scholarly journals Oral Immunization With Plant-Based Vaccine Induces a Protective Response Against Infectious Bursal Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
María Soledad Lucero ◽  
Silvina Chimeno Zoth ◽  
Juan Jaton ◽  
María José Gravisaco ◽  
Silvina Pinto ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Vaccine Candidate ◽  
Protective Immune Response ◽  
Infectious Bursal Disease ◽  
Cell Infiltration ◽  
Economic Losses ◽  
Poultry Industry ◽  
T Cell Infiltration ◽  
Bursal Disease

Infectious bursal disease virus (IBDV) is the etiological agent of an immunosuppressive and highly contagious disease that affects young birds causing important economic losses in the poultry industry worldwide. We have previously developed a plant-based vaccine candidate for infectious bursal disease (IBD) that is able to protect against infection with IBDV when administered through intramuscular (im) route. Given that oral vaccination is non-invasive and stimulates the immunity of the mucosal gastrointestinal surface, the initial site of contact and entry of IBDV, the aim of this work was to study if our immunogen was also able to elicit a protective immune response when orally administered. We demonstrated that 85% of the animals that received two oral doses of the vaccine formulation and all animals that were orally boosted after an im prime scheme developed virus neutralizing antibodies and were protected against IBDV infection, evidenced by the bursa/body weight (BB) ratio, absence of T-cell infiltration, and low viral load in bursa. Although mild to moderate bursal damage was observed in some of these animals, these lesions were not as severe as the ones observed in challenged control groups, which also presented signs of acute inflammation, bursal atrophy, T-cell infiltration, and absence of viral clearance. These results show that two immunizations with our recombinant immunogen are able to induce a specific and protective immune response in chicken against IBDV when orally administered in a prime/boost scheme or when the oral boost follows an im prime scheme. In conclusion, our oral plant-based vaccine candidate could represent a viable alternative to conventional vaccines and is of great interest to the poultry industry.

scholarly journals Modelling the interplay between the CD4$$^{+}$$/CD8$$^{+}$$ T-cell ratio and the expression of MHC-I in tumours

2021 ◽  
Vol 83 (1) ◽  
Author(s):  
Christian John Hurry ◽  
Alexander Mozeika ◽  
Alessia Annibale
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Critical Level ◽  
Cell Infiltration ◽  
Cytotoxic T Cell ◽  
Mhc I ◽  
Cell Ratio ◽  
T Cell Infiltration ◽  
Immunological Mechanisms ◽  
Tcr Repertoire

AbstractDescribing the anti-tumour immune response as a series of cellular kinetic reactions from known immunological mechanisms, we create a mathematical model that shows the CD4$$^{+}$$ + /CD8$$^{+}$$ + T-cell ratio, T-cell infiltration and the expression of MHC-I to be interacting factors in tumour elimination. Methods from dynamical systems theory and non-equilibrium statistical mechanics are used to model the T-cell dependent anti-tumour immune response. Our model predicts a critical level of MHC-I expression which determines whether or not the tumour escapes the immune response. This critical level of MHC-I depends on the helper/cytotoxic T-cell ratio. However, our model also suggests that the immune system is robust against small changes in this ratio. We also find that T-cell infiltration and the specificity of the intra-tumour TCR repertoire will affect the critical MHC-I expression. Our work suggests that the functional form of the time evolution of MHC-I expression may explain the qualitative behaviour of tumour growth seen in patients.

scholarly journals ACSL4 Expression Is Associated With CD8+ T Cell Infiltration and Immune Response in Bladder Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Wenjie Luo ◽  
Jin Wang ◽  
Xiaoyan Dai ◽  
Hailiang Zhang ◽  
Yuanyuan Qu ◽  
...  
Keyword(s):  
Immune Response ◽  
Bladder Cancer ◽  
T Cell ◽  
Immune Checkpoint ◽  
Cd8 T Cell ◽  
Expression Level ◽  
Cell Infiltration ◽  
Tumor Infiltration ◽  
T Cell Infiltration ◽  
Checkpoint Genes

