Effect of feeding Lipopolysaccharide as an immunostimulant on immune response and immune gene expression of Labeo bata

2017 ◽  
Vol 188 ◽  
pp. 48-58 ◽  
Author(s):  
Lopamudra Sahoo ◽  
Janmejay Parhi ◽  
Chandan Debnath ◽  
Kurcheti Pani Prasad
Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5290-5290
Author(s):  
Priscilla Brito Silva ◽  
Juliana Monte Real ◽  
Ludmila Rodrigues Pinto Ferreira ◽  
Gustavo Henrique Esteves ◽  
Joao Garibaldi Junior ◽  
...  

Abstract Introduction: Interleukin (IL)-10 is an anti-inflammatory cytokine with potent inhibitory effects in immune response. Higher expression of IL-10 has also been detected in classical Hodgkin lymphoma (cHL), and it has been suggested that the cytokine is involved in the pathogenesis of these tumors. CTLA-4 has long been recognized as regulatory function, potentially decreasing antitumor immune response. Augmentation of the immune response via blockade of CTLA-4 has shown an improvement in survival for patients with metastatic melanoma, Overexpression of PD-L1 on Reed-Sternberg cells is related with downregulation of effector T cell function and represents a potent mechanism of tumor evasion. PD-L1 inhibitors have shown excellent results in refractory cHL patients. Objectives: The aim of the study was to evaluate the immune gene expression profile in peripheral blood of cHL patients at diagnosis and post-treatment and correlate these findings with clinical and epidemiological aspects. Patient and Methods: This is an open multicenter study and, so far, we included 51 patients consecutively from February 2011 to November 2015. Twenty consecutively diagnosed cHL patients, with whole blood RNA extracted at diagnosis and after treatment, were recruited for this study and prospectively evaluated. The general expression of 96 messengers RNAs present in the peripheral blood and involved in immune response was performed by a customized quantitative real-time PCR array (TaqMan¨Low Density Array). The data was normalized with B2M mRNAs levels and relative gene expression was calculated by the 2^DDCt method, considering Wilcoxon test and Benjamini-Hochberg adjustment to correct p-values. In this study, only cHL patients whose histology could be confirmed were studied. All patients were HIV negative and received ABVD chemotherapy protocol and radiotherapy if necessary. Results: From the 20 patients included in this study, 12 (60%) were male, 5 (31%) had Epstein Barr virus related cHL, 18 (90%) patients presented with B symptoms, 19 (95%) patients had advanced disease at diagnosis (stage IIBX, III and IV). Results of immune gene expression profile in paired samples from 15 patients before (pre) treatment and after (post) treatment are summarized in the following table: We observed higher expression of CD274 (PD-L1), CTLA-4 and IL-10 mRNAs in patients at diagnosis compared to expression after treatment. We found no association between relapse and immune gene expression or epidemiological and clinical characteristics. Conclusions: In this study we showed that IL-10, CD274 (PD-L1) and CTLA4 are downregulated after therapy, which suggests a mechanism for tumor immune evasion that was reverted by ABVD chemotherapy and radiotherapy. Understanding cHL associated immunosuppression and the immune reconstitution after treatment maybe the key to develop new prognostic factors and treatment strategies. Table Table. Disclosures No relevant conflicts of interest to declare.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20693-e20693
Author(s):  
Sara Baglivo ◽  
Fortunato Bianconi ◽  
Francesca Romana Tofanetti ◽  
Biagio Ricciuti ◽  
Lorenza Pistola ◽  
...  

e20693 Background: Immune checkpoint inhibitors (ICIs) have revoluzionized the therapeutic paradigm for different types of cancer including NSCLC. Clinical benefit, however, is limited to a minority of patients. The only adopted predictive biomarker, PD-L1 IHC testing, suffers from some limitations. A better understanding of biomarkers associated with response to ICIs is needed. Here, we studied immune gene expression profile and association with clinical response to immunotherapy in advanced NSCLC patients (pts) treated with ICI. Methods: A total of 37 Formalin-fixed, paraffin-embedded (FFPE) samples from advanced NSCLCs were analyzed by RNA-Seq using the Oncomine Immuno Response Assay (OIRRA) (ThermoFisher Scientific) to measure the expression level of 395 genes associated with 36 functional groups including checkpoint pathways, lymphocyte regulation and cytokine interactions, using the Ion Chef and Ion Torrent PGM. Gene level differential expression analysis were performed with the Torrent Suite and Transcriptome Analysis Console (TAC) 4.0 Software. Gene network analysis based on Bayesian algorithm was performed by GeneMANIA database querying with the genes selected through mRNA expression analysis. Results: Among 37 FFPE samples only 18 showed more than 300 OIRRA detectable target genes. In this subgroup, gene expression analysis revealed 7 genes (CCR2, CRTAM, FASLG, SELL, TIGIT, TNFRSF4, and TP63) up-regulated and one gene (CXCL8) down-regulated (p-value < 0.05) in ICI-responders compare to ICI-no responders. Bayesian enrichment computational analysis of the eight gene expression signature showed a more complex network which involves other 10 genes (SIRPG, GZMK, XCL2, CD8A, CD2, IFNG, SIT1, TAGAP, PTPRC and GZMH), correlated with different functional groups. Three main immune-pathways were identified (p < 0.01) (T cell activation, leucocyte activation and migration) involving TIGIT, TNFRSF4, CCR2 and CXCL8 genes among the gene expression signature identified. Conclusions: Our results revealed an immune response gene expression signature of 8 genes differentially expressed between ICI and ICI-no responders. Cancer systems biology analysis approach strengthen our findings identifying an immune molecular network and confirm the correlation of the gene expression signature with relevant immune regulatory functions. If validated, our results may have an important role for the development of a robust test to select patients properly and predict immune response to enable precision immunotherapy.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5294-5294
Author(s):  
Priscilla Brito Silva ◽  
Juliana Monte Real ◽  
Ludmila Rodrigues Pinto Ferreira ◽  
Gustavo Henrique Esteves ◽  
Joao Garibaldi Junior ◽  
...  

