RESUMEN
A sensitive detection of carbohydrate antigen 15-3 (CA15-3) levels may allow for early diagnosis and monitoring the treatment of breast cancer, but this can only be made in routine clinical practice if low-cost immunosensors are available. In this work, we developed a sandwich-type electrochemical immunosensor capable of rapid detection of CA15-3 with an ultra-low limit of detection (LOD) of 0.08 fg mL-1 within a wide linear concentration range from 0.1 fg mL-1 to 1 µg mL-1. The immunosensor had a matrix of a layer-by-layer film of Au nanoparticles and reduced graphene oxide (Au-rGO) co-electrodeposited on screen-printed carbon electrodes (SPCE). The high sensitivity was achieved by using secondary antibodies (Ab2) labeled with horseradish peroxidase (HRP) in the presence of hydrogen peroxide (H2O2) as signal amplifiers, and hydroquinone (HQ) was used as an electron mediator. The immunosensor was selective for CA15-3 in human serum and artificial saliva samples, robust, and stable to permit storage at 4 °C for more than 30 days. With its high performance, the immunosensor may be incorporated into future point-of-care (POC) devices to determine CA15-3 in distinct biological fluids, including in blood and saliva samples.
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Biomarcadores de Tumor/sangre , Técnicas Electroquímicas/métodos , Grafito/química , Inmunoensayo/métodos , Nanopartículas del Metal/química , Mucina-1/sangre , Anticuerpos Inmovilizados/inmunología , Armoracia/enzimología , Biomarcadores de Tumor/inmunología , Oro/química , Peroxidasa de Rábano Silvestre/química , Humanos , Peróxido de Hidrógeno/química , Hidroquinonas/química , Límite de Detección , Mucina-1/inmunología , Reproducibilidad de los Resultados , Saliva/químicaRESUMEN
OBJECTIVE: To examine the prevalence and prognostic role of tumor microenvironment (TME) markers in uterine carcinosarcoma (UCS) through immunohistochemical characterization. METHODS: The internal database of our institution was queried out for women with UCS who underwent surgery and thereafter postoperative chemotherapy with carboplatin and paclitaxel between January 2012 and December 2017. Tissue microarrays containing surgical samples of UCS from 57 women were assessed by immunohistochemistry for CD3, CD4, CD8, FOXP3, PD-1, PD-L1, and PD-L2. RESULTS: The mean age was 65.3 years (range, 49 to 79 years). For the epithelial component (E), CD3_E and CD4_E were highly expressed in 38 (66.7%) and in 40 (70.1%) patients, respectively, and were significantly associated with more advanced stages (p = 0.038 and p = 0.025, respectively). CD8_E was highly expressed in 42 (73.7%) patients, FOXP3_E 16 (28.1%), PD-1_E 35 (61.4%), PD-L1_E 27 (47.4%) and PD-L2_E 39 (68.4%). For the sarcomatous component (S), the prevalence of high expression was: CD3_S 6 (10.5%), CD4_S 20 (35.1%), CD8_S 44 (77.2%), FOXP3_S 8 (14%), PD-1_S 14 (24.6%), PD-L1_S 14 (24.6%) and PD-L2_S 8 (14%). By multivariate analysis, the CD8/FOXP3_S ratio (p = 0.026), CD4_E (p = 0.010), PD-L1_E (p = 0.013) and PD-L1_S (p = 0.008) markers significantly influenced progression-free survival. CD4/FOXP3_S ratio (p = 0.043), PD-1_E (p = 0.011), PD-L1_E (p = 0.036) and PD-L1_S (p = 0.028) had a significant association with overall survival. CONCLUSION: Some differences in UCS clinical outcomes may be due to the subtype of TILs and PD-1/PD-L1 axis immune checkpoint signaling.
