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Purpose Penile cancer has a high incidence in developing countries. The standard treatment is removal of the primary tumor and, when necessary, inguinal lymphadenectomy. Currently the most important prognostic factor is lymph node disease, however the available staging methods are inaccurate, and the high morbidity rate of lymphadenectomy has stimulated the study of predictive biomarkers of lymph node metastasis for selecting the patients who need lymphadenectomy. SOX2, STAT3 and CD44high/CD24low were chosen because they have provided good predictive results in other squamous cell carcinoma (SCC), although there are no studies for penile cancer. Thus, the expression of SOX2, STAT3, CD24+, and CD44 + in the penile cancer tumor microenvironment was investigated for correlation with tumor behavior in SCC. Methods This observational, prospective, translational study included 34 men and investigated the expression of SOX2, STAT3, CD24+, and CD44 + in tumor tissue by flow cytometry. Results The median age of the 38 evaluated patients with penile cancer was 61 (37–80) years. Most patients presented a tumor located on the glans penis (82.3%), with the usual histological type (79.4%) and 61.7% of patients presented stage pT2. No metastasis was found in 85.3% of patients. The expression of SOX2, STAT3 and CD44high/CD24low in the microenvironment of penile SCC treated with lymphadenectomy was significantly associated with aggressive tumor behavior (p high/CD24low in penile SCC can be indicators of prognosis, allowing for selection of more aggressive treatment when necessary.

The extracellular matrix plays an important role in cellular balance, and collagen fibers are its most important component. Over the last few years, second harmonic generation (SHG) microscopy has been used for the analysis of collagen fibers in several types of gynaecological cancers, such as breast and ovarian cancer. The value of collagen parameters obtained with this technique to gain insights on the physiopathology and on the prognostic evaluation of cancer has been advocated. Herein, we have characterized the collagen fibers in squamous cell carcinoma (VSCC) and preneoplastic lesions using the SHG microscopy. Collagen parameters, quantity, organization, and uniformity, of VSCC, adjacent skin of VSCC or preneoplastic lesions were compared with values obtained in normal tissue of healthy control. There was an evident decrease in the values of collagen fiber parameters in the VSCC. Increased quantity and uniformity of tumor associated collagen fibers were associated with the presence of lymph node metastases, which suggest a prognostic value of such parameters in the evaluation of vulvar cancer.

Background: The immune system is recognized to have therapeutic potential to destroy cancer cells. T-cell immunoglobulin mucin domain-3 (sTIM-3) and its ligand galectin 9 (GAL9) cause suppression of cytokine production, cell cycle arrest, and cell death. Then, soluble levels of TIM-3 and GAL-9 may have prognostic implications in non-small-cell lung cancer (NSCLC) in non-smoker patients. Methods: This prospective cohort study, including 49 NSCLC patients with an age median of 65 years, evaluated the soluble levels of sTIM-3 and sGAL9 by enzyme-linked immunosorbent assay. Results: Low levels of sGAL9 in smokers compared to non-smoker NSCLC patients (P

BackgroundLike HPV types, different lineages also appear to have different carcinogenic capabilities. Studies have shown that oncogenic HPV specific to the genotype lineage is associated with different risks for the development of cervical intraepithelial neoplasia (CIN2 / CIN3) and cervical cancer. This study aims to analyze the genetic diversity of HPV 16 genotype in cases of cervical intraepithelial neoplasia (CIN2/CIN3) and cervical cancer in women from the Northeast region of Brazil.Methods and ResultsA cross-sectional hospital-based study conducted in the Northeast region of Brazil from 2014 through 2016. In the sample, there were 196 cases of HPV-16 variant (59 cervical intraepithelial neoplasia - CIN2/CIN3 and 137 cases of cervical cancer). Difference of proportion test was used to compare groups of CIN2/CIN3 and cervical cancer by viral lineage (p-value

