Clinical and immunological allergy assessment in cancer patients

Cancer is associated with immunodeficiency, while allergies result from immune system hyperactivity mediated by cytokines and immunoglobulins. The purpose of this study was to determine the relationship between immune environment of specific cancers and allergies, emphasizing cytokines related to Th1 and Th2 responses associated with IgE. 80 adults were distributed into two groups: control (n = 20) and cancer (n = 60), distributed in three subgroups (n = 20), head and neck, stomach, and prostate cancers. This study compared Th1 (IL-2) and Th2 (IL-4) parameters, anti-inflammatory, pro-inflammatory, or regulatory profile regarding both IgE levels and reported allergies, by means of clinical manifestations and IgE, IL-1β, IL-2, IL-4, IL-17, and TGF-β serum concentration. Clinically allergies were observed in 50% of the control group and in 20% of the cancer group (p = 0.009). IL-2 cytokine and TGF-β concentrations were higher in the patients with cancer as compared to the control (p < 0.005). However, there were IL-4, IL-17, and IL-1β decreases in the patients with cancer (p < 0.05). No correlation was observed between the cytokines studied and IgE and clinically proven allergies in both investigated groups. There was an inverse association between cancer and clinical allergy manifestations. In head and neck, stomach, and prostate cancers, an immunosuppressive serum tumor environment was predominant. There was no difference in cytokines related to Th1 and Th2 parameters in relation to IgE. No correlation was found between clinically proved allergies and immunity markers related to the same allergens.

Evaluation of Cellular Immune Responses in Dogs Immunized with Alum-Precipitated Autoclaved Leishmania major along with BCG and Imiquimod

Background: We aimed to investigate the potential effects of BCG and imiquimod on improvement of current experimental L. major vaccine against dogs in an endemic area of Zoonotic visceral leishmaniasis (ZVL) in Iran. Methods: During 2012 till 2014, seven mixedbreed shepherd dogs with no anti-Leishmania antibodies and no response to Leishmanin reagent were immunized with 2 doses of alum-precipitated autoclaved L. major (Alum-AML) while BCG and imiquimod (for skin pre-treatment) were used as adjuvants. The productions of a few characteristic cytokines of T-helper immune responses and the development of delayed-type hypersensitivity (DTH) of the immunized animals were then evaluated, up to 300 days. Blood samples were collected at 0, 30, 80 and 300 d post-vaccination and the concentrations of IFN-γ, IL10, IL-12 and TGF-β cytokines secreted from PBMCs at these time-points were quantified by ELISA. DTH was evaluated by Leishmanin skin test (LST). Results: Although a similar LST conversion was observed at all time-points, the cytokine measurement results indicated significantly higher levels of IFN-γ at day 80 and elevated levels of IL-10 at days 80 and 300, post-vaccination. Moreover, a significantly higher IFN-γ/IL-10 ratio was observed at day 30 post-vaccination compared to the other time-points. Conclusion: Although a Th1-like response could be observed at day 30 post-vaccination, the development of cytokine profiles was inclined toward mixed Th1 and Th2 responses at days 80 and 300 post-vaccination. This situation may indicate the requirement of an additional boosting by this Alum-AML formula, in order to induce long-lasting protection against ZVL.

Post-Coronavirus Era: Should We Expect a Surge in Allergic Diseases and Asthma?

Some infectious agents by priming the immune system promote protection against allergy and asthma. During infections, Th1 immune responses are dominant, while in allergic conditions, Th2 responses are more pronounced. Th1 immune response protects the body against infections, and Th2 response leads to allergy and asthma. For maintaining health, the balance between Th1 and Th2 responses is necessary. The COVID-19 infection augments Th1 and also eosinophilic responses. On the other hand, the main protocols to control the COVID-19 pandemic require adherence to health standards, maintaining personal hygiene, frequent disinfecting of hands, using face masks, etc. In the post-COVID-19 era, this sterile condition may relinquish, and the Th1/Th2 immune imbalance may lead to an increase in the incidence of allergy and asthma. Therefore, focus on the COVID-19 infection should not deter us from foreseeing a surge in asthma and other post-coronavirus problems.

Decreased Expression of T-Cell-Associated Immune Markers Predicts Poor Prognosis in Patients with Advanced Follicular Lymphoma Received Rituximab Plus Bendamustine

