CIMT 2022: Report on the 19th Annual Meeting of the Association for Cancer Immunotherapy.

The 19th Annual Meeting of the Association for Cancer Immunotherapy (CIMT), Europe's cancer immunotherapy meeting, was the first in-person event organized by CIMT since the beginning of the COVID-19 pandemic. As a hybrid event from May 10-12, the meeting attracted 920 academic and clinical professionals from over 40 countries, who met to discuss the latest advances in cancer immunology and immunotherapy research. This report summarizes the highlights of CIMT2022.

Multi-omics profiling of collagen-induced arthritis mouse model reveals early metabolic dysregulation via SIRT1 axis.

Rheumatoid arthritis (RA) is characterized by joint infiltration of immune cells and synovial inflammation which leads to progressive disability. Current treatments improve the disease outcome, but the unmet medical need is still high. New discoveries over the last decade have revealed the major impact of cellular metabolism on immune cell functions. So far, a comprehensive understanding of metabolic changes during disease development, especially in the diseased microenvironment, is still limited. Therefore, we studied the longitudinal metabolic changes during the development of murine arthritis by integrating metabolomics and transcriptomics data. We identified an early change in macrophage pathways which was accompanied by oxidative stress, a drop in NAD+ level and induction of glucose transporters. We discovered inhibition of SIRT1, a NAD-dependent histone deacetylase and confirmed its dysregulation in human macrophages and synovial tissues of RA patients. Mining this database should enable the discovery of novel metabolic targets and therapy opportunities in RA.

No Cytotoxic and Inflammatory Effects of Empagliflozin and Dapagliflozin on Primary Renal Proximal Tubular Epithelial Cells under Diabetic Conditions In Vitro.

Gliflozins are inhibitors of the renal proximal tubular sodium-glucose co-transporter-2 (SGLT-2), that inhibit reabsorption of urinary glucose and they are able to reduce hyperglycemia in patients with type 2 diabetes. A renoprotective function of gliflozins has been proven in diabetic nephropathy, but harmful side effects on the kidney have also been described. In the current project, primary highly purified human renal proximal tubular epithelial cells (PTCs) have been shown to express functional SGLT-2, and were used as an in vitro model to study possible cellular damage induced by two therapeutically used gliflozins: empagliflozin and dapagliflozin. Cell viability, proliferation, and cytotoxicity assays revealed that neither empagliflozin nor dapagliflozin induce effects in PTCs cultured in a hyperglycemic environment, or in co-medication with ramipril or hydro-chloro-thiazide. Oxidative stress was significantly lowered by dapagliflozin but not by empagliflozin. No effect of either inhibitor could be detected on mRNA and protein expression of the pro-inflammatory cytokine interleukin-6 and the renal injury markers KIM-1 and NGAL. In conclusion, empa- and dapagliflozin in therapeutic concentrations were shown to induce no direct cell injury in cultured primary renal PTCs in hyperglycemic conditions.

Meta-analysis of psychological treatments for posttraumatic stress disorder in adult survivors of childhood abuse.

Posttraumatic stress disorder (PTSD) is highly prevalent in adult survivors of childhood sexual and/or physical abuse. However, intervention studies focusing on this group of patients are underrepresented in earlier meta-analyses on the efficacy of PTSD treatments. The current meta-analysis exclusively focused on studies evaluating the efficacy of psychological interventions for PTSD in adult survivors of childhood abuse. Sixteen randomized controlled trials meeting inclusion criteria could be identified that were subdivided into trauma-focused cognitive behavior therapy (CBT), non-trauma-focused CBT, eye movement desensitization and reprocessing, and other treatments (interpersonal, emotion-focused). Results showed that psychological interventions are efficacious for PTSD in adult survivors of childhood abuse, with an aggregated uncontrolled effect size of g=1.24 (pre- vs. post-treatment), and aggregated controlled effect sizes of g=0.72 (post-treatment, comparison to waitlist control conditions) and g=0.50 (post-treatment, comparison with TAU/placebo control conditions), respectively. Effect sizes remained stable at follow-up. As the heterogeneity between studies was large, we examined the influence of two a priori specified moderator variables on treatment efficacy. Results showed that trauma-focused treatments were more efficacious than non-trauma-focused interventions, and that treatments including individual sessions yielded larger effect sizes than pure group treatments. As a whole, the findings are in line with earlier meta-analyses showing that the best effects can be achieved with individual trauma-focused treatments.