New immunotherapy approaches as the most effective treatment for uveal melanoma.

Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Conventional methods of UM treatment are based on chemotherapy and radiotherapy, which have been able to control tumor growth in a limited way. But due to the inadequacy and many side effects of these treatments, many UM patients die during treatment, and approximately 50% of patients develop metastasis. Meanwhile, the 2-year survival rate of these patients from the time of metastasis is 8%. Since immunotherapy has the potential to be the most specific and efficient method in the treatment of tumors, it is considered an attractive and promising research field in the treatment of UM. This review highlights recent advances in UM immunotherapy and provides new immunological approaches on how to overcome the challenges of UM immunotherapy.

Recent approaches in regenerative medicine in the fight against neurodegenerative disease.

Neurodegenerative diseases arise due to slow and gradual loss of structure and/or function of neurons and glial cells and cause different degrees of loss of cognition abilities and sensation. The little success in developing effective treatments imposes a high and regressive economic impact on society, patients and their families. In recent years, regenerative medicine has provided a great opportunity to research new innovative strategies with strong potential to treatleva these diseases. These effects are due to the ability of suitable cells and biomaterials to regenerate damaged nerves with differentiated cells, creating an appropriate environment for recovering or preserving existing healthy neurons and glial cells from destruction and damage. Ultimately, a better understanding and thus a further investigation of stem cell technology, tissue engineering, gene therapy, and exosomes allows progress towards practical and effective treatments for neurodegenerative diseases. Therefore, in this review, advances currently being developed in regenerative medicine using animal models and human clinical trials in neurological disorders are summarized.

PEGylated single-walled carbon nanotubes as co-adjuvants enhance expression of maturation markers in monocyte-derived dendritic cells.

Aim: This study investigated the application of phospholipid-PEGylated single-walled carbon nanotubes (PL-PEG-SWCNTs) as a safe co-adjuvant for the commercial recombinant hepatitis B virus vaccine to enhance induction of monocyte-derived dendritic cells (MDDCs) differentiation and activation in vitro as an immune response initiator cell to prompt a long-term immune response after a single dose injection. Methods: Immature MDDCs were exposed to PL-PEG-SWCNTs alone and in combination with hepatitis B vaccine. Results & conclusion: Study results confirm the enhanced expression of maturation markers in human immature MDDCs after PL-PEG-SWCNT exposure. The results suggest that PL-PEG-SWCNT is an efficient co-adjuvant for the commercial recombinant hepatitis B virus vaccine to enhance dendritic cell response stimulation in vitro.

Frequency of dendritic cell subsets and ILT3, ILT4 gene expression in two different immunosuppressive protocols in kidney transplant recipients. A cohort report.

Dendritic cells (DCs) have a major role in the initiation of an immune response and Immunoglobulin-like transcript 3&4 (ILT3&ILT4) are inhibitory receptors that induce tolerance in DCs. Recent studies show that immunosuppressive agents affect frequency of DCs. Herein, we compared the effect of mycophenolate mofetil (MMF) and sirolimus (SRL) in tacrolimus (TAC)-based immunosuppression on DC subsets frequency and ILT3/ILT4 gene expression in kidney transplant recipients. We enrolled 24 adult transplant recipients who received MMF/TAC (n = 14) or SRL/TAC (n = 10). Peripheral blood samples were obtained from recipients, 24-48 h before transplantation and 4 months after transplantation. The frequency of DC subsets was analyzed by flow cytometry and gene expression of ILT3/ILT4 were estimated by real-time PCR. Our results showed that MMF vs. SRL treated recipient showed an increase in pDC % with increased in the expression of ILT3/ILT4 which is in favor of better allograft survival; However, for confirming the results of this preliminary study, a cohort study with larger sample size is necessary.

Sirolimus vs mycophenolate moftile in Tacrolimus based therapy following induction with Antithymocyte globulin promotes regulatory T cell expansion and inhibits RORγt and T-bet expression in kidney transplantation.

