(1) Background: No information is available on how dogs with hypothyroidism (HypoT) respond to vaccination. This study measured pre- and post-vaccination anti-canine parvovirus (CPV) antibodies in dogs with HypoT treated with levothyroxine and compared the results to those of healthy dogs. (2) Methods: Six dogs with HypoT and healthy age-matched control dogs (n = 23) were vaccinated against CPV with a modified-live vaccine. Hemagglutination inhibition was used to measure antibodies on days 0, 7, and 28. The comparison of the vaccination response of dogs with HypoT and healthy dogs were performed with univariate analysis. (3) Results: Pre-vaccination antibodies (≥10) were detected in 100% of dogs with HypoT (6/6; 95% CI: 55.7–100) and in 100% of healthy dogs (23/23; 95% CI: 83.1–100.0). A ≥4-fold titer increase was observed in none of the dogs with HypoT and in 4.3% of the healthy dogs (1/23; CI95%: <0.01–22.7). Mild vaccine-associated adverse events (VAAEs) were detected in 33.3% of the dogs with HypoT (2/6; 95% CI: 9.3–70.4) and in 43.5% (10/23; 95% CI: 25.6–63.2) of the healthy dogs. (4) Conclusions: There was neither a significant difference in the dogs’ pre-vaccination antibodies (p = 1.000), or vaccination response (p = 0.735), nor in the occurrence of post-vaccination VAAEs (p = 0.798). The vaccination response in dogs with levothyroxine-treated HypoT seems to be similar to that of healthy dogs.

It is unknown how dogs with hyperadrenocorticism (HAC) respond to vaccination. This study measured antibodies against canine parvovirus (CPV) in dogs with HAC treated with trilostane before and after CPV vaccination, and compared the immune response to that from healthy dogs. Eleven dogs with HAC, and healthy age-matched control dogs (n = 31) received a modified-live CPV vaccine. Antibodies were determined on days 0, 7, and 28 by hemagglutination inhibition. Univariate analysis was used to compare the immune response of dogs with HAC and healthy dogs. Pre-vaccination antibodies (≥10) were detected in 100% of dogs with HAC (11/11; 95% CI: 70.0–100) and in 93.5% of healthy dogs (29/31; 95% CI: 78.3–99.2). No ≥4-fold increase in antibody titer was observed in dogs with HAC while in 22.6% of healthy dogs, a ≥4-fold titer increase was observed (7/31; 95% CI: 11.1–40.1). Mild vaccine-associated adverse events (VAAEs) were detected in 54.5% of dogs with HAC (6/11; 95% CI: 28.0–78.8) and in 29.0% of healthy dogs (9/31; 95% CI: 15.9–46.8). There was neither a significant difference in presence of pre-vaccination antibodies (p = 1.000), or response to vaccination (p = 0.161), nor in the occurrence of VAAEs (p = 0.158). Immune function of dogs with HAC treated with trilostane seems comparable to that of healthy dogs.

The high susceptibility to infection in persons with Down Syndrome (DS) has led some investigators to explore the possibility of a defect in the immune system. Studies to date indicate no defect in humoral immunity suggesting that the defect might be in the cellular immune functions, but no specific defect has been found. Our investigation of the cellular immune system of adult DS patients was conducted by examining (1) the number and function of T-lymphocytes, (2) the phagocytic function of granulocytes, (3) the level of superoxide dismutase-1 (SOD-1) in leukocytes, and (4) the effects of SOD-1 on lymphocyte and granulocyte functions.