The p90 ribosomal S6 kinase (RSK) family, a downstream target of Ras/extracellular signal‐regulated kinase signaling, can mediate cross‐talk with the mammalian target of rapamycin complex 1 pathway. As RSK connects two oncogenic pathways in gliomas, we investigated the protein levels of the RSK isoforms RSK1–4 in nontumoral brain (NB) and grade I‐IV gliomas. When compared to NB or low‐grade gliomas (LGG), a group of glioblastomas (GBMs) that excluded long‐survivor cases expressed higher levels of RSK1 (RSK1hi). No difference was observed in RSK2 median‐expression levels among NB and gliomas; however, high levels of RSK2 in GBM (RSK2hi) were associated with worse survival. RSK4 expression was not detected in any brain tissues, whereas RSK3 expression was very low, with GBM demonstrating the lowest RSK3 protein levels. RSK1hi and, to a lesser extent, RSK2hi GBMs showed higher levels of phosphorylated RSK, which reveals RSK activation. Transcriptome analysis indicated that most RSK1hi GBMs belonged to the mesenchymal subtype, and RSK1 expression strongly correlated with gene expression signature of immune infiltrates, in particular of activated natural killer cells and M2 macrophages. In an independent cohort, we confirmed that RSK1hi GBMs exclude long survivors, and RSK1 expression was associated with high protein levels of the mesenchymal subtype marker lysosomal protein transmembrane 5, as well as with high expression of CD68, which indicated the presence of infiltrating immune cells. An RSK1 signature was obtained based on differentially expressed mRNAs and validated in public glioma datasets. Enrichment of RSK1 signature followed glioma progression, recapitulating RSK1 protein expression, and was associated with worse survival not only in GBM but also in LGG. In conclusion, both RSK1 and RSK2 associate with glioma malignity, but displaying isoform‐specific peculiarities. The progression‐dependent expression and association with immune infiltration suggest RSK1 as a potential progression marker and therapeutic target for gliomas., RSK1 protein levels are higher in a subpopulation of glioblastomas (RSK1hi GBMs) than in low‐grade gliomas and also after recurrence. Long‐survivor cases are excluded from RSK1hi GBMs. Transcriptome analysis of RSK1hi GBMs indicates the presence of immune infiltrate. An RSK1 gene signature recapitulates the increase in RSK1 levels in higher‐grade gliomas, and its enrichment is associated with poor survival.

