OBJECTIVE Type 1 diabetes is a condition in which pancreatic islets are destroyed by self-reactive T cells. The process is facilitated by deficits in the number and suppressive activity of regulatory T cells (Tregs). Here, we show for the first time that the infusion of autologous Tregs prolongs remission in recently diagnosed type 1 diabetes in children. RESEARCH DESIGN AND METHODS We have administered Tregs in 10 type 1 diabetic children (aged 8–16 years) within 2 months since diagnosis. In total, 4 patients received 10 × 10⁶ Tregs/kg body wt, and the remaining 6 patients received 20 × 10⁶ Tregs/kg body wt. The preparation consisted of sorted autologous CD3⁺CD4⁺CD25^highCD127⁻ Tregs expanded under good manufacturing practice conditions. RESULTS No toxicity of the therapy was noted. A significant increase in the percentage of Tregs in the peripheral blood has been observed since the day of infusion. These patients were followed along with matched type 1 diabetic patients not treated with Tregs. Half a year after type 1 diabetes onset (4–5 months after Tregs infusion), 8 patients treated with Tregs still required <0.5 UI/kg body wt of insulin daily, with 2 patients out of insulin completely, whereas the remission was over in the nontreated group. In addition, plasma C-peptide levels were significantly higher in the treated group as compared with those not treated. CONCLUSIONS This study shows that the administration of Tregs is safe and tolerable in children with recent-onset type 1 diabetes.

In recent years, a lot of scientific interest has focused on cancer immunotherapy. Although chronic inflammation has been described as one of the hallmarks of cancer, acute inflammation can actually trigger the immune system to fight diseases, including cancer. Toll-like receptor (TLR) ligands have long been used as adjuvants for traditional vaccines and it seems they may also play a role enhancing efficiency of tumor immunotherapy. The aim of this perspective is to discuss the effects of TLR stimulation in cancer, expression of various TLRs in different types of tumors, and finally the role of TLRs in anti-cancer immunity and tumor rejection.

Gut microbiota and its association with cancer development/treatment has been intensively studied during the past several years. Currently, there is a growing interest toward next-generation probiotics (NGPs) as therapeutic agents that alter gut microbiota and impact on cancer development. In the present review we focus on three emerging NGPs, namely Faecalibacterium prausnitzii, Akkermansia muciniphila, and Bacteroides fragilis as their presence in the digestive tract can have an impact on cancer incidence. These NGPs enhance gastrointestinal immunity, maintain intestinal barrier integrity, produce beneficial metabolites, act against pathogens, improve immunotherapy efficacy, and reduce complications associated with chemotherapy and radiotherapy. Notably, the use of NGPs in cancer patients does not have a long history and, although their safety remains relatively undefined, recently published data has shown that they are non-toxigenic. Notwithstanding, A. muciniphila may promote colitis whereas enterotoxigenic B. fragilis stimulates chronic inflammation and participates in colorectal carcinogenesis. Nevertheless, the majority of B. fragilis strains provide a beneficial effect to the host, are non-toxigenic and considered as the best current NGP candidate. Overall, emerging studies indicate a beneficial role of these NGPs in the prevention of carcinogenesis and open new promising therapeutic options for cancer patients.

Improper activation of the immune system contributes to a variety of clinical conditions, including autoimmune and allergic diseases as well as solid organ and bone marrow transplantation. One approach to counteract this activation is through adoptive therapy with regulatory T cells (T_regs). Efforts to manufacture these cells have led to good maunfacturing practice–compliant protocols, and T_reg products are entering early clinical trials. Here, we report the stance of the European Union Cooperation in Science and Technology Action BM1305, “Action to Focus and Accelerate Cell-based Tolerance-inducing Therapies—A FACTT,” which identifies hurdles hindering T_reg clinical applications in Europe and provides possible solutions.