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Carcinosarcoma/inmunología , Carcinosarcoma/mortalidad , Linfocitos Infiltrantes de Tumor/metabolismo , Neoplasias Uterinas/inmunología , Neoplasias Uterinas/mortalidad , Anciano , Antineoplásicos/uso terapéutico , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/inmunología , Carboplatino/uso terapéutico , Carcinosarcoma/sangre , Femenino , Regulación Neoplásica de la Expresión Génica/inmunología , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Paclitaxel/uso terapéutico , Prevalencia , Pronóstico , Receptor de Muerte Celular Programada 1/metabolismo , Transducción de Señal/inmunología , Microambiente Tumoral/inmunología , Neoplasias Uterinas/sangreRESUMEN
Adrenocortical carcinoma (ACC) is a rare, but highly aggressive cancer of the adrenal cortex with a generally poor prognosis. Despite being rare, completely resected ACCs present a high risk of recurrence. Musashi-2 (MSI2) has recently been recognized as a potential prognostic biomarker and therapeutic target in many cancers. However, no studies have evaluated the clinical significance of MSI2 expression in ACC. Here, we addressed MSI2 expression and its association with ACC prognosis and clinicopathological parameters. MSI2 expression was analyzed in TCGA, GSE12368, GSE33371, and GSE49278 ACC datasets; and its correlation with other genes and immune cell infiltration were investigated by using the R2: Genomics Analysis and Visualization Platform and TIMER databases, respectively. Enrichment analysis was performed with the DAVID Functional Annotation Tool. Kaplan-Meier curves, log-rank tests, and Cox regression analyses were used to explore the prognostic role of MSI2 in ACC. Our findings demonstrated the potential value of MSI2 overexpression as an independent predictor of poor prognosis in patients with completely resected ACC (hazard ratio 6.715, 95% confidence interval 1.266 - 35.620, p =.025). In addition, MSI2 overexpression was associated with characteristics of unfavorable prognosis, such as cortisol excess (p = .002), recurrence (p =.003), and death (p =.015); positively correlated with genes related to steroid biosynthesis (p < .05); and negatively correlated with immune-related pathways (p < .05). Our findings demonstrate that MSI2 has value as a prognostic marker for completely resected ACC and reinforce the investigation of its role as a possible therapeutic target for patients with ACC.
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Neoplasias de la Corteza Suprarrenal , Carcinoma Corticosuprarrenal , Biomarcadores de Tumor/inmunología , Regulación Neoplásica de la Expresión Génica/inmunología , Proteínas de Neoplasias/inmunología , Proteínas de Unión al ARN/inmunología , Neoplasias de la Corteza Suprarrenal/inmunología , Neoplasias de la Corteza Suprarrenal/mortalidad , Carcinoma Corticosuprarrenal/inmunología , Carcinoma Corticosuprarrenal/mortalidad , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esteroides/inmunologíaRESUMEN
PURPOSE: Dendritic cells (DCs) are the most potent antigen-presenting cells that play a major role in initiating the antitumor immune response in different types of cancer. However, the prognostic significance of the accumulation of these cells in human early breast tumors is not totally clear. The aim of this study is to evaluate the prognostic relevance of CD1a( +) and CD83( +) dendritic cells in early breast cancer patients. METHODS: We conducted immunohistochemical assays to determine the number of stromal CD1a( +) and CD83( +) DCs in primary tumors from early invasive ductal breast cancer patients, and analyzed their association with clinico-pathological characteristics. RESULTS: Patients with high CD1a( +) DC number had lower risk of bone metastatic occurrence, as well as, longer disease-free survival (DFS), bone metastasis-free survival (BMFS) and overall survival (OS). Moreover, CD1a( +) DC number was an independent prognostic factor for BMFS and OS. In contrast, we found that patients with high number of CD83( +) DCs had lower risk of mix (bone and visceral)-metastatic occurrence. Likewise, these patients presented better prognosis with longer DFS, mix-MFS and OS. Furthermore, CD83( +) DC number was an independent prognostic factor for DFS and OS. CONCLUSION: The quantification of the stromal infiltration of DCs expressing CD1a or CD83 in early invasive breast cancer patients serves to indicate the prognostic risk of developing metastasis in a specific site.
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Antígenos CD1/análisis , Antígenos CD/análisis , Neoplasias de la Mama/patología , Inmunoglobulinas/análisis , Glicoproteínas de Membrana/análisis , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD/inmunología , Antígenos CD1/inmunología , Biomarcadores de Tumor/inmunología , Células Dendríticas/inmunología , Células Dendríticas/patología , Femenino , Humanos , Inmunoglobulinas/inmunología , Glicoproteínas de Membrana/inmunología , Persona de Mediana Edad , Estudios Retrospectivos , Análisis de Supervivencia , Antígeno CD83RESUMEN
BACKGROUND/AIM: Liver metastases are among the principal mortality causes in cancer patients. Dendritic cell immunotherapies have shown promising results in some tumors by mediating immunological mechanisms that could be involved in liver metastases during primary tumor growth. The present study aimed to evaluate the impact of prophylactic dendritic cell vaccination on the liver of mice with 4T1 mouse breast carcinoma. MATERIALS AND METHODS: Adult female Balb/c mice were submitted or not to vaccination with dendritic cells before the induction of 4T1 tumor lineage. Liver tissues from mice were analyzed by flow cytometry (markers CD3, CD4, CD8, CD25, IL-10, IL-12, IL-17, TNF-α, IFN-γ, T-bet, GATA3, RORγt, and FoxP3) and hematoxylin-eosin. The dendritic cell vaccine was differentiated and matured ex vivo from the bone marrow. RESULTS: Prophylactic vaccination reduced areas of liver metastases (p=0.0049), induced an increase in the percentage of total T and cytotoxic T lymphocytes (p<0.0001), as well as FoxP3+ (p<0.0001). It also increased the levels of cytokines IL-10 and IL-17 in helper T lymphocytes (p<0.0001). CONCLUSION: The prophylactic dendritic cell vaccine changed the cell phenotype in the immune response of liver, and it was able to reduce metastases. Cytotoxic T cells and regulatory T lymphocytes were more present, likewise, the production of IL-10 and IL-7 simultaneously, demonstrating that the vaccine can induce a state of control of pro-inflammatory responses, which can provide a less favorable environment for metastatic tumor growth.