Objective To describe the immunological and hematological reference intervals of low-risk pregnant women. Methods A cross-sectional retrospective database analysis of a basic and translational study analyzing the hematological evaluation blood counts and immunophenotyping of TCD3 + , TCD4 + , TCD8 + , B, and natural killer (NK) cells of the peripheral blood in 79 low-risk pregnant women and of 30 control women from the state of Pernambuco, Brazil, was performed. Results No significant differences were detected between the hematological profiles of the 2nd and 3rd trimesters. Nevertheless, the median level of B cells decreased significantly in the 2nd (174 x 103 μL; p < 0.002) and 3rd trimesters (160 x 103 μL; p < 0.001), compared with the control group (296 x 103 μL). Similarly, the median level of NK cells was lower in the 2nd (134 x 103 μL; p < 0.0004) and 3rd trimesters (100 x 103 μL, p < 0.0004), compared with the control group (183 x 103 μL). In contrast, relative TCD4+ and TCD8+ levels increased in the 2nd and 3rd trimesters compared with the controls (TCD4 + : 2nd trimester = 59%; p < 0.001; 3rd trimester = 57%; p < 0.01; control = 50%; and TCD8 + : 2nd trimester = 31%; p < 0.001; 3rd trimester = 36%; p < 0.01; control = 24%). Conclusion Low-risk pregnant women have ~ 40% less B and NK cells in the peripheral blood, compared with non-pregnant women. These parameters may improve health assistance for mothers and contribute to define reference values for normal pregnancies. Resumo Objetivo Descrever o intervalo de referência imunológico e hematológico de gestantes de baixo risco. Métodos Realizou-se uma análise retrospectiva, de um estudo básico e translacional, analisando o perfil hematológico e a imunofenotipagem das células TCD3 + , TCD4 + , TCD8 + , B e natural killer (NK) do sangue periférico de 79 gestantes de baixo risco e de 30 mulheres (controles) do estado de Pernambuco, Brasil. Resultados Não observamos diferenças significativas entre os perfis hematológicos do 2° e 3° trimestres. No entanto, houve redução das células B no 2° (média = 174 x 103 μL; p < 0,002) e no 3° trimestres (160 x 103 μL; p < 0,001), comparado como grupo controle (296 x 103 μL). A mediana das células NK foi menor no 2° (134 x 103 μL; p < 0,0004) e no 3° trimestres (100 x 103 μL; p < 0,0004), comparado com o grupo controle (183 x 103 μL). Porém, o percentual de TCD4+ e de TCD8+ aumentou no 2° e 3° trimestres em relação aos controles (TCD4 + : 2° trimestre = 59%; p < 0,001; 3° trimestre = 57%; p < 0,01; controle = 50%; e TCD8 + : 2° trimestre = 31%; p < 0,001; 3° trimestre = 36%; p < 0,01; controle = 24%). Conclusão Mulheres grávidas de baixo risco têm ~ 40% menos células B e NK no sangue periférico em comparação com mulheres não grávidas. Estes parâmetros podem melhorar a assistência à saúde das mães e contribuir para a definição de valores de referência para gestações normais.

Objective: To assess the levels of CD80 and CD86-expressing B lymphocytes in the blood of women with locally advanced triple-negative breast cancer (TNBC). Methods: This is a prospective and exploratory cohort study involving 30 women with TNBC and 30 healthy controls, conducted in 2018–2019. Peripheral blood collection was performed prior to chemotherapy. Immunophenotyping of B lymphocytes and CD80 and CD86 molecules was performed by flow cytometry. Women were evaluated for the degree of pathological response to chemotherapy and divided into groups with full (RC) or partial (RP) pathological response. Nonparametric Mann–Whitney U-test was used for comparison between two groups. Values of p

Objective: To evaluate the levels of circulating platelet–leukocyte aggregates in women with breast cancer (BC). Methods: A cross-sectional study was carried out between 2018 and 2019 with 27 women, who aged between 18 and 60 years, diagnosed with BC and 15 healthy women (controls). For the evaluation of the circulating platelet aggregate, samples of peripheral blood were collected at the time of routine laboratory tests for diagnosis and before treatment. Platelet aggregate analysis was performed using monoclonal antibodies by flow cytometry. Mann–Whitney U and Kruskal–Wallis tests were used to analyze medians between two and three groups, respectively. Values of p

Regular physical activity prevents and treats cancer patients by assisting and improving the immune system. Co-stimulatory molecules that activate the immune system have been studied in cancer, such as immune checkpoint molecules of the CD40/CD40L pathway. This study aimed to characterize plasma levels of soluble CD40 (sCD40) and CD40 ligand (sCD40L) in older people with gastrointestinal tract (GIT) cancer and associate results with physical activity. This prospective and exploratory cohort study was performed with 24 older people with GIT cancer and 23 healthy elderly individuals as controls. Physical activity level was classified as active or sedentary according to the International Physical Activity Questionnaire-Short Form (IPAQ-SF). Plasma levels of sCD40 and sCD40L were determined using Enzyme-Linked Immunosorbent Assay. Plasma levels of sCD40 were higher, while sCD40L were lower (p = 0.0171) in older people with GIT cancer than controls (p = 0.0038). Regarding physical activity, active older people with GIT cancer presented lower plasma levels of sCD40 and sCD40L than those sedentary with GIT cancer (p = 0.0228 and p = 0.0236), respectively. Our findings suggest that GIT cancer stimulates the immune system in older people, elevates levels of sCD40, and reduces levels of sCD40L. Physical activity may be a protective factor for the immune system of these patients since it acts on sCD40/sCD40L pathway.