ObjectiveThis study aimed to explore the role of ACSL4 in CD8+ T cell tumor infiltration and outcomes of bladder cancer (BLCA) patients after immunotherapy.MethodsThe correlation between ACSL4 expression and tumor infiltration of immune cells was analyzed using the Tumor Immune Estimation Resource database. The prognostic significance of ACSL4 in BLCA was analyzed using Kaplan–Meier curves. Immunohistochemistry was used to detect CD8+ T cell infiltration in tumors with high and low ACSL4 expression obtained from patients at the Fudan University Shanghai Cancer Center. The relationships between immune checkpoint genes and immune response were analyzed using The Cancer Genome Atlas and IMvigor 210 cohorts. The molecular functions, cellular components, and biological processes involving ACSL4 were explored using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment pathway analyses.ResultsThe expression level of ACSL4 was significantly correlated with the infiltration of CD8+ T cells in BLCA tumors (r = 0.192, P = 2.22e-04). Elevated ACSL4 was associated with suppressed tumor progression and better outcomes for BLCA patients. The higher expression level of ACSL4 predicted better immunotherapeutic responses and was associated with higher expression levels of core immune checkpoint genes, including CD274, CTLA4, PDCD1, and LAG3, compared with the low ACSL4 expression group.ConclusionThis study demonstrated for the first time that elevated ACSL4 correlated significantly with CD8+ T cell infiltration and contributed to better immunotherapeutic responses in BLCA patients. Furthermore, ACSL4 serves as a novel biomarker for predicting patient outcomes after immunotherapeutic treatments, which may improve the development of individualized immunotherapy for BLCA.

scholarly journals Brain Toxoplasmosis Comorbid with Autoimmune Disease: Complicated Immune Response And Case Demonstration

2021 ◽  
Vol 48 (s2) ◽  
pp. S8-S8
Author(s):  
Alice Graham ◽  
Crystal Fong ◽  
Asghar Naqvi ◽  
Jian-Qiang Lu
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Incidental Finding ◽  
Cell Infiltration ◽  
List Type ◽  
Pathological Features ◽  
T Cell Infiltration

Toxoplasmosis is an opportunistic infection caused by Toxoplasma gondii (TG), commonly involving the brain. Symptomatic clinical disease of TG infection is much more commonly associated with immunodeficiency; clinicopathological manifestations of brain toxoplasmosis are linked to individual immune responses including brain infiltration of T-cells that are thought to fight against toxoplasmosis. In patients with autoimmune diseases, immune status is typically characterized by T-cell infiltration and complicated mainly by immunosuppressant and/or immunomodulatory treatment. In this study, we demonstrate clinical and radiological features correlated with pathological features of brain toxoplasmosis at different disease stages in a patient with coexisting autoimmune diseases, including systemic lupus erythematosus and autoimmune hepatitis. The infiltration of CD8+ T-cells in toxoplasma immunostaining-positive acute lesions was greater than that in toxoplasma immunostaining-negative chronic lesions. We also review previously reported cases of brain toxoplasmosis with comorbid autoimmune diseases. Our present case and literature review suggest that brain toxoplasmosis in patients with autoimmune diseases may be asymptomatic unless disease complications occur; it may present as an incidental finding at postmortem examination of rapidly developed lesions. T-cell infiltration in patients with autoimmune diseases and coexisting toxoplasmosis may be at least partially reduced; ultimately, the roles of T-cell infiltration in brain toxoplasmosis deserve further investigation.Learning ObjectivesDiscuss complicated immune response to toxoplasmosis in patients with autoimmune diseases.Describe clinical, radiological, and pathological features of brain toxoplasmosis in patients with autoimmune diseases.

scholarly journals Modelling the interplay between the CD4+/CD8+ T-cell ratio and the expression of MHC-I in tumours

2020 ◽  
Author(s):  
Christian John Hurry ◽  
Alexander Mozeika ◽  
Alessia Annibale
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Critical Level ◽  
Cell Infiltration ◽  
Cytotoxic T Cell ◽  
Mhc I ◽  
Cell Ratio ◽  
T Cell Infiltration ◽  
Immunological Mechanisms ◽  
Tcr Repertoire

