Dendritic Cells as a Therapeutic Strategy in Acute Myeloid Leukemia: Vaccines.

Dendritic cells (DCs) serve as professional antigen-presenting cells (APC) bridging innate and adaptive immunity, playing an essential role in triggering specific cellular and humoral responses against tumor and infectious antigens. Consequently, various DC-based antitumor therapeutic strategies have been developed, particularly vaccines, and have been intensively investigated specifically in the context of acute myeloid leukemia (AML). This hematological malignancy mainly affects the elderly population (those aged over 65), which usually presents a high rate of therapeutic failure and an unfavorable prognosis. In this review, we examine the current state of development and progress of vaccines in AML. The findings evidence the possible administration of DC-based vaccines as an adjuvant treatment in AML following initial therapy. Furthermore, the therapy demonstrates promising outcomes in preventing or delaying tumor relapse and exhibits synergistic effects when combined with other treatments during relapses or disease progression. On the other hand, the remarkable success observed with RNA vaccines for COVID-19, delivered in lipid nanoparticles, has revealed the efficacy and effectiveness of these types of vectors, prompting further exploration and their potential application in AML, as well as other neoplasms, loading them with tumor RNA.

Sulforaphane Reduces the Chronic Inflammatory Immune Response of Human Dendritic Cells.

BACKGROUND: Sulforaphane (SFN) is an isothiocyanate of vegetable origin with potent antioxidant and immunomodulatory properties. The characterization of its pleiotropic activity in human dendritic cells (DCs) is poorly summarized. The aim of this work was to study the immunomodulatory power of SFN in response to an inflammatory microenvironment on human monocyte-derived DCs (moDCs). METHODS: We studied the immunological response induced by SFN. Apoptosis and autophagy assays were performed using flow cytometry on moDCs and a cancer cell line (THP-1). These included moDC maturation, lymphocyte proliferation and cytokine production under different experimental conditions. We investigated whether these results were associated with an inflammatory microenvironment induced by lipopolysaccharides (LPSs). RESULTS: Our results demonstrated that SFN could interact with moDCs, significantly reducing the autophagy process and enhancing apoptosis similarly to cancer cell line THP-1 cells in a chronic inflammatory microenvironment. Under chronic inflammation, SFN modulated the phenotypical characteristics of moDCs, reducing the expression of all markers (CD80, CD83, CD86, HLA-DR and PD-L1). SFN significantly reduced the Th2 proliferative response, with a decrease in the IL-9 and IL-13 levels. Although we did not observe any changes in the regulatory proliferative response, we noted an increase in the IL-10 levels. CONCLUSIONS: These findings demonstrate that SFN exerts protective effects against LPS-induced inflammation via the modulation of moDCs/T cells towards a regulatory profile. SFN may be a potential candidate for the treatment of pathologies with an inflammatory profile.

Nutraceuticals as Potential Therapeutic Modulators in Immunometabolism.

Nutraceuticals act as cellular and functional modulators, contributing to the homeostasis of physiological processes. In an inflammatory microenvironment, these functional foods can interact with the immune system by modulating or balancing the exacerbated proinflammatory response. In this process, immune cells, such as antigen-presenting cells (APCs), identify danger signals and, after interacting with T lymphocytes, induce a specific effector response. Moreover, this conditions their change of state with phenotypical and functional modifications from the resting state to the activated and effector state, supposing an increase in their energy requirements that affect their intracellular metabolism, with each immune cell showing a unique metabolic signature. Thus, nutraceuticals, such as polyphenols, vitamins, fatty acids, and sulforaphane, represent an active option to use therapeutically for health or the prevention of different pathologies, including obesity, metabolic syndrome, and diabetes. To regulate the inflammation associated with these pathologies, intervention in metabolic pathways through the modulation of metabolic energy with nutraceuticals is an attractive strategy that allows inducing important changes in cellular properties. Thus, we provide an overview of the link between metabolism, immune function, and nutraceuticals in chronic inflammatory processes associated with obesity and diabetes, paying particular attention to nutritional effects on APC and T cell immunometabolism, as well as the mechanisms required in the change in energetic pathways involved after their activation.