BACKGROUND AND OBJECTIVES The prognosis of colorectal cancer (CRC) has improved in the last decades, however, a lower overall survival persists in the elderly. The understanding of immunity changes in the elderly with CRC will allow the emergence of new treatments with higher response rates. 4-1BB and CD40L, an immune checkpoint stimulator, play an important role in T-cell responses and platelets. Our aim was to characterize the soluble levels of CD40L and 4-1BB in CRC elderly patients. METHODS A cross-sectional study was performed in 41 patients with CRC and 35 healthy elderly controls. Patients with CRC were divided into three groups according to staging: 13 patients with advanced tumor restricted to the organ (stages II); 16 patients with lymph node metastasis (stage III); and 12 patients with distant metastasis (stage IV). RESULTS There were higher levels of soluble s4-1BB and sCD40L in CRC elderly stage II patients when compared with healthy controls (P = .0009 and P

Gastric cancer is one of the most common cancers, and an increasing number of studies have found that microRNAs (miRNAs) play essential roles in gastric cancer progression; however, the roles of specific miRNAs involved in the immune response to this disease remain unclear. We compared the miRNA expression in tissues from primary gastric cancer patients and healthy controls to find miRNAs dysregulated in gastric cancer and used bioinformatics tools to determine potential roles of these miRNAs in the immune system. We evaluated 25 primary gastric cancer tissues and five healthy gastric tissues. Quantitative real-time polymerase chain reaction was performed for a set of miRNAs, followed by the prediction of their target genes and functional enrichment analysis of these targets. Analysis of a microarray dataset showed that the miRNA miR-196a-5p was significantly upregulated, while miR-374a-5p and miR-375 were downregulated in gastric cancer patients. In addition, miR-374-5p was significantly downregulated in patients with metastasis compared with its expression levels in non-metastatic patients (p = 0.03). Bioinformatics analysis suggested that the pathways regulated by these differentially expressed miRNAs were related to the immune response, cell adhesion, and cell migration. Most importantly, this study provides a new insight into the potential use of multiple miRNAs to find distinct pathways of immune regulation in gastric cancer.

Among the lysosomal storage disorders, Gaucher disease (GD) features some of the most striking alterations in the immune system, including increased levels of cytokines and chemokines. Although studies have demonstrated the efficacy of enzyme replacement therapy (ERT) for GD, the ideal dosage remains controversial. In this study, we report differences in levels of cytokines (IL-6, TNF-a, and IFN-y) and chemokines (IL-8, IP-10, and MCP-1) in patients with GD type 1 treated with different ERT dosages and treatment durations. Patients were recruited from two ERT centers in Brazil and divided into two groups according to treatment facility. Comparison between groups showed that patients in group 1 had received ERT for longer (p=0.0078) and at higher doses (p=0.0002) than those in group 2. Patients in group 1 exhibited decreased levels of IL-6 (p=0.0006), TNF-α (p

22q11.2 deletion syndrome (22q11.2DS) has a heterogeneous presentation that includes multiple congenital anomalies and immunodeficiency, one of the most striking features. Usually, it is characterized by T cell lymphopenia, B cell dysfunction and autoimmunity. Here, we describe an unusual case of 22q11.2DS in a patient with lymphoproliferative disorder, polyautoimmunity and hypogammaglobulinemia.