Background: Several clinical risk stratification models have been proposed to predict the clinical outcomes of follicular lymphoma (FL) cases, however, few reports are available to predict prognosis of FL cases receiving bendamustine-based regimens. We previously examined the utility of rituximab-bendamustine (RB) treatment for newly diagnosed advanced FL, who showed non-optimal responses to two cycles of R-CHOP therapy. Methods: In this study, we explored the biomarkers that could influence outcomes for the RB-treated FL cases in the context of the prospective cohort by target capture and sanger sequencing, and gene-expression profiling analyses using 50 diagnostic biopsies.Results: We first examined the mutational status of 410 genes in tumor specimens derived from RB-treated cases. As reported before, CREBBP, KMT2D, MEF2B, BCL2, EZH2, CARD11, TNFRSF14, EP300, and APC were recurrently mutated, however, none of which was predictive for progression-free survival (PFS) in RB-treated cases. Similarly, the m7-FLIPI did not correlate with PFS or progression of disease within 24 months (POD24). A gene expression analysis using a panel of 770 genes associated with carcinogenesis and/or immune response showed that the expression of CD8+ T-cell markers (GZMM, FLT3LG, CD8A, CD8B, GZMK) and half of the genes regulating Th1 and Th2 responses were significantly lower in the POD24 group than in the noPOD24 group. Finally, we selected 10 genes (TBX21, CXCR3, CCR4, CD8A, CD8B, GZMM, FLT3LG, CD3E, EOMES, GZMK), and dichotomized RB-treated cases into immune infiltrationhigh (infilhigh) and infiltrationlow (infillow) clusters. The 3-years PFS rate was lower in the infillow cluster than in the infilhigh cluster (50.0% [95% CI: 27.1–69.2%] vs. 84.2% [95% CI: 58.7–94.6%], p=0.0237). Of note, the proportion of cases with peripheral lymphopenia (<869/mL) at diagnosis was higher in the infillow cluster than in the infilhigh cluster (38.5% vs. 9.09%, OR: 6.25 [95%CI, 1.20-32.7], p=0.0235). Conclusion: These results suggest that the T-cell-associated immune markers could be useful to predict prognosis in RB-treated FL cases.Trial registration: This trial was retrospectively registered in UMIN on April. 24, 2014 (UMIN000013795; http://www.umin.ac.jp/icdr/index-j.html).

Clinical and immunological allergy assessment in cancer patients.

e15021 Background: Cancer is associated with immunodeficiency, while allergies result from immune system hyperactivity mediated by cytokines and immunoglobulins. The purpose of this study was to determine the relationship between immune environment of specific cancers and allergies, emphasizing cytokines related to Th1 and Th2 responses associated with IgE. Methods: 80 adults were distributed into two groups: control (n = 20) and cancer (n = 60), distributed in three subgroups (n = 20), head and neck, stomach, and prostate cancers. This study considered cytokine deviation in Th1 (IL-2) response to Th2 (IL-4), anti-inflammatory, pro-inflammatory, or regulatory profile regarding both IgE levels and reported allergies, by means of clinical manifestations and IgE, IL-1β, IL-2, IL-4, IL-17, and TGF-β serum concentration. Results: Clinically allergies were observed in 50% of the control group and in 20% of the cancer group (p = 0.01). IL-2 cytokine and TGF-β concentrations were higher in the patients with cancer as compared to the control (p < 0.005). However, there were IL-4, IL-17, and IL-1β decreases in the patients with cancer (p < 0.05). No correlation was observed between the cytokines studied and IgE and clinically proven allergies in both investigated groups. Conclusions: There was an inverse association between cancer and clinical allergy manifestations. In head and neck, stomach, and prostate cancers, an immunosuppressive serum tumor environment was predominant. Cytokine deviation in the Th1 response to Th2 in relation to IgE was not identified. No correlation was found between clinically proved allergies and immunity markers related to the same allergens.

Functionally distinct T-helper cell phenotypes predict resistance to different types of parasites in a wild mammal

1. The adaptive immune system is critical to an effective, long-lasting ability to respond to infection in vertebrates and T-helper (Th) cells play a key role in orchestrating the adaptive immune response. Laboratory studies show that functionally distinct Th responses provide protection against different kinds of parasites (i.e., Th1 responses against microparasites and Th2 against macroparasites). 2. Natural populations must deal with challenges from a wide range of infectious agents and co-infection with different types of parasite is the norm, so different Th responses are likely to play an important and dynamic role in maintaining host health and fitness. However, the relationship between T helper immune phenotypes and infection with different types of parasites remains poorly understood in wild animals. 3. In this study, we characterised variation in functionally distinct Th responses (Th1, Th2, Th17 and regulatory responses) in a wild population of Soay sheep using flow cytometry to detect Th-subset specific transcription factors, and ex vivo lymphocyte stimulation to quantify release of Th-associated cytokines. We specifically tested the prediction that raised Th1 and Th2 responses should predict reduced apicomplexan (coccidian) and helminth (nematode) parasite burdens, respectively. 4. Cell counts of different Th subsets measured by flow cytometry did not vary with age or sex. However, all measures of Th-associated ex vivo cytokine production increased with age, and Th17- and regulatory Th-associated cytokine production increased more rapidly with age in males than females. 5. Independent of age and sex, Th2-associated immune measures negatively predicted gastro-intestinal strongyle nematode faecal egg count, while production of the Th1-associated cytokine IFN-γ negatively predicted coccidian faecal oocyst count. 6. Our results provide important support from outside the laboratory that Th1 and Th2 responses confer resistance to different kinds of parasites (micro- and macro-parasites, respectively). They also add to mounting evidence from wild populations that Th1/Th2 trade-offs often observed in controlled laboratory experiments may not readily translate to more complex natural systems. 7. Our study illustrates that harnessing more specific reagents and tools from laboratory immunology has the potential to illuminate our understanding of epidemiology and host-parasite co-evolution in the wild.