Abstract Introduction: Although immunosuppression has long been recognized in classical Hodgkin lymphoma (cHL), the underlying basis for this lack of an effective immune response against tumor remains unclear. Recently, our group showed increased frequencies levels of pro and anti-inflammatory cytokines, such as interleukins IL-6, IL-10, TNF-alpha and sCD25 in cHL patients and the impact of treatment on these cytokines. These cytokines participate in the Hodgkin and Reed-Sternberg (HRS) cells survival and immunological escape. Objectives: In this study we aimed to evaluate the immune gene expression profile in cHL patients at diagnosis and the impact of treatment on this profile. Patient and Methods: This is an open multicenter study and, so far, we included 51 patients consecutively from February 2011 to November 2015. Twenty consecutively diagnosed cHL patients, with whole blood RNA extracted at diagnosis and after treatment, were recruited for this study and prospectively evaluated. The general expression of 96 messengers RNAs present in the peripheral blood and involved in immune response was performed by a customized quantitative real-time PCR array (TaqMan¨Low Density Array). We also included 7 healthy controls. The data was normalized with B2M mRNAs levels and relative gene expression was calculated by the 2^DDCt method, considering Wilcoxon test and Benjamini-Hochberg adjustment to correct p-values. In this study, only cHL patients whose histology could be confirmed were studied. All patients were HIV negative and received ABVD chemotherapy protocol and radiotherapy if necessary. Results: From the 20 patients included for this study, 12 (60%) were male, 5 (31%) had Epstein Barr virus related cHL, 18 (90%) patients presented with B symptoms, 19 (95%) patients had advanced diseases at diagnosis (stage IIBX, III and IV) and 10% of patients relapsed. Results of immune gene expression profile in patients before (pre) treatment, after (post) treatment and healthy subjects (controls) are summarized in the following table: We observed that 4 mRNAs were altered in cHL patients before therapy (IL-10, CCL2, CD40 and HLA-DRA). After treatment, gene expression profile was similar to healthy controls. When we considered paired samples from 15 patients, 10 mRNAs were differently expressed after therapy, although the adjusted p value showed no different expression. We found no association between clinical and epidemiological characteristics with immune gene expression profile. Conclusions: In this study we showed that, in comparison with healthy donors, cHL patients presented higher expression of inflammatory genes in peripheral blood at diagnosis. After treatment, gene expression profile was comparable to healthy controls. Furthermore, treatment seems to restore a more effective immune response; particularly, IL-10, CD274 (PD-L1) and CTLA4 which were downregulated after therapy. Understanding cHL associated immunosuppression and the immune reconstitution after treatment maybe the key to develop new prognostic factors and treatment strategies. Table Table. Disclosures No relevant conflicts of interest to declare.


2007 ◽  
Vol 274 (1614) ◽  
pp. 1211-1217 ◽  
Author(s):  
Kenneth M Fedorka ◽  
Jodell E Linder ◽  
Wade Winterhalter ◽  
Daniel Promislow

Reproductive costs are an essential component of evolutionary theory. For instance, an increase in reproduction is generally coupled with a decrease in immunocompetence shortly after mating. However, recent work in Drosophila melanogaster suggests that the potential to mount an immune response, as measured by the levels of immune gene expression, increases after mating. These data are in contrast to previous studies, which suggest that mating can reduce a fly's ability to survive an actual bacterial challenge (realized immunity). This pattern may be driven by some aspect of mating, independent of resource limitation, which reduces immune function by inhibiting the effective deployment of immune gene products. Though several studies have examined both the potential and the realized immunity after mating, none have examined these immune measures simultaneously. Here, we examined the link between the potential and the realized immunity in a sterile mutant of D. melanogaster . Shortly after mating, we found that female immune gene expression was high, but survival against infection was low. Surprisingly, this pattern was reversed within 24 h. Thus, estimates of immunity based on gene expression do not appear to reflect an actual ability to defend against pathogens in the hours following copulation. We discuss the possible mechanisms that may account for this pattern.


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