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Neoplasias de la Mama/inmunología , Vacunas contra el Cáncer/inmunología , Células Dendríticas/inmunología , Neoplasias Hepáticas/inmunología , Hígado/inmunología , Animales , Biomarcadores de Tumor/inmunología , Médula Ósea/inmunología , Neoplasias de la Mama/patología , Modelos Animales de Enfermedad , Femenino , Inmunidad/inmunología , Inmunoterapia/métodos , Hígado/patología , Neoplasias Hepáticas/patología , Ratones , Ratones Endogámicos BALB C , Linfocitos T Citotóxicos/inmunología , Linfocitos T Reguladores/inmunología , Vacunación/métodosRESUMEN
BACKGROUND: For non-small cell lung cancer (NSCLC) the most used method for analysing programmed cell death ligand 1 (PD-L1) expression is the Tumor Proportion Score (TPS). Nevertheless, for other tumour types, the Combined Positive Score (CPS) has been the method of choice. AIM: Evaluate and compare the predictive value of both CPS and TPS as predictors of immunotherapy response in NSCLC, and to evaluate the agreement intra-observer between both methods and inter-observer between two expert lung pathologists. METHODS: 56 NSCLC patients who were treated with anti-programmed cell death 1 (PD-1)/PD-L1 therapy were included. Two pathologists evaluated all cases independently, considering the sample's adequacy for analysis, and the PD-L1 expression by TPS and CPS. RESULTS: The Kappa coefficient for adequacy was 0.82 (95% CI 0.67 to 0.97). There was a high agreement between TPS and CPS and a high agreement between pathologists concerning the two methods. The Kappa coefficient between TPS and CPS was 0.85 for both pathologists, and between pathologists was 0.94 and 0.93 for TPS and CPS, respectively. CONCLUSIONS: Both methods proved to be equally predictive of response to anti-PD-1/PD-L1 therapy. There was both a high intra-observer agreement between the two methods and a high inter-observer agreement between pathologists. This study suggests that CPS could also be used in a routine setting for immunotherapy decision in NSCLC.
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Antígeno B7-H1/análisis , Biomarcadores de Tumor/análisis , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Antígeno B7-H1/inmunología , Biomarcadores de Tumor/inmunología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/terapia , Femenino , Humanos , Inmunohistoquímica , Inmunoterapia , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios RetrospectivosRESUMEN
OBJECTIVE: Increasing evidence demonstrates that immune signature plays an important role in the prognosis of gastric cancer (GC). We aimed to develop and validate a robust immune-related gene pair (IRGP) signature for predicting the prognosis of GC patients. METHODS: RNA-Seq data and corresponding clinical information of GC cohort were downloaded from the TCGA (The Cancer Genome Atlas Program) data portal. GSE84437 and GSE15459 microarray datasets were included as independent external cohorts. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to build the best prognostic signature. All patients were classified into the high immune-risk and low immune-risk groups via the optimal cut-off of the signature scores determined by time-dependent receiver-operating characteristic (ROC) curve analysis. The prognostic role of the signature was measured by a log-rank test and a Cox proportional hazard regression model. RESULTS: 14 immune gene pairs consisting of 25 unique genes were identified to construct the immune prognostic signature. High immune-risk groups showed poor prognosis in the TCGA datasets and GSE84437 datasets as well as in the GSE15459 datasets (all P < 0.001). The 14-IRGP signature was an independent prognostic factor of GC after adjusting for other clinical factors (P < 0.05). Functional analysis revealed that DNA integrity checkpoint, DNA replication, T-cell receptor signaling pathway, and B-cell receptor signaling pathway were enriched in the low immune-risk groups. B cells naive and Monocytes were significantly higher in the high-risk group, and B-cell memory and T-cell CD4 memory activated were significantly higher in the low-risk group. The prognostic signature based on IRGP reflected infiltration by several types of immune cells. CONCLUSION: The novel proposed clinical-immune signature is a promising biomarker for prediction overall survival in patients with GC and providing new insights into the treatment strategies.
