Schistosomiasis treatment relies on the use of a single drug, praziquantel, which is insufficient to control transmission in highly endemic areas1. Novel medicines and vaccines are urgently needed2,3. An experimental human model for schistosomiasis could accelerate the development of these products. We performed a dose-escalating clinical safety trial in 17 volunteers with male Schistosoma mansoni cercariae, which do not produce eggs (clinicaltrials.gov NCT02755324), at the Leiden University Medical Center, the Netherlands. The primary endpoints were adverse events and infectivity. We found a dose-related increase in adverse events related to acute schistosomiasis syndrome, which occurred in 9 of 17 volunteers. Overall, 5 volunteers (all 3 of the high dose group and 2 of 11 of the medium dose group) reported severe adverse events. Worm-derived circulating anodic antigen, the biomarker of the primary infection endpoint, peaked in 82% of volunteers at 3-10 weeks following exposure. All volunteers showed IgM and IgG1 seroconversion and worm-specific cytokine production by CD4+ T cells. All volunteers were cured with praziquantel provided at 12 weeks after exposure. Infection with 20 Schistosoma mansoni cercariae led to severe adverse events in 18% of volunteers and high infection rates. This infection model paves the way for fast-track product development for treatment and prevention of schistosomiasis.

Malignant B cells in chronic lymphocytic leukemia serve an essential role in the whole immune response, so their interactions with other immune cells are more complex than observed in solid tumors. The latest study results indicate that the immune dysregulation in chronic lymphocytic leukemia (CLL) also affects a small population of invariant natural killer T cells (iNKT). Using peripheral blood iNKT cells obtained from patients with CLL, the objective of the present study was to assess the intracellular expression of typical cytokines involved in the Th1 (IFN-γ) and Th2 (IL-4) response pathways following stimulation with the iNKT-specific ligand α-galactosylceramide. iNKT cells from patients with CLL exhibited upregulated IL-4 and IFN-γ expression in comparison to those from HVs. No significant association between the ability of iNKT cells to produce IL-4 or IFN-γ and the expression of CD1d on leukemic B lymphocytes or monocytes was identified. However, the function of iNKT cells was compromised in patients with CLL by a strong Th2 bias (high IL-4 and low IFN-γ expression). The ratio of iNKT+IFN-γ+:iNKT+IL-4+ was significantly decreased in the CLL group when compared with HVs, and this decreased further as the disease progressed. This change may result in the promotion of leukemic B lymphocyte survival. Therefore, in the pathogenesis of CLL, Th2 bias may delay the antitumor response that relies on stimulation of the Th1 immune response.

Anthracycline-based chemotherapies for breast cancer are known to adversely affect patients' quality of life (QOL) and immune function. For that reason, adjuvants that improve those impairments are required. A randomized double-blind study was conducted to evaluate the effectiveness of Lentinula edodes mycelia extract (LEM), which is an oral biological response modifier (BRM) medicine for cancer patients as such an adjuvant. A total of 47 breast cancer patients who were scheduled to receive postoperative adjuvant anthracycline-based chemotherapy, i.e., 5-fluorouracil (5-FU) + cyclophosphamide + epirubicin (FEC regimen), 5-FU + cyclophosphamide + doxorubicin/pirarubicin (FAC regimen), cyclophosphamide + doxorubicin/pirarubicin (AC regimen) and cyclophosphamide + epirubicin (EC regimen), were entered in the study. The patients were randomly divided into either an LEM or a placebo tablet group; the tablets were orally ingested daily over 2 courses of each therapy. In the placebo group, the total scores for QOL were lower on day 8 of the second course of chemotherapy compared with the baseline scores, whereas in the LEM group the scores had not decreased. In the placebo group, the QOL functional well-being score was lower on day 8 after both the first and second courses of chemotherapy compared with the baseline score, but it had not decreased in the LEM group. Evaluation of immunological parameters indicated that an increase in the proportion of regulatory T cells to peripheral blood CD4+ cells tended to be inhibited in the LEM group compared with the placebo group. Oral LEM that was coadministered with anthracycline-based chemotherapies was useful for maintaining patients' QOL and immune function. Thus, LEM appears to be a useful oral adjuvant for patients receiving anthracycline-based chemotherapy.

Cytokines can affect the quantity and class of allergen-specific immunoglobulins through the T cell polarization that accompanies atopy. Antigen-specific IgG subclasses and IgE antibodies were compared with intracellular T cell cytokine changes to sensitizing antigens in 23 children with multiple food allergies and 20 healthy controls. Allergic children showed higher levels of total and food-specific IgE, IgG1 and IgG4 to peanut, milk and egg than non-atopic children or adults, coinciding with a TH2 cytokine response to sensitizing antigens. IgG1 and IgG4 antibodies specific to milk and egg and peanut protein were elevated relative to age-matched healthy children (p

The contribution of different T cell subsets to the overall measured cytokine response to food allergens is largely unexplored.
The patterns of cytokine production of peripheral blood-derived T cells after allergen stimulation were studied in 22 children with multiple food allergies and in 20 non-allergic children as controls, using flow cytometry.
Proportions of T cells of food-sensitized children spontaneously secreting IFN-gamma and IL-10 (without antigen stimulation) were lower than non-atopic children and adult controls (P