Comparison of the efficacy of HIV-1 Nef-Tat-Gp160-p24 polyepitope vaccine candidate with Nef protein in different immunization strategies

Objectives: One of the promising strategies for effective HIV-1 vaccine design involves finding the polyepitope immunogens using T cell epitopes. Methods: Herein, an HIV-1 polyepitope construct (i.e., Nef-Tat-Gp160-P24) comprising of several epitopes from Nef, Tat, Gp160, and P24 proteins was designed. To improve its immunogenicity in BALB/c mice, cell-penetrating peptides (HR9 & MPG for DNA delivery, and LDP-NLS & CyLoP-1 for protein transfer), Montanide adjuvant, and heterologous DNA prime/polypeptide boost strategy were used. To compare the immunogenicity, Nef was utilized as a vaccine candidate. The levels of total IgG and its subclasses, cytokines, and Granzyme B were assessed using ELISA. Results: Immunological studies showed that heterologous prime-boost regimens for both antigens could considerably augment the levels of IgG2a, IgG2b, IFN-γ, and Granzyme B directed toward Th1 and CTL immune responses in comparison with homologous prime-boost strategies. The levels of IFN-γ, IL-10, total IgG, IgG1, and IgG2b were drastically higher in groups immunized with Nef-Tat-Gp160-P24 in heterologous prime-boost regimens than those in groups immunized with Nef. Conclusions: The use of the Nef-Tat-Gp160-P24 polyepitope immunogen in heterologous prime-boost strategy could generate the mixture of Th1 and Th2 responses directed further toward Th1 response as a hopeful method for improvement of HIV-1 vaccine.

Immunomodulatory Effects of Rhinovirus and Enterovirus Infections During the First Year of Life

Early childhood infections have been implicated in the development of immune-mediated diseases, such as allergies, asthma, and type 1 diabetes. We set out to investigate the immunomodulatory effects of early viral infections experienced before the age of one year on the peripheral regulatory T cell population (Treg) and circulating cytokines in a birth-cohort study of Estonian and Finnish infants. We show here a temporal association of virus infection with the expression of FOXP3 in regulatory T cells. Infants with rhinovirus infection during the preceding 30 days had a higher FOXP3 expression in Treg cells and decreased levels of several cytokines related to Th1 and Th2 responses in comparison to the children without infections. In contrast, FOXP3 expression was significantly decreased in highly activated (CD4+CD127−/loCD25+FOXP3high) regulatory T cells (TregFOXP3high) in the infants who had enterovirus infection during the preceding 30 or 60 days. After enterovirus infections, the cytokine profile showed an upregulation of Th1- and Th17-related cytokines and a decreased activation of CCL22, which is a chemokine derived from dendritic cells and associated with Th2 deviation. Our results reveal that immunoregulatory mechanisms are up-regulated after rhinovirus infections, while enterovirus infections are associated with activation of proinflammatory pathways and decreased immune regulation.

Protection and Safety Evaluation of Live Constructions Derived from the Pgm− and pPCP1− Yersinia pestis Strain

Based on a live attenuated Yersinia pestis KIM10(pCD1Ap) strain (Pgm−, pPCP1−), we attempted to engineer its lipid A species to achieve improvement of immunogenicity and safety. A mutant strain designated as YPS19(pCD1Ap), mainly synthesizing the hexa-acylated lipid A, and another mutant strain designated as YPS20(pCD1Ap), synthesizing 1-dephosphalated hexa-acylated lipid A (detoxified lipid A), presented relatively low virulence in comparison to KIM10(pCD1Ap) by intramuscular (i.m.) or subcutaneous (s.c.) administration. The i.m. administration with either the KIM10(pCD1Ap) or YPS19(pCD1Ap) strain afforded significant protection against bubonic and pneumonic plague compared to the s.c. administration, while administration with completely attenuated YPS20(pCD1Ap) strain failed to afford significant protection. Antibody analysis showed that i.m. administration induced balanced Th1 and Th2 responses but s.c. administration stimulated Th2-biased responses. Safety evaluation showed that YPS19(pCD1Ap) was relatively safer than its parent KIM10(pCD1Ap) in Hfe−/− mice manifesting iron overload in tissues, which also did not impair its protection. Therefore, the immune activity of hexa-acylated lipid A can be harnessed for rationally designing bacteria-derived vaccines.