AbstractDescribing the anti-tumour immune response as a series of cellular kinetic reactions from known immunological mechanisms, we create a mathematical model that shows the CD4+/CD8+ T-cell ratio, T-cell infiltration and the expression of MHC-I to be interacting factors in tumour elimination. Methods from dynamical systems theory and non-equilibrium statistical mechanics are used to model the T-cell dependent anti-tumour immune response. Our model predicts a critical level of MHC-I expression which determines whether or not the tumour escapes the immune response. This critical level of MHC-I depends on the helper/cytotoxic T-cell ratio. However, our model also suggests that the immune system is robust against small changes in this ratio. We also find that T-cell infiltration and the specificity of the intra-tumour TCR repertoire will affect the critical MHC-I expression. Our work suggests that the functional form of the time evolution of MHC-I expression may explain the qualitative behaviour of tumour growth seen in patients.Mathematics Subject Classification (2010)MSC 37C25 · MSC 82C99 · MSC 37N25 · MSC 92B99

scholarly journals Characterizing the tumor microenvironment of metastatic ovarian cancer by single cell transcriptomics

2020 ◽  
Author(s):  
Susan Olalekan ◽  
Bingqing Xie ◽  
Rebecca Back ◽  
Heather Eckart ◽  
Anindita Basu
Keyword(s):  
Ovarian Cancer ◽  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Single Cell ◽  
Cell Population ◽  
Cell Infiltration ◽  
T Cell Infiltration ◽  
Transcriptional State ◽  
Target Cancer

AbstractEpithelial ovarian cancer is a highly heterogenous, metastatic and lethal disease. The presence of CD8+T cells within ovarian tumors is positively associated with overall patient survival. Determining if a patient has T cells that respond to immunotherapies, their characteristics and how they can be manipulated to target cancer cells is an area of intense investigation in cancer therapy. This study determines the cellular composition and the transcriptional state of immune cells in metastatic ovarian cancer samples from patients using single cell RNA sequencing (scRNA-seq). Hierarchical clustering stratified our patient cohort into 2 main groups: 1) a high T cell infiltration (high Tinf) group and 2) a low T cell infiltration (low Tinf) group. To assess the immune response in these patient samples, we performed an unsupervised clustering of the T cell population in each group. The T cell population clustered into 4 and 3 subpopulations in the high Tinf T cell and low Tinf respectively. A granulysin expressing T cell cluster was identified and unique to the High Tinf group. Interestingly, although both groups had resident memory CD8+T (CD8+Trm) cells, only the CD8+Trm cells in the high Tinf group expressed TOX, a recently described transcription factor. TOX confers longevity to T cells within immunosuppressive environment such as cancer. Interestingly, along with TOX+ T cells, we found a unique plasmablast cluster and an IRF8+ macrophage cluster unique to the high Tinf group. Our comprehensive scRNA-seq study provides important insights in elucidating the immune response in ovarian cancer patients.

scholarly journals High Stroma T-Cell Infiltration is Associated with Better Survival in Stage pT1 Bladder Cancer

2020 ◽  
Vol 21 (21) ◽  
pp. 8407
Author(s):  
Sabine Hülsen ◽  
Eleonora Lippolis ◽  
Fulvia Ferrazzi ◽  
Wolfgang Otto ◽  
Luitpold Distel ◽  
...  
Keyword(s):  
Immune Response ◽  
Bladder Cancer ◽  
T Cell ◽  
Immune Cell ◽  
Negative Impact ◽  
Cell Infiltration ◽  
T Cell Infiltration ◽  
Tertiary Lymphoid Structures ◽  
Lymphoid Structures

Stage pT1 bladder cancer (BC) shows highly diverse outcomes. Predictive markers are required to stratify patients for personalized treatment. The present study aimed to validate immune response quantification as a prognostic marker. Patients with pT1 BC (n = 167) treated by transurethral resection of the bladder (TURB) were enrolled. Formaldehyde-fixed paraffin-embedded material was stained for CD3 and CD8. Corresponding T cells were counted in three regions with the highest immune response. Numbers of tertiary lymphoid structures (TLS) and lymphocyte aggregates (LA) were quantified. High CD3+ stroma T-cell infiltration was associated with improved survival (p = 0.045), especially in the G3 subgroup (p = 0.01). Cluster with higher immune response showed less recurrence (p = 0.034) and favorable overall survival (OS) (p = 0.019). In contrast, higher CD3+ and CD8+ tumor T-cell infiltration seemed to have a negative impact on prognosis. TLS and LA were more frequently observed in G3 tumors, indicating an increased anti-tumoral immune response. We proved the role of immune cell infiltration and showed that higher infiltration numbers of CD3+ (not CD8+) lymphocytes in the stroma are associated with favorable outcome. Immune cell quantification could be used as a marker to help stratify patients’ risk and therefore, to optimize patients’ management and follow-up examination as well as possible therapies.

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