Dexamethasone turns tumor antigen-presenting cells into tolerogenic dendritic cells with T cell inhibitory functions

BackgroundDendritic cells (DCs) are usually immunogenic, but they are also capable of inducing tolerance under anti-inflammatory conditions. Immunotherapy based on autologous DCs loaded with an allogeneic melanoma cell lysate (TRIMEL/DCs) induces immunological responses and increases melanoma patient survival. Glucocorticoids can suppress DC maturation and function, leading to a DC-mediated inhibition of T cell responses.MethodsThe effect of dexamethasone, a glucocorticoid extensively used in cancer therapies, on TRIMEL/DCs phenotype and immunogenicity was examined.ResultsDexamethasone induced a semi-mature phenotype on TRIMEL/DC with low maturation surface marker expressions, decreased pro-inflammatory cytokine induction (IL-1β and IL-12) and increased release of regulatory cytokines (IL-10 and TGF-β). Dexamethasone-treated TRIMEL/DCs inhibited allogeneic CD4⁺ T cell proliferation and cytokine release (IFNγ, TNF-α and IL-17). Co-culturing melanoma-specific memory tumor-infiltrating lymphocytes with dexamethasone-treated TRIMEL/DC inhibited proliferation and effector T cell activities, including cytokine secretion and anti-melanoma cytotoxicity.ConclusionsThese findings suggest that dexamethasone repressed melanoma cell lysate-mediated DC maturation, generating a potent tolerogenic-like DC phenotype that inhibited melanoma-specific effector T cell activities. These results suggest that dexamethasone-induced immunosuppression may interfere with the clinical efficacy of DC-based melanoma vaccines, and must be taken into account for optimal design of cellular therapy against cancer.     

Role of pentamer complex-specific and IgG subclass 3 antibodies in HCMV hyperimmunoglobulin and standard intravenous IgG preparations

Medical Microbiology and Immunology - HCMV hyperimmunoglobulin-preparations (HIG) contain high concentrations of HCMV-specific IgG. The reduced maternofetal-HCMV-transmission rate of IgG may be due...     

Warranting the decision-maker,not the decision: How healthcare practitioners evaluate the legitimacy of patients’ unprompted requests for risk-reducing mastectomy

ObjectiveShared decision-making exists to reconcile healthcare practitioners’ responsibilities to respect patients’ autonomy whilst ensuring well-made decisions. Patients sometimes make unprompted requests for procedures that carry medical and other risks, such as risk-reducing mastectomy (RRM). Faced with pre-formed decisions into which they have had little input, it is unclear how practitioners can reconcile respecting autonomy with ensuring well-made decisions.MethodsQualitative study of linked patient-practitioner interviews in a breast unit in North-West England. We examined how 10 practitioners addressed 19 patients’ unprompted requests for RRM.ResultsPractitioners empathised with patients’ distress about cancer risk, regarded RRM as legitimate to help, but were wary of choices made ‘emotionally’. Practitioners did not seek to establish whether choices were well-made but, instead, ‘warranted’ patients by satisfying themselves that patients were ‘sensible’ and ‘informed’ decision-makers, and thus their decisions could be trusted. Practitioners provided information, and tested patients’ resolve by delaying decisions and presenting ‘what if’ scenarios depicting failure or harm from RRM.ConclusionPatients who present emotionally and with resolution can receive RRM without evidence of a well-made decision.Practice Implications: Argumentation theory proposes an ethically robust and clinically practicable approach, whereby practitioners elicit, examine and, where appropriate, challenge arguments underpinning patients’ decisions.     

Description of two new species of allocreadiid trematodes (Digenea: Allocreadiidae) in middle American freshwater fishes using an integrative taxonomy approach

Parasitology Research - Integrative taxonomy uses several sources of information to establish more robust species delimitation criteria. In this study, we followed that approach to describe two new...     

Taxonomic status of Rhabdochona ictaluri (Nematoda: Rhabdochonidae) based on molecular and morphological evidence

The genus Rhabdochona includes more than 100 species infecting freshwater fishes in all zoogeographical regions of the world. In Mexico, 12 nominal species of Rhabdochona have been recorded. Of these, Rhabdochona ictaluri was originally described as a parasite of endemic catfishes of the family Ictaluridae; however, the species was later considered on morphological grounds as a junior synonym of Rhabdochona kidderi. In this study, newly sampled specimens of R. ictaluri were obtained from the type host and type locality and were used to perform a detailed morphological analysis and molecular phylogenetic inferences through one mitochondrial and two nuclear genes; data were used in an integrative taxonomy context to test the taxonomic status of R. ictaluri. This approach proved to be very useful to confirm the validity of this species, and robust species limits were established between these two putative species considering morphology, molecular data, host association, and biogeography.

     

ER stress abrogates the immunosuppressive effect of IL-10 on human macrophages through inhibition of STAT3 activation

Inflammation Research - To determine whether ER stress affects the inhibitory pathways of the human immune system, particularly the immunosuppressive effect of IL-10 on macrophages. In vitro...     

Fructose 1,6-bisphosphate inhibits osteoclastogenesis by attenuating RANKL-induced NF-κB/NFATc-1

Inflammation Research - Although some glycolytic intermediates have been shown to modulate several cell type formation and activation, the functional role of fructose 1,6-bisphosphate (FBP) on...     

The effects of parenteral nutrition on food intake and gastric motility

Frequently, patients receiving parenteral nutrition (PN) report hunger during the parenteral infusion, yet experience early satiety once PN is tapered off. Post-PN satiety can interfere with the ability to consume enough nutrients to maintain body weight and nutritional status. Factors such as caloric quantity of infusate, gastric motility changes, and disease pathology have been related to appetite changes. To investigate the effects of PN on food intake and gastric motility without the complicated interactions associated with disease pathology, four normal, healthy rhesus monkeys (Macaca mulatta) were studied. The monkeys were administered PN in amounts ranging from 25% to 100% of their normal daily caloric intake. Food and water were continuously available. PN consistently suppressed voluntary food intake in direct relationship to the amount of nutrient infused. The frequency of large-amplitude hunger-type gastric contractions decreased from control conditions. Upon cessation of PN, appetite remained suppressed for one to two weeks, indicating a self-limiting physiological basis to post-PN satiety. Thus, reduced appetite following PN termination might occur in the clinical setting and the patients' feelings of satiety may not be completely attributed to lack of cooperation or disease pathology.