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Neoplasias Gástricas/genética , Neoplasias Gástricas/inmunología , Biomarcadores de Tumor/inmunología , Biomarcadores de Tumor/metabolismo , Replicación del ADN , Bases de Datos Genéticas , Bases de Datos de Ácidos Nucleicos , Conjuntos de Datos como Asunto , Expresión Génica , Humanos , Memoria Inmunológica , Linfocitos Infiltrantes de Tumor , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Receptores de Antígenos de Linfocitos B/metabolismo , Receptores de Antígenos de Linfocitos T/metabolismo , Análisis de Regresión , Neoplasias Gástricas/mortalidadRESUMEN
Immune checkpoint inhibitors (ICI) aim to restore the immune system anti-tumor function by blocking two inhibitory axes: CTLA-4/CD28 and PD1/PDL1. ICI is established as a treatment option for multiple cancers, but their remarkable clinical impact is observed only in a fraction of patients. Together with their adverse effects and high cost, it's imperative to identify patients who are likely to benefit from this type of treatment. Genomic features represent promising candidates as predictive biomarkers of response to ICI, with agnostic FDA-approvals of an anti-PD1 drug for tumors with microsatellite instability and tumors with a high mutational burden. Other genomic markers are also emerging to help refine patient selection. In this review, we discuss recent progress in genomic biomarkers development and its challenges, with a focus on alterations in the neoantigen burden, immune, and oncogenic pathways.
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Biomarcadores de Tumor/genética , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia/efectos adversos , Neoplasias/terapia , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/genética , Antígeno B7-H1/inmunología , Biomarcadores de Tumor/inmunología , Antígenos CD28/antagonistas & inhibidores , Antígenos CD28/genética , Antígenos CD28/inmunología , Antígeno CTLA-4/antagonistas & inhibidores , Antígeno CTLA-4/genética , Antígeno CTLA-4/inmunología , Genómica/tendencias , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias/genética , Neoplasias/inmunología , Neoplasias/patología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/genética , Receptor de Muerte Celular Programada 1/inmunologíaRESUMEN
Tumor mutational burden (TMB) reflects cancer mutation quantity. Mutations are processed to neo-antigens and presented by major histocompatibility complex (MHC) proteins to T cells. To evade immune eradication, cancers exploit checkpoints that dampen T cell reactivity. Immune checkpoint inhibitors (ICIs) have transformed cancer treatment by enabling T cell reactivation; however, response biomarkers are required, as most patients do not benefit. Higher TMB results in more neo-antigens, increasing chances for T cell recognition, and clinically correlates with better ICI outcomes. Nevertheless, TMB is an imperfect response biomarker. A composite predictor that also includes critical variables, such as MHC and T cell receptor repertoire, is needed.
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Biomarcadores de Tumor/inmunología , Mutación/genética , Mutación/inmunología , Neoplasias/genética , Neoplasias/inmunología , Biomarcadores de Tumor/genética , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Inmunoterapia/métodos , Complejo Mayor de Histocompatibilidad/genética , Complejo Mayor de Histocompatibilidad/inmunología , Neoplasias/terapia , Linfocitos T/inmunologíaRESUMEN
BACKGROUND: Immunosenescence biomarkers and peripheral blood parameters are evaluated separately as possible predictive markers of immunotherapy. Here, we illustrate the use of a causal inference model to identify predictive biomarkers of CIMAvaxEGF success in the treatment of Non-Small Cell Lung Cancer Patients. METHODS: Data from a controlled clinical trial evaluating the effect of CIMAvax-EGF were analyzed retrospectively, following a causal inference approach. Pre-treatment potential predictive biomarkers included basal serum EGF concentration, peripheral blood parameters and immunosenescence biomarkers. The proportion of CD8 + CD28- T cells, CD4+ and CD8+ T cells, CD4/CD8 ratio and CD19+ B cells. The 33 patients with complete information were included. The predictive causal information (PCI) was calculated for all possible models. The model with a minimum number of predictors, but with high prediction accuracy (PCI > 0.7) was selected. Good, rare and poor responder patients were identified using the predictive probability of treatment success. RESULTS: The mean of PCI increased from 0.486, when only one predictor is considered, to 0.98 using the multivariate approach with all predictors. The model considering the proportion of CD4+ T cell, basal Epidermal Growth Factor (EGF) concentration, neutrophil to lymphocyte ratio, Monocytes, and Neutrophils as predictors were selected (PCI > 0.74). Patients predicted as good responders according to the pre-treatment biomarkers values treated with CIMAvax-EGF had a significant higher observed survival compared with the control group (p = 0.03). No difference was observed for bad responders. CONCLUSIONS: Peripheral blood parameters and immunosenescence biomarkers together with basal EGF concentration in serum resulted in good predictors of the CIMAvax-EGF success in advanced NSCLC. Future research should explore molecular and genetic profile as biomarkers for CIMAvax-EGF and it combination with immune-checkpoint inhibitors. The study illustrates the application of a new methodology, based on causal inference, to evaluate multivariate pre-treatment predictors. The multivariate approach allows realistic predictions of the clinical benefit of patients and should be introduced in daily clinical practice.