OBJECTIVE To determine the prevalence of anal HPV genotypes and associated factors in women with pre-malignant lesion or cancer in the cervix and anal canal. METHODS A prospective, cross-sectional study analyzed DNA samples taken from women with cervical pre-malignant lesions or cancer to identify anal HPV by polymerase chain reaction (PCR). The prevalence of high-risk HPV (HR-HPV) in women with intraepithelial neoplasia and anal cancer was calculated; sociodemographic and clinical risk factors were identified using multivariate analysis. RESULTS A total of 152 patients were included (mean age 37.8 ± 10.01 years), of whom 101 (66.4%) had anal HR-HPV. Fourteen different anal HPV types were identified. HPV 16 and 18 were found in 30 (52.6%) anal high-grade squamous intraepithelial lesions (HSIL), and HPV 31 and 33 in 21 (36.8%) lesions. In the logistic regression analysis, the factors that remained associated with HR-HPV types were: an anal histopathology report of HSIL or invasive carcinoma (odds ratio [OR] 8.96, 95% confidence interval [CI] 3.40-23.57; P

Pregnancy in sickle cell disease is a problem due to the adverse outcomes related to the disease. Research into the role of chemokines in sickle cell disease is available, but studies investigating the disease in pregnancy are scarce. Our data show the chemokine profiles of pregnant women with sickle cell disease compared with control groups. There were no differences in MCP-1 level among the groups, but IL-8 and MIG were likely related with disease activity. In addition, levels of IP-10 were higher in pregnant women with sickle cell disease and, interestingly, RANTES levels were higher in normal pregnancy when compared to pregnancy in sickle cell disease. More studies should be encouraged to fully elucidate chemokine activity during pregnancy in sickle cell disease.

The mucopolysaccharidoses (MPSs) are a group of rare, inherited lysosomal storage disorders that are clinically characterized by abnormalities in multiple organ systems and reduced life expectancy. Whereas the lysosome is essential to the functioning of the immune system, some authors suggest that the MPS patients have abnormalities in the immune system similar to the patients with primary immunodeficiency. In this study, we evaluated 8 male MPS type II patients of the same family with novel mutation in the IDS gene. We found in this MPS family a quantitative deficiency of NK and B cells with normal values of IgG, IgM and IgA serum antibodies and normal response to polysaccharide antigens. Interestingly, abnormalities found in these patients were not observed in other MPS patients, suggesting that the type of mutation found in the IDS gene can be implicated in the immunodeficiency.

Background To identify markers for earlier diagnosis of severe pneumonia, we assess the correlation between serum cytokine profile of children with different pneumonia severity. Methods In 25 hospitalized children, 7 with mild pneumonia and 18 with severe pneumonia, the serum concentration of 11 cytokines in three sampling times were dosed. Statistical analysis included parametric and non-parametric tests, Pearson correlation and ROC curve for cut-off definition of cytokines. Results At admission, IL-6 serum levels were high in mild or severe pneumonia, and was associated to vomiting (P = 0.019) in both groups; and also to dyspnea (P = 0.012) and white blood cell count (P = 0.045) in patients with severe pneumonia. IL-10 levels were also high in patients with pneumonia and were associated to lymphocytosis (P = 0.025). The ROC curve of the IL-6:IL-10 serum levels ratio discriminated severe pneumonia cases at admission, and persistence of infection in the third day of antibiotic therapy, with positive predictive values of 93% and 89%, respectively. Conclusions The balance between IL-6 and IL-10 serum levels showed to be a more discriminative marker for severity definition and evaluation of recovery in patients with pneumonia. Electronic supplementary material The online version of this article (doi:10.1186/s12890-016-0324-z) contains supplementary material, which is available to authorized users.