Background: The mechanisms through which immunosuppressed patients bear increased risk and worse survival in oral squamous cell carcinoma (OSCC) are unclear. Here, we used deep learning to investigate the genetic mechanisms underlying immunosuppression in the survival of OSCC patients, especially from the aspect of various survival-related subtypes. Materials and methods: OSCC samples data were obtained from The Cancer Genome Atlas (TCGA), International Cancer Genome Consortium (ICGC), and OSCCrelated genetic datasets with survival data in the National Center for Biotechnology Information (NCBI). Immunosuppression genes (ISGs) were obtained from the HisgAtlas and DisGeNET databases. Survival analyses were performed to identify the ISGs with significant prognostic values in OSCC. A deep learning (DL)-based model was established for robustly differentiating the survival subpopulations of OSCC samples. In order to understand the characteristics of the different survival-risk subtypes of OSCC samples, differential expression analysis and functional enrichment analysis were performed. Results: A total of 317 OSCC samples were divided into one inferring cohort (TCGA) and four confirmation cohorts (ICGC set, GSE41613, GSE42743, and GSE75538). Eleven ISGs (i.e., BGLAP, CALCA, CTLA4, CXCL8, FGFR3, HPRT1, IL22, ORMDL3, TLR3, SPHK1, and INHBB) showed prognostic value in OSCC. The DL-based model provided two optimal subgroups of TCGA-OSCC samples with significant differences (p = 4.91E-22) and good model fitness [concordance index (C-index) = 0.77]. The DL model was validated by using four external confirmation cohorts: ICGC cohort (n = 40, C-index = 0.39), GSE41613 dataset (n = 97, C-index = 0.86), GSE42743 dataset (n = 71, C-index = 0.87), and GSE75538 dataset (n = 14, C-index = 0.48). Importantly, subtype Sub1 demonstrated a lower probability of survival and thus a more aggressive nature compared with subtype Sub2. ISGs in subtype Sub1 were enriched in the tumorinfiltrating immune cells-related pathways and cancer progression-related pathways, while those in subtype Sub2 were enriched in the metabolism-related pathways. Conclusion: The two survival subtypes of OSCC identified by deep learning can benefit clinical practitioners to divide immunocompromised patients with oral cancer into two subpopulations and give them target drugs and thus might be helpful for improving the survival of these patients and providing novel therapeutic strategies in the precision medicine area.

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<p> Although immune checkpoint inhibitors block one mechanism of regulatory T cell (Treg) immunosuppression, no drug has been designed to inhibit all immunosuppressive activities of Tregs. We describe here a mechanism for manipulating Treg function in a tumor microenvironment without altering their properties in healthy tissues. For this purpose, we first identify a small molecule that binds specifically to Tregs in tumors but not in healthy tissues. We then exploit this binder to deliver an attached imaging agent or an immune activator specifically into tumor-resident Tregs. Analysis of the resulting tumors demonstrates that targeting of a Toll-like receptor 7 agonist to tumor Tregs inhibits their expression of FOXP3, PD-1, CTLA4, and HELIOS, resulting in 40-80% reduction in tumor growth and repolarization of other tumor-infiltrating immune cells to more inflammatory phenotypes. Since Tregs comprise <1% of cells in the tumor masses examined, these data argue that Tregs exert a disproportionately large effect on tumor immunity. The data also demonstrate that the immunosuppressive properties of Tregs can be manipulated without altering their properties in healthy tissues.</p>

Alterations of immune parameters were investigated in fish exposed to non-overtly toxic levels of three different environmentally relevant chemicals, 7,12-dimethylbenzanthracene (DMBA), hexachlorocyclohexane (lindane), and 2,3,7,8- tetrachlorodibenzo-p -dioxin (TCDD). Each chemical agent was administered to tilapia in separate experiments by intraperitoneal injection for five consecutive days. Following the final dose, total cellularity and histology of the spleen and pronephros were assessed, as were activity of phagocytic celis contained in these hematopoietic organs. <p>Using chemical doses which produced no clinical toxicity, tilapia exposed to each chemical agent displayed a significant reduction in total cell number of both spleen and pronephros, in most cases in a dose-related manner. Consistent with this observation, splenic and pronephric hypocellularity was confirmed upon histological examination of chemical-treated fish. However, neither superoxide radical production or phagocytosis of splenic or pronephric macrophages was inhibited in either DMBA, lindane, or TCDD exposed fish. Results of this study indicate that depressed total cell number in fish hematopoietic organs may be a more sensitive indicator of exposure to these environmental contaminants than is the activity of macrophages contained within these organs. / Master of Science

Cyclosporine and prednisone are immunosuppressive drugs that are commonly used in combination for the treatment of immune-mediated diseases, and have been shown to individually cause significant suppression of IL-2. Currently, no studies have been performed to determine how a combination of the two drugs would impact suppression of IL-2, and if an additive or synergistic effect on cytokine production could be demonstrated, as in studies of other species. An additive effect of immunosuppression associated with this drug combination could allow clinicians to decrease dosages of drugs, thereby reducing drug costs and minimizing adverse drug side effects. In a cross-over study design using six healthy dogs, the expression of IL-2 was affected with administration of cyclosporine, prednisone, or a combination of each drug. However, there was no significant difference in the level of immunosuppression compared to cyclosporine alone. Small sample size and the dosages of each drug used potentially affected the strength of the results.