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Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Biomarcadores de Tumor/sangre , Vacunas contra el Cáncer/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/terapia , Neoplasias Pulmonares/terapia , Modelos Estadísticos , Anciano , Biomarcadores de Tumor/inmunología , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/inmunología , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Ensayos Clínicos Fase III como Asunto , Terapia Combinada/métodos , Factor de Crecimiento Epidérmico/sangre , Factor de Crecimiento Epidérmico/inmunología , Femenino , Humanos , Inmunosenescencia , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Pronóstico , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios RetrospectivosRESUMEN
In diseases where epigenetic mechanisms are changed, such as cancer, many genes show altered gene expression and inhibited genes become activated. Human endogenous retrovirus type K (HERV-K) expression is usually inhibited in normal cells from healthy adults. In tumor cells, however, HERV-K mRNA expression has been frequently documented to increase. Importantly, HERV-K-derived proteins can act as tumor-specific antigens, a class of neoantigens, and induce immune responses in different types of cancer. In this review, we describe the function of the HERV-K HML-2 subtype in carcinogenesis as biomarkers, and their potential as targets for cancer immunotherapy.
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Retrovirus Endógenos , Inmunoterapia/métodos , Neoplasias/virología , Biomarcadores de Tumor/inmunología , Retrovirus Endógenos/genética , Retrovirus Endógenos/inmunología , Genoma Viral/genética , Humanos , Neoplasias/inmunología , Neoplasias/terapiaRESUMEN
Electrochemical immunosensors have been developed to determine the carbohydrate antigen 19-9 (CA19-9). They are based on screen-printed carbon electrodes (SPCEs) coated with layer-by-layer (LbL) films of carbon black (CB) and polyelectrolytes. Owing to a suitable choice of LbL film architecture, the procedures for immobilization of anti-CA19-9 antibodies on the electrode surfaces were straightforward. Mechanically flexible immunosensors were capable of detecting CA19-9 within a dynamic range of 0.01 to 40 U mL-1 and a limit of detection of 0.07 U mL-1 using differential pulse voltammetry. In addition to detecting CA19-9 at clinically relevant concentrations for pancreatic cancer in standard solutions, the immunosensors provide the determination of CA19-9 on cell lysate and human serum samples. Using LbL films led to immunosensors with superior performance compared to similar systems obtained by drop casting. The fabrication of this relatively simple, inexpensive platform is a demonstration that SPCEs modified with cost-effective materials are able to detect cancer biomarkers and may be adapted to other disposable immunosensors. Graphical abstract Schematic representation of assembly and characterization of electrochemical immunosensors for the determination of carbohydrate antigen 19-9 based on printed electrodes modified with composites of carbon black and polyelectrolyte films.
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Antígenos de Carbohidratos Asociados a Tumores/sangre , Biomarcadores de Tumor/sangre , Técnicas Electroquímicas/métodos , Inmunoensayo/métodos , Polielectrolitos/química , Hollín/química , Anticuerpos Inmovilizados/inmunología , Antígenos de Carbohidratos Asociados a Tumores/inmunología , Biomarcadores de Tumor/inmunología , Técnicas Electroquímicas/instrumentación , Electrodos , Humanos , Límite de DetecciónRESUMEN
Melanoma is a very lethal tumor type that easily spreads and colonizes regional and distant tissues. Crucial phenotypic changes that favor melanoma metastasis are interposed by the tumor microenvironment (TME), representing a complex network in which malignant cells communicate not only with each other but also with stromal and immune cells. This cell-cell communication can be mediated by extracellular vesicles (EVs), which are lipid bilayer-delimited particles capable of carrying a wide variety of bioactive compounds. Both melanoma-derived or TME-derived EVs deliver important pro- and antitumor signals implicated in various stages of tumor progression, such as proliferation, metastasis, and treatment response. In this review, we highlight the recent advances in EV-mediated crosstalk between melanoma and immune cells and other important cells of the TME, and address different aspects of this bidirectional interaction as well as how this may hinder or trigger the development and progression of melanoma. We also discuss the potential of using EVs as biomarkers and therapeutic strategies for melanoma.