Chemokines are chemotactic cytokines that are mainly involved in the migratory patterns of immune cells. Few studies have evaluated the levels of chemokines in children with acute bacterial infections. The aim of this study was to evaluate the serum levels of chemokines MCP-1, RANTES, MIG and IP-10 in children with sepsis, community-acquired pneumonia (CAP) and skin abscess. Serum levels of MCP-1, RANTES, MIG and IP-10 were measured in 37 children with sepsis, 27 children with CAP, 25 children with skin abscess and 20 controls with no signs of infection. Patients with sepsis, CAP and skin abscess had higher concentrations of RANTES compared to controls (P = 0.0057, P = 0.0004 and P = 0.0108, respectively). IP-10 values were higher in patients with sepsis compared to children with skin abscess (P = 0.0075). However, MCP-1 levels were lower in septic patients compared to controls (P = 0.0136). There was no difference on MIG concentrations between the groups. Our original findings observed that RANTES was consistently elevated in all types of infections suggesting this chemokine may play an important role in the pathogenesis of bacterial infection. Additionally, patients with sepsis had a unique pattern of response with high levels of IP-10 but low levels of MCP-1, which should be further explored as the markers of disease severity.

e17074Background: Toll-Like Receptors (TLRs) are important in oncology research due to its role in the activation of various biological factors, inflammation and its influence on tumor progression....

e24142Background: Elderly cancer group is a heterogeneous and growing one. In the elderly, Toll-Like Receptors(TLRs) have been described as related to the immunosenescence process, carcinogenesis a...

A síndrome de Rubinstein-Taybi (RTS, OMIM 180849) é uma doença autossômica dominante caracterizada por dismorfismos craniofaciais típicos, polegares e háluces alargados, infecções respiratórias recidivantes, retardo mental e de crescimento. RTS está associada com mutação no gene CREBBP. Na avaliação da imunocompetência de 17 portadores de RTS, observaram-se algumas alterações na resposta imune inata e adaptativa: leucocitose persistente, neutrófilos com desgranulopoiese, elevada concentração sérica de IgM e IgG1, produção normal de anticorpos contra antígenos protéicos e anti-polissacarídeos, elevados valores absolutos de células B totais, B \"naive\", B de memória, subpopulação B1 e de linfócitos B com IgM de membrana, e elevado percentual de apoptose de linfócitos B. DTH negativo para três antígenos e baixa resposta linfoproliferativa para antígenos protéicos. Diante do exposto, concluímos que os pacientes RTS apresentam alterações em vários mecanismos da resposta imune e principalmente, na imunidade humoral. Portanto, com este trabalho foi possível identificar as principais alterações imunológicas destes pacientes, e com isso, caracterizar quais os defeitos da resposta imune que pode estar associada com gene CREBBP. Rubinstein-Taybi syndrome (RTS, OMIM 180849) is a dominant Mendelian disorder characterized by craniofacial dysmorphisms, broad thumbs and toes, mental retardation and growth and recurrent respiratory infections. RTS is classically associated with CREBBP gene mutations, but recently, p300 gene mutations were reported in three individuals. In imunonocompetence investigation of a group of 17 patient of the RTS, we found that the patients really show alterations in more than one arm of the immune response. The main alterations were found in: a) innate immunity, patients have defects in the distribution of the granules citoplasmatic and partial absence of F-actin filament part of its polymorphonuclear cells. In addition, some patients had decreased phagocytic activity, b) humoral immunity: elevated serum IgM antibodies and IgG1 subclass, normal production of antibodies for protein antigens and antipolysaccharide, high absolute values of B cell total, B \"naive\", B memory, subpopulation B1 and B lymphocytes with the membrane IgM, and high percentage of apoptosis of B lymphocytes; c) cellular immunity: delayed hypersensitivity skin tests negative for three antigens and low lymphoproliferative response to protein antigens. Values reduced percentage of CD45RA+ , CD45RO+ T cells and high doublepositive CD45RA+/CD45RO +) T cell. Ahead of the severe recurrent respiratory infections that affect the patients with RTS, and of the evaluation of immunocompetence of these patients, we find that they have several alterations in mechanisms of immune response and mainly in humoral immunity. Therefore, with this study was to identify the major immunological alterations of these patients, and with this, which characterize the main defects of the immune response of the patients RTS that can is associated with gene CREBBP.