BACKGROUND: Accumulating evidence suggests that regulatory T cells (Tregs) have a crucial role in immune tolerance and long-term graft survival. However, the influence of immunosuppressive drugs on the level of Tregs has not been fully understood. Therefore we prospectively compare the effect of two different calcineurin inhibitor (CNI)-based immunosuppression protocols on Tregs frequencies and expression of regulatory and effector T cell-related genes in renal transplant recipients. METHODS: The study included 24 renal transplant recipients who received induction therapy (Antithymocyte globulin) and were on triple immunosuppressive therapy so that one group was on Tacrolimus (Tac), mycophenolate moftile (MMF) and prednisolone (P) whereas another group was on Tac, Sirolimus (SRL) and P. The frequency of circulating Treg cells was analyzed by flow cytometry before and 4 months after transplantation. Also, the mRNA expression of FOXP3, T-bet, GATA3 and RORγt was examined by quantitative RT-PCR before and 4 months after transplantation. RESULTS: Compared to baseline, the frequency of CD4+ CD25+ FOXP3+ Treg cells was significantly increased in the all patients following transplantation. Patients who received Tac/MMF had significantly higher CD4+ CD25+ FOXP3+ Treg cells compared to patients who received Tac/SRL. There was no a significant difference in the frequency of CD3+CD8+ CD28- Tregs between two different calcineurin inhibitor (CNI)-based immunosuppression protocols. FOXP3 mRNA levels in the patients who received Tac/MMF were increased 4 months after transplantation and the expression was significantly higher than patients who received Tac/SRL. On the other hand, T-bet and RORγt expression levels were significantly lower in the Tac/SRL group in comparison to Tac/MMF group. We did not observe any significant difference in GATA3 mRNA level between the two groups. CONCLUSIONS: Our results suggest that although Tac/MMF-containing immunosuppressive regimen could significantly increase the frequency of CD4+ CD25+ FOXP3+ Tregs, unlike to Tac/SRL-containing regimen, it could not significantly decrease the expression levels of RORγt and T-bet.

Th1, Th2, Th17 cell subsets in two different immunosuppressive protocols in renal allograft recipients (Sirolimus vs mycophenolate mofetil): A cohort study.

Long-term use of calcineurin inhibitors (CNI) is associated with nephrotoxicity, which is an important cause of renal dysfunction. Therefore, CNI-minimization strategies which decrease the CNI nephrotoxicity under the protection of additional immunosuppressant drugs have been developed. The aim of current cohort study was to compare the effect of two immunosuppressive protocols [tacrolimus (TAC) in combination with mycophenolate mofetil (MMF) and prednisolone (PRED) versus TAC in combination with sirolimus (SRL) and prednisolone] on the frequency of T helper cell subsets (Th1, Th2 and Th17 cells) and their associated cytokine (IFN-γ, IL-4 and IL-17A) levels in renal allograft recipients. In this study, renal transplant recipients who received induction therapy (Antithymocyte globulin) and were also on triple immunosuppressive therapy were included and divided in to two groups: Group A was comprised 14 patients who received TAC, MMF and PERD whereas group B was composed of 10 patients who received TAC, SRL and PERD. The frequency of Th1, Th2 and Th17 cells in the peripheral blood mononuclear cells (PBMCs) of the patients was analyzed by flow cytometry before and 4 months after transplantation. In addition, IFN-γ, IL-4 and IL-17A concentrations in PBMC culture supernatants of patients before and 4 months after transplantation were quantified by ELISA. The results of our study showed that TAC, MMF and PRED protocol did not diminish the frequency of Th17 cells at 4 months post-transplantation (5% ±â€¯2.5) compared with pre-transplantation (2.3% ±â€¯1; P < 0.05). However, Th17 (3.6% ±â€¯1.5 pre-transplantation vs 2.2% ±â€¯0.9 at 4 months post-transplantation; P < 0.05), Th2 (1.4% ±â€¯0.3 pre-transplantation vs 0.8% ±â€¯0.4 at 4 months post-transplantation; P < 0.05) cell subsets and IL-4 concentration (71.5 pg/ml ±â€¯12 pre-transplantation vs 62.5 pg/ml ±4.4 at 4 months post-transplantation; P < 0.05) were significantly decreased after transplantation in patients who had received SRL, TAC and PRED. In conclusion, the data of the current study suggest that using reduced dose of TAC in SRL, TAC and PRED protocol is in favor of allograft survival; however a cohort study with larger sample size is needed for confirming our results.