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Biomarcadores de Tumor/inmunología , Comunicación Celular/inmunología , Proliferación Celular , Vesículas Extracelulares/inmunología , Melanoma/inmunología , Microambiente Tumoral/inmunología , Vesículas Extracelulares/patología , Humanos , Melanoma/patología , Melanoma/terapia , Metástasis de la NeoplasiaRESUMEN
BACKGROUND: Considering the potential of p16 as a marker for diagnosis, prognosis and therapeutic response, the aim of this study was to assess its presence, via immunocytochemistry, in metastatic carcinoma of different primary sites and histological types obtained from effusions and peritoneal washings. A total of 118 samples including 85 of metastatic carcinoma and 33 samples of benign effusion/peritoneal washing were prepared by the plasma/thromboplastin method. Immunocytochemistry reactions were performed on cell block sections using antibodies against p16, claudin-4, MOC-31, calretinin, HBME and CD68. RESULTS: P16 overexpression was observed in 88.23% of all carcinoma samples. All cervix adenocarcinoma samples showed p16 overexpression. Overexpression in adenocarcinomas of ovary, lung and breast was observed in 93.75, 93.10 and 75% of the samples, respectively. Overexpression was observed in all different histological types analyzed: small cell carcinoma (lung), squamous cell carcinoma (cervical) and urothelial carcinoma (bladder). The specificity of p16 for carcinoma detection was of 96.96%. CONCLUSION: Overexpression of p16 was observed in most metastatic carcinoma, from different primary sites and histological types, obtained from effusions and peritoneal washings. Due to its high frequency of overexpression in metastatic carcinoma, p16 may play a possible role in tumor progression and it may be considered as a complementary diagnostic marker depending on histological type and primary site of carcinoma.
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Líquido Ascítico/química , Biomarcadores de Tumor/análisis , Carcinoma/diagnóstico , Carcinoma/secundario , Inhibidor p16 de la Quinasa Dependiente de Ciclina/análisis , Neoplasias/diagnóstico , Neoplasias/patología , Derrame Pericárdico/química , Derrame Pleural Maligno/química , Antígenos CD/análisis , Antígenos CD/inmunología , Antígenos de Diferenciación Mielomonocítica/análisis , Antígenos de Diferenciación Mielomonocítica/inmunología , Antígenos de Superficie/análisis , Antígenos de Superficie/inmunología , Biomarcadores de Tumor/inmunología , Calbindina 2/análisis , Calbindina 2/inmunología , Claudina-4/análisis , Claudina-4/inmunología , Inhibidor p16 de la Quinasa Dependiente de Ciclina/inmunología , Molécula de Adhesión Celular Epitelial , Humanos , PronósticoRESUMEN
The existence of cancer stem cells is debatable in numerous solid tumors, yet in leukemia, there is compelling evidence of this cell population. Leukemic stem cells (LSCs) are altered cells in which accumulating genetic and/or epigenetic alterations occur, resulting in the transition between the normal, preleukemic, and leukemic status. These cells do not follow the normal differentiation program; they are arrested in a primitive state but with high proliferation potential, generating undifferentiated blast accumulation and a lack of a mature cell population. The identification of LSCs might guide stem cell biology research and provide key points of distinction between these cells and their normal counterparts. The identification and characterization of the main features of LSCs can be useful as tools for diagnosis and treatment. In this context, the aim of the present review was to connect immunophenotype data in the main types of leukemia to further guide technical improvements.
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Inmunofenotipificación/tendencias , Leucemia/diagnóstico , Leucemia/inmunología , Células Madre Neoplásicas/inmunología , Biomarcadores de Tumor/inmunología , Biomarcadores de Tumor/uso terapéutico , Diferenciación Celular/inmunología , Citometría de Flujo , Humanos , Leucemia/patología , Leucemia/terapia , Células Madre Neoplásicas/patología , PronósticoRESUMEN
BACKGROUND: Recent studies indicate that serum from cancer patients contains auto-antibodies against oncoproteins so called tumor-associated antigens (TAAs), which represent promising diagnostic and prognostic biomarkers. OBJECTIVES: In this study we searched for breast cancer-associated auto-antibodies against individual TAAs. Also we evaluated if a panel of multiple TTAs would improve the detection of auto-antibodies. We screened CEA, CCBN1, c-Myc, p53, Ki-67, Nm23, PRDX6, eIF5A, PARK7, GLIO-1, Hsp27 and Hsp70 proteins, previously detected as up-regulated in breast tumors of Mexican patients. METHODS: Enzyme-linked immunosorbent assays (ELISA) were performed to detect auto-antibodies in sera from a cohort of 104 breast cancer patients and 50 sera from healthy individuals. RESULTS: Our data showed that antibodies frequency to any individual TAA was low and ranged from 0.96% to 4.8%. However, the successive addition of multiple TAAs represented by panels of three-to-five TAAs resulted in increased ELISA positive reactions. The first panel of three combined TAAs (p53/PRDX6/CEA) had a sensitivity of 19%, while a second set of four TAAs (p53/PRDX6/c-Myc/Hsp70) reached 28% sensitivity. Likewise, a third panel of five antigens (p53/PRDX6/c-Myc/Hsp70/Nm23) showed 34% sensitivity. CONCLUSIONS: Our data showed that detection of individual autoantibodies against TAAs in the cohort of patients analyzed here was low, which was enhanced by adding multiple TAAs. Data support the notion that frequencies of autoantibodies could be impacted by geographical and heterogeneous genetic factors of breast cancer patients.