Gaucher Disease (GD) is a rare autosomal recessive disorder caused by the deficient activity of beta-glucocerebrosidase. GD is one of the lysosomal storage diseases with the most remarkable alterations in the immune system, and that may manifest clinically as autoimmune disorders and malignancy. We reported the immunological evaluation of a patient with GD and lupus nephritis. Decreased absolute values of T, and NK, and an inversion of CD4(+)/CD8(+) ratio, low levels of IgM and normal B cells were found when compared to reference values in a Brazilian population. Absence ofCD4(+)CD25(high)Foxp3(+) Treg and high levels of total NKT, iNKT cells and CD8(+) iNKT subsets were also observed when compared to the healthy control and GD patient without lupus nephritis. Treg subset and CD8(+) iNKT abnormalities might be involved in severe lupus nephritis in a GD patient. We conclude by emphasizing the importance of the immunological evaluation on early diagnosis of autoimmunity contributing to reduce mortality and morbidity of these patients.

Rubinstein-Taybi syndrome (RTS) is a rare developmental disorder characterized by craniofacial dysmorphisms, broad thumbs and toes as well as mental and statural deficiencies.1 RTS has a prevalence of 1 in 330,000 births2 and usually occurs sporadically, although it can be inherited as an autosomal dominant disorder.2,4 The diagnosis is based on characteristic features.3 The main clinical symptoms are failure to thrive, cardiac defects and recurrent respiratory infections.4 Other variable findings are colobomas, cataracts, renal anormalities3,4 and oro-dental anomalies.5 RTS patients also have an increased risk of developing neoplasias.6,7 Several tumors have been reported in RTS patients, including meningiomas, rhabdomyosarcomas, neuroblastomas, oligodendromas, seminomas, choristomas and leukemias.6,7 CREBBP and EP300 are the only genes associated with RTS.8,11 Microdeletions at band 16p13.3 occur in 10%–25% of RTS patients.9 Sequence analyses have detected CREBBP mutations in another 56% of affected individuals. Schorry et al. (2008)8 evaluated genotype-phenotype correlations in 93 RTS patients and performed complete sequencing of all 31 coding regions of the CREBBP gene. The authors concluded that there were no statistically significant differences in the classic dysmorphic findings of RTS patients (e.g., typical facial aspects and broad thumbs and toes) with and without CREBBP mutations. Mutations in EP300 have been identified in 3% of RTS patients.7,9 RTS typically occurs as a de novo mutation in a family.2 Most individuals represent simplex cases (i.e., the only affected member in a family); in most instances, the parents of an individual with RTS are not affected.2,4 In this case, the empiric recurrence risk for siblings is approximately 0.1%. Although individuals with RTS rarely reproduce, the theoretical risk for the offspring is 50%.2 Prenatal testing for at-risk pregnancies is possible if the disease-causing CREBBP mutation or deletion in the family is known.7

Fetal hypoxygenation due to the anemia may be an important factor in stimulating the maturation processes of the immune system in the fetus, determining the switch from fetal to adult form. We performed an immunological evaluation in a fetus in the 29th week of gestation with secondary hypoxemia and RhD and C alloimmune anemia. We found normal relative values for total T, TCD4+ and TCD8+, and low levels of B memory and NK cells. NKT cells were absent. There IL-8 serum levels were higher than those of the mother. Fetal anemia was not capable of activating the humoral immune response and differentiation of memory B cells. Our data suggest that NKT cell differentiation may be related to thymus development in humans.

e16612Background: Cancers are increasing with aging and thus the number of elderly cancer patient is expected to increase significantly in years to come. The aims were to evaluate the cellular immune profiling associated with prostate cancer in elderly patients. Methods: We prospectively enrolled patients, who were treated and followed-up in the department geriatric clinicaloncology. Between 2015 and 2016, a prospective cohort study in 346 elderly incident cancer patients ( ≥ 60 years) , at the time of enrollment, assessed and collected socio-demographic and clinical variables and collected peripheral blood analysis in Experimental translational exploratory study. using PBMC were stained with following antibodies: anti-CD4, anti-CD8, anti-CD28, anti-CD20, anti-CD16, anti-CD56 and analyzed by four-color flow cytometry on a FACS Verse BD Bioscience. We analyzed the immune profiling of elderly patients with prostate cancer and non-cancer ( > 65). Results: We enrolled 38 patients with prostate cancer and the ...

