titer were measured in a cohort of 101 pwMS under fingolimod, dimethyl fumarate, cladribine and antiCD20, as well as 28 healthy controls (HC) were measured 6 weeks after vaccination with 2nd dose (Sputnik V or AZD1222) and 3nd dose (homologous or heterologous schedule). Neutralizing capacity was against Omicron (BA.1) and Wuhan (D614G) variants and pseudotyped particles and Cellular response were analyzed. Results: Multivariate regression analysis showed anti-cd20 (ß= -,349, 95% CI: -3655.6 - -369.01, p=0.017) and fingolimod (ß=-,399, 95% CI: -3363.8 - -250.9, p=0.023) treatments as an independent factor associated with low antibody response (r2 adjusted=0.157). After the 2nd dose we found a correlation between total and neutralizing titers against D614G (rho=0.6; p<0.001; slope 0.8, 95%CI:0.4-1.3), with no differences between DMTs. Neutralization capacity was lower for BA.1 (slope 0.3, 95%CI:0.1-0.4). After the 3rd dose, neutralization of BA.1 improved (slope: 0.9 95%CI:0.6-1.2), without differences between DMTs. A fraction of pwMS generated anti-Spike CD4+ and CD8+ T cell response. In contrast, pwMS under antiCD20 generated CD8+TNF+IL2+ response without differences with HC, even in the absence of humoral response. The 3rd dose significantly increased the neutralization against the Omicron, as observed in the immunocompetent population. Discussion: Findings regarding humoral and cellular response are consistent with previous reports.

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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , Inmunosupresores , Esclerosis Múltiple , SARS-CoV-2 , Humanos , Masculino , Femenino , Inmunosupresores/uso terapéutico , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , SARS-CoV-2/inmunología , Persona de Mediana Edad , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/tratamiento farmacológico , COVID-19/inmunología , COVID-19/prevención & control , Adulto , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/sangre , Argentina , Adenoviridae/genética , Adenoviridae/inmunología , Inmunidad Humoral , Glicoproteína de la Espiga del Coronavirus/inmunología

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BACKGROUND: High-grade gliomas (HGG) are the most aggressive primary brain tumors with poor prognoses despite conventional treatments. Immunotherapy has emerged as a promising avenue due to its potential to elicit a targeted immune response against tumor cells. OBJECTIVE: This meta-analysis aimed to evaluate the efficacy and safety of various immunotherapeutic strategies, including immune checkpoint inhibitors (ICI), virotherapy, and dendritic cell vaccines (DCV) in treating HGG. METHODS: Following the PRISMA framework, we searched PubMed, Cochrane, and Embase for studies reporting outcomes of HGG patients treated with immunotherapy. Key metrics included overall survival, progression-free survival, and treatment-related adverse events. RESULTS: We reviewed 47 studies, analyzing data from 3674 HGG patients treated with immunotherapy. The mean overall survival for patients treated with ICI was 11.05 months, with virotherapy at 11.79 months and notably longer for DCV at 24.11 months. The mean progression-free survival (PFS) for ICIs was 3.65 months. Virotherapy demonstrated a PFS favoring the control group, indicating minimal impact, while DCV showed substantial PFS improvement with a median of 0.43 times lower hazard compared to controls (95% CI: 29-64%). Adverse events were primarily Grade 1 or 2 for ICI, included a Grade 5 event for virotherapy, and were predominantly Grade 1 or 2 for DCV, indicating a favorable safety profile. CONCLUSION: Immunotherapy holds potential as an effective treatment for HGG, especially DCV. However, results vary significantly with the type of therapy and individual patient profiles. Further randomized controlled trials are necessary to establish robust clinical guidelines and optimize treatment protocols.

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PURPOSE: This study aims to identify patient subgroups who benefit more from perioperative immunotherapy combined with chemotherapy (IO-CT) based on clinical and molecular characteristics in resectable non-small cell lung cancer (NSCLC). METHODS: Randomized controlled trials (RCTs) on perioperative IO-CT were searched. Beneficial differences of IO-CT regimens across different patient subgroups were assessed by pooling trial-specific ratios in event-free survival (EFS), overall survival (OS), pathological complete response (pCR), and major pathological response (MPR). RESULTS: Six studies (n = 3003) involving five IO-CT regimens were included. Compared to CT alone, all IO-CT regimens significantly improved EFS, OS, MPR, and pCR, but increased toxicity. Toripa-chemo showed the best EFS and nivo-chemo showed the best OS. Patients with PD-L1 ≥ 1% had more EFS benefits compared to those with PD-L1 < 1% (HR [hazard ratio]: 1.55, 95% CI 1.17-2.04). Squamous NSCLC patients had significantly more pCR and MPR benefits than non-squamous NSCLC patients (pCR: OR [odds ratio] 0.68, 95% CI 0.49-0.95; MPR: OR 0.61, 95% CI 0.45-0.82). Former smokers had significantly higher pCR benefits than non-smokers (OR: 2.18; 95% CI 1.21-3.92). Additionally, OS benefit was significantly higher in patients < 65 years compared to those ≥ 65 years (HR ratio: 0.59, 95% CI 0.36-0.95). For MPR, males benefited significantly more from IO-CT compared to females (OR: 1.69, 95% CI 1.18-2.42). CONCLUSION: Perioperative IO-CT is more effective but more toxic than CT alone in resectable NSCLC. Patients with PD-L1 ≥ 1%, squamous NSCLC, a history of smoking, age < 65 years and male gender may experience greater benefits from perioperative IO-CT.

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BACKGROUND: Globally, breast cancer is the most common type of malignant tumor. It has been demonstrated that TMEM41A is abnormally expressed in a number of cancers and is linked to a dismal prognosis. TMEM41A's involvement in breast cancer remains unknown, though. METHODS: Data from databases such as TCGA were used in this study. Expression differences were compared using non-parametric tests. Cox regression analysis was employed, and analyses such as Nomogram were used to assess the significance of TMEM41A in predicting the prognosis of breast cancer. Lastly, it was looked into how immune cell infiltration in breast cancer is related to TMEM41A expression levels. RESULTS: The results suggest that TMEM41A is overexpressed in breast cancer and correlates with poor prognosis (P = 0.01), particularly in early-stage and ductal A breast cancer (P < 0.01). Breast cancer patients' expression of TMEM41A was found to be an independent risk factor (HR = 1.132, 95% CI 1.036-1.237) by multifactorial Cox regression analysis. The Nomogram prediction model's c-index was 0.736 (95% CI 0.684-0.787). The results of GSEA biofunctional enrichment analysis included the B cell receptor signaling pathway (P < 0.05). Ultimately, there was a significant correlation (P < 0.05) between TMEM41A expression in breast cancer and an infiltration of twenty immune cells. CONCLUSIONS: Breast cancer tissues overexpress TMEM41A, which is linked to immune cell infiltration and prognosis (particularly in early stage and luminal A breast cancer). Overexpression of TMEM41A is anticipated to serve as a novel prognostic indicator and therapeutic target for breast cancer.