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Antígenos de Neoplasias/sangre , Autoanticuerpos/sangre , Biomarcadores de Tumor/inmunología , Neoplasias de la Mama/inmunología , Adulto , Anciano , Antígenos de Neoplasias/inmunología , Autoanticuerpos/inmunología , Biomarcadores de Tumor/sangre , Neoplasias de la Mama/sangre , Neoplasias de la Mama/diagnóstico , Estudios de Casos y Controles , Estudios de Cohortes , Ensayo de Inmunoadsorción Enzimática/métodos , Femenino , Humanos , Persona de Mediana Edad , Curva ROCRESUMEN
LiTCTP is a toxin from the Translationally Controlled Tumor Protein (TCTP) family identified in Loxosceles brown spider venoms. These proteins are known as histamine-releasing factors (HRF). TCTPs participate in allergic and anaphylactic reactions, which suggest their potential role as therapeutic targets. The histaminergic effect of TCTP is related to its pro-inflammatory functions. An initial characterization of LiTCTP in animal models showed that this toxin can increase the microvascular permeability of skin vessels and induce paw edema in a dose-dependent manner. We evaluated the role of LiTCTP in vitro and in vivo in the inflammatory and allergic aspects that undergo the biological responses observed in Loxoscelism, the clinical condition after an accident with Loxosceles spiders. Our results showed LiTCTP recombinant toxin (LiRecTCTP) as an essential synergistic factor for the dermonecrotic toxin actions (LiRecDT1, known as the main toxin in the pathophysiology of Loxoscelism), revealing its contribution to the exacerbated inflammatory response clinically observed in envenomated patients.
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Biomarcadores de Tumor/inmunología , Hipersensibilidad/inmunología , Inflamación/inmunología , Hidrolasas Diéster Fosfóricas/química , Hidrolasas Diéster Fosfóricas/inmunología , Enfermedades de la Piel/inmunología , Venenos de Araña/química , Venenos de Araña/inmunología , Animales , Biomarcadores de Tumor/antagonistas & inhibidores , Biomarcadores de Tumor/genética , Cimetidina/administración & dosificación , Cimetidina/farmacología , Cromolin Sódico/administración & dosificación , Cromolin Sódico/farmacología , Relación Dosis-Respuesta a Droga , Hipersensibilidad/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Inyecciones Intraperitoneales , Inyecciones Intravenosas , Mastocitos/efectos de los fármacos , Mastocitos/inmunología , Ratones , Piperidinas/administración & dosificación , Piperidinas/farmacología , Prometazina/administración & dosificación , Prometazina/farmacología , Conejos , Ratas , Enfermedades de la Piel/tratamiento farmacológico , Células Tumorales Cultivadas , Proteína Tumoral Controlada Traslacionalmente 1RESUMEN
BACKGROUND: Human papillomavirus (HPV) infection is the central factor for cervical cancer, whereas epithelial immune mechanisms contribute to the progression of HPV infection and its associated lesions. The authors evaluated the expression of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) in cervicovaginal samples from women with normal cervical epithelium or with different degrees of squamous intraepithelial lesions (SILs) and cervical cancer. METHODS: IDO expression was analyzed by immunocytochemistry in liquid-based cytology samples from 165 women, of whom 42 had cervical changes subclassified as low-grade SIL (n = 6), high-grade SIL (n = 30), or squamous cell carcinoma (SCC) (n = 6), and 123 had negative Papanicolaou smears. IDO and TDO expression also were analyzed by immunohistochemistry, and HPV and other genital pathogens were evaluated by polymerase chain reaction analysis. RESULTS: Low IDO expression was observed in normal cervical epithelium irrespective of HPV status. Increased numbers of IDO-positive squamous cells and IDO-positive leukocytes were observed in women with SIL or SCC. TDO expression was detected in leukocytes infiltrating the stroma around intraepithelial or invasive cervical lesions. Higher IDO levels were detected in organotypic epithelial cultures established from keratinocytes transduced with the HPV16 E6/E7 oncoproteins. CONCLUSIONS: The upregulation of IDO expression in leukocytes and squamous cells in HPV-associated SIL and SCC suggests that immunosuppressive mechanisms involving tryptophan metabolism may have a role in cervical carcinogenesis. Although previous studies have suggested the role of IDO in HPV pathogenesis, this is the first evidence of TDO involvement in the process. Furthermore, the current data emphasize the role of leukocytes, especially neutrophil-like cells, as an IDO source.