10046Background: the elderly cancer is a heterogeneous and growing group. In the elderly, the genes of toll-like receptors (TRL) has been described as related to immunosenescence process, carcinoge...

Genomic aberrations in the CREBBP (CREB-binding protein - CREBBP or CBP) gene such as point mutations, small insertions or exonic copy number changes are usually associated with Rubinstein-Taybi syndrome (RTs). In this study, the disruption of the CREBBP gene on chromosome 16p13.3, as revealed by CGH-array and FISH, suggests immune dysregulation in a patient with the Rubinstein Taybi syndrome (RTs) phenotype. Further investigation with Western blot techniques demonstrated decreased expression of CREB, NFκB, c-Jun, c-Fos, BCL2 and cMyc in peripheral blood mononuclear cells, thus indicating that the CREBBP gene is essential for the normal expression of these proteins and the regulation of immune responses.

Rubinstein-Taybi syndrome (RTS) is a rare developmental disorder characterized by craniofacial dysmorphisms, broad thumbs and toes, mental and growth deficiency, and recurrent respiratory infections. RTS has been associated with CREBBP gene mutations, but EP300 gene mutations have recently been reported in 6 individuals. In the present study, the humoral immune response in 16 RTS patients with recurrent respiratory infections of possible bacterial etiology was evaluated. No significant differences between patients and 16 healthy controls were detected to explain the high susceptibility to respiratory infections: normal or elevated serum immunoglobulin levels, normal salivary IgA levels, and a good antibody response to both polysaccharide and protein antigens were observed. However, most patients presented high serum IgM levels, a high number of total B cell and B subsets, and also high percentiles of apoptosis, suggesting that they could present B dysregulation. The CREBBP/p300 family gene is extremely important for B-cell regulation, and RTS may represent an interesting human model for studying the molecular mechanisms involved in B-cell development.

133 Background: the elderly cancer group is a heterogeneous and growing one. In the elderly, the genes of toll-like receptors (TLR) have been described as related to the immunosenescence process and carcinogenesis. The relationship of this gene family with carcinogenesis and immunoregulatory responses seems a promising field. Methods: Between 2015 and 2016, a prospective cohort study in 445 elderly patients with incident cancer ( ≥ 60 years) at the time of admission, assessed and collected sociodemographic and clinical variables and collected analysis of peripheral blood in translational exploratory study. Determination of TLR2 and TLR9 was performed by flow cytometry with monoclonal antibodies anti-TLR2 and TLR9 in the peripheral blood at the beginning of anti-cancer therapy in older patients with cancer. Results: 445 elderly patients were included with incident cancer, age of 71.13 years (SD 7.41) means. Most were male (50.9%) and self-reported black or brown skin color (71.4%). The topography of prostate cancer was more frequent (29.4%), followed by the digestive system (24.3%). They were mostly patients with advanced stage (III and IV) at nutritional risk (52.6%) and reported using up to 5 medications (77.2%). Patients were followed for an average of 128 days (SD 54.37). During this period, there were 62 deaths (13.9 %) with a mean overall survival of 165 days (95% CI 161.25 to 170.02). There are significant differences in the percentage values of TLR9 (p = 0.0009) and TLR2 (p = 0.04) in monocytes between the groups of patients who died in less than 6 months of treatment and those who survived. Conclusions: Overexpression of TLR9 and TLR2 may be a protective factor for the occurrence of early death in elderly patients with cancer.