Dendritic cell vaccination strategy for the treatment of acute myeloid leukemia: a systematic review.

BACKGROUND AIMS: Acute myeloid leukemia (AML) is classified as a hematologic malignancy characterized by the proliferation of immature blood cells within the bone marrow (BM), resulting in an aberrant and unregulated cellular growth. The primary therapeutic modalities for AML include chemotherapy and hematopoietic stem cell transplantation. However, it is important to note that these treatments are accompanied by important adverse effects and mortality rates. Therefore, the need for more effective treatment options seems necessary, and dendritic cell (DC) vaccine therapy can be one of these options. In this study, we aim to investigate the effectiveness of DC vaccination therapy for the management of AML. METHODS: PubMed, Scopus, ProQuest, Web of Science, and Google Scholar databases were searched for this systematic review. The articles were evaluated based on the inclusion criteria of this study and initially compared in terms of titles or abstracts. Finally, the articles related to the topic of this review were obtained in full text. The complete remission and partial remission, survival, correlative immune assays, and health-related metrics were used to evaluate this cellular immunotherapy effectiveness. The quality of the studies was assessed independently using the Cochrane risk-of-bias tools. The compiled data were input into a standard Excel spreadsheet. Each domain was evaluated as having either a "low risk," "high risk," or "unclear risk" of bias. RESULTS: Among the 3986 studies that were determined, a total of 11 correlated trials were selected for inclusion in this systematic review. DC vaccine therapy was effective in inducing complete and partial remission, and stabilization of the disease. Additionally, it was discovered that the treatment strengthened the immune system as seen by increased levels of CD4+ and CD8+ T cells, Th1 cytokines, WT1-specific T cells, and activated NK cells. CONCLUSION: We conducted a systematic review that supports the use of DC vaccine therapy as an effective treatment for AML. The therapy demonstrated potentials in achieving remission, enhancing the immune system function, and increasing overall survival. However, more studies are required to improve the methods of preparing and delivering the DC vaccine, and to confirm its long-term safety and effectiveness.

Dopamine receptor agonist cabergoline promotes immunogenic phenotype in human monocyte-derived dendritic cells.

Dendritic cells (DCs) are known as antigen-presenting cells that are capable of regulating immune responses. DCs and T cells can interact mutually to induce antigen-specific T-cell responses. Cabergoline, which is a dopamine (DA) receptor agonist, seems to implement anti-inflammatory properties in the immune system, and therefore in the present study the impact of a DA receptor agonist cabergoline on the monocyte-derived DCs (moDCs) was assessed. Immature moDCs were treated with lipopolysaccharide to produce mature DCs (mDCs). The expression of DCs' related surface markers namely: CD11c, HLA-DR, and CD86 was measured by utilizing of flow cytometry. Real-time PCR was the technique of choice to determine the levels at which diverse inflammatory and anti-inflammatory factors in cabergoline-treated and control mDC groups were expressed. DCs treated with cabergoline displayed a significant decrease in CD86 and HLA-DR expression, markers linked to maturation and antigen presentation, respectively. In addition, the cabergoline-mDC group showed a considerable decline in terms of the levels at which IL-10, TGF-ß, and IDO genes were expressed, and an increase in the expression of TNF-α and IL-12 in comparison to the mDC control group. Our findings revealed that cabergoline as an immunomodulatory agent can relatively shift DCs into an immunogenic state, and there is a requirement for further investigations to evaluate the effects of cabergoline-treated DCs on the T cell responses in vitro, and also in various diseases including cancer in animal models.

Everolimus treatment enhances inhibitory immune checkpoint molecules' expression in monocyte-derived dendritic cells.

BACKGROUND: Antigen-specific T-cell immunity is provided by dendritic cells (DCs), which are specialized antigen-presenting cells. Furthermore, they establish a link between innate and adaptive immune responses. Currently, DC modification is a new approach for the therapy of several disorders. During solid organ transplantation, Everolimus, which is a mammalian target of rapamycin (mTOR) inhibitor, was initially utilized to suppress the immune system's functionality. Due to the intervention of Everolimus in various signaling pathways in cells and its modulatory properties on the immune system, this study aims to investigate the effect of treatment with Everolimus on the maturation and expression of immune checkpoint genes in monocyte-derived DCs. METHODS: To isolate monocytes from PBMCs, the CD14 marker was used via the MACS method. Monocytes were cultured and induced to differentiate into monocyte-derived DCs by utilizing GM-CSF and IL-4 cytokines. On the fifth day, immature DCs were treated with Everolimus and incubated for 24 h. On the sixth day, the flow cytometry technique was used to investigate the effect of Everolimus on the phenotypic characteristics of DCs. In the end, the expression of immune checkpoint genes in both the Everolimus-treated and untreated DCs groups was assessed using the real-time PCR method. RESULTS: The findings of this research demonstrated that the administration of Everolimus to DCs led to a notable rise in human leukocyte antigen (HLA)-DR expression and a decrease in CD11c expression. Furthermore, there was a significant increase in the expression of immune checkpoint molecules, namely CTLA-4, VISTA, PD-L1, and BTLA, in DCs treated with Everolimus. CONCLUSION: The findings of this study show that Everolimus can target DCs and affect their phenotype and function in order to shift them toward a partially tolerogenic state. However, additional research is required to gain a comprehensive understanding of the precise impact of Everolimus on the activation status of DCs.