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Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/patología , Indolamina-Pirrol 2,3,-Dioxigenasa/metabolismo , Infecciones por Papillomavirus/patología , Triptófano Oxigenasa/metabolismo , Displasia del Cuello del Útero/patología , Neoplasias del Cuello Uterino/patología , Biomarcadores de Tumor/inmunología , Carcinogénesis/inmunología , Carcinogénesis/patología , Carcinoma de Células Escamosas/inmunología , Carcinoma de Células Escamosas/virología , Cuello del Útero/inmunología , Cuello del Útero/patología , Cuello del Útero/virología , Femenino , Humanos , Indolamina-Pirrol 2,3,-Dioxigenasa/inmunología , Persona de Mediana Edad , Oligopéptidos , Prueba de Papanicolaou , Papillomaviridae/inmunología , Papillomaviridae/aislamiento & purificación , Papillomaviridae/patogenicidad , Infecciones por Papillomavirus/inmunología , Infecciones por Papillomavirus/virología , Triptófano Oxigenasa/inmunología , Regulación hacia Arriba , Neoplasias del Cuello Uterino/inmunología , Neoplasias del Cuello Uterino/virología , Frotis Vaginal , Displasia del Cuello del Útero/inmunología , Displasia del Cuello del Útero/virologíaRESUMEN
Early diagnosis of cancer by biomarker detection has been widely studied since it can lead to an increase in patient survival rates. Magnetic nanoparticles (MNPs) play an important role in this field acting as a valuable tool in the biomarker immunocapture and detection. In this work, Co0.25Zn0.75Fe2O4 (CoZnFeONPs) nanoparticles were synthesized and applied as enzyme mimics of peroxidase-like catalysis in a disposable enzyme-free microfluidic immunoarray device (µID). The catalytic activity of CoZnFeONPs was evaluated by hydrogen peroxide detection using cyclic voltammetry and the apparent Michaelis-Menten constant was estimated by Lineweaver-Burk equation showing good Km values. In µID, the immunosensors were assembled with monoclonal antibody against CYFRA 21-1 covalently immobilized on graphene oxide previously deposited on the screen-printed carbon-based electrodes. Under optimized conditions, the method presented a good linear response for CYFRA 21-1 in the range of 3.9-1000â¯fgâ¯mL-1 achieving an ultralow limit of detection (LOD) of 0.19â¯fgâ¯mL-1. For comparison, Fe3O4 nanoparticles (FeONPs) was also synthetized and presented results slight inferior to that obtained with CoZnFeONPs. The methods developed using both MNPs exhibited countless advantages when compared with the immunosensors developed for CYFRA-21-1, previously reported in the literature. The methods were successful applied for the detection of CYFRA 21-1 in real serum samples of healthy and prostate cancer patients and showed good correlation with results obtained with the enzyme-linked immunosorbent assay (ELISA). The CoZnFeONPs associated with the disposable microfluidic immunoarray device provides a simple and effective method for biomarker detection that could satisfy the need for a low-cost and rapid test for early diagnosis of cancer.
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Antígenos de Neoplasias/sangre , Biomarcadores de Tumor/sangre , Queratina-19/sangre , Dispositivos Laboratorio en un Chip , Nanopartículas del Metal/química , Técnicas Analíticas Microfluídicas/métodos , Anticuerpos/inmunología , Antígenos de Neoplasias/inmunología , Biomarcadores de Tumor/inmunología , Cobalto/química , Electrodos , Grafito/química , Humanos , Inmunoensayo/instrumentación , Inmunoensayo/métodos , Hierro/química , Queratina-19/inmunología , Límite de Detección , Masculino , Técnicas Analíticas Microfluídicas/instrumentación , Neoplasias de la Próstata/sangre , Reproducibilidad de los Resultados , Zinc/químicaRESUMEN
Breast cancer is characterized by cellular and molecular heterogeneity. Several molecular events are involved in controlling malignant cell process. In this sense, the importance of studying multiple cell alterations in this pathology is overriding. A well-identified fact on immune response is that it can vary depend on sex. Steroid hormones and their receptors may regulate different functions and the responses of several subpopulations of the immune system. Few reports are focused on the function of estrogen receptors (ERs) on immune cells and their roles in different breast cancer subtypes. Thus, the aim of this review is to investigate the immune infiltrating tumor microenvironment and prognosis conferred by it in different breast cancer subtypes, discuss the current knowledge and point out the roles of estrogens and its receptors on the infiltrating immune cells, as well as to identify how different immune subsets are modulated after anti-hormonal treatments in breast cancer patients.