Myeloid-derived suppressor cells (MDSCs) are major immunosuppressive cells that lead to T cell defects in cancer. IL-18 is important in inflammatory and immune responses. IL-18 has been reported to have a dual effect on tumor progression, as it not only stimulates host immune responses, but also exerts procancer effects by inducing immune escape and angiogenesis. In the present study, we investigated the effect of IL-18 on MDSCs and found that IL-18 treatment significantly increased the percentage and the absolute number of monocytic MDSCs (M-MDSCs) via differentiation of CD11b− bone marrow progenitor cells. IL-18–induced MDSCs showed enhanced suppression of T cell proliferation and IFN-γ production along with a dramatic increase of M-MDSC suppressive function, including NO production and arginase 1 expression. Although IL-18 decreased the number of granulocytic MDSCs (G-MDSCs) in a concentration-dependent manner, we found that the absolute number of G-MDSCs and their reactive oxygen species production remained unchanged. Additionally, we demonstrated that IL-18–induced M-MDSCs have a more potent suppressive effect on T cell responses with lower IFN-γ production than do G-MDSCs, suggesting that the increased suppressive effect observed in our study resulted from M-MDSCs. Furthermore, in vivo administration of IL-18 significantly increased the accumulation of M-MDSCs in the tumor microenvironment. Taken together, our findings indicate that IL-18 specifically enhances the differentiation and function of M-MDSCs, leading to immunosuppression.

Mucosal surfaces are the first site of infection for most infectious diseases and oral vaccination can provide protection as the first line of defense. Unlike systemic administration, oral immunization can stimulate cellular and humoral immune responses at both systemic and mucosal levels to induce broad-spectrum and long-lasting immunity. Therefore, to design a successful vaccine, it is essential to stimulate the mucosal as well as systemic immune responses. Successful oral vaccines need to overcome the harsh gastrointestinal environment such as the extremely low pH, proteolytic enzymes, bile salts as well as low permeability and the low immunogenicity of vaccines. In recent years, several delivery systems and adjuvants have been developed for improving oral vaccine delivery and immunogenicity. Formulation of vaccines with nanoparticles and microparticles have been shown to improve antigen stability, availability and adjuvanticity as well as immunostimulatory capacity, target delivery and specific release. This review discusses how nanoparticles (NPs) and microparticles (MPs) as oral carriers with adjuvant characteristics can be beneficial in oral vaccine development.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic involving so far more than 15 million infections and 630,211 deaths. Effective vaccines are urgently needed to prevent SARS-CoV-2 infections. No vaccines have yet been approved for licensure by regulatory agencies. Even though host immune responses to SARS-CoV-2 infections are beginning to be unravelled, effective clearance of virus will depend on both humoral and cellular immunity. Additionally, the presence of Spike (S)-glycoprotein reactive CD4+ T-cells in the majority of convalescent patients is consistent with its significant role in stimulating B and CD8+ T-cells. The search for immunodominant epitopes relies on experimental evaluation of peptides representing the epitopes from overlapping peptide libraries which can be costly and labor-intensive. Recent advancements in B- and T-cell epitope predictions by bioinformatic analysis have led to epitope identifications. Assessing which peptide epitope can induce potent neutralizing antibodies and robust T-cell responses is a prerequisite for the selection of effective epitopes to be incorporated in peptide-based vaccines. This review discusses the roles of B- and T-cells in SARS-CoV-2 infections and experimental validations for the selection of B-, CD4+ and CD8+ T-cell epitopes which could lead to the construction of a multi-epitope peptide vaccine. Peptide-based vaccines are known for their low immunogenicity which could be overcome by incorporating immunostimulatory adjuvants and nanoparticles such as Poly Lactic-co-Glycolic Acid (PLGA) or chitosan.

There has been a great interest in myeloid-derived suppressor cells (MDSCs) due to their biological functions in tumor-mediated immune escape by suppressing antitumor immune responses. These cells arise from altered myelopoiesis in response to the tumor-derived factors. The most recognized function of MDSCs is suppressing anti-tumor immune responses by impairing T cell functions, and these cells are the most important players in cancer dissemination and metastasis. Therefore, understanding the factors and the mechanism of MDSC differentiation, expansion, and recruitment into the tumor microenvironment can lead to its control. However, most of the studies only defined MDSCs with no further characterization of granulocytic and monocytic subsets. In this review, we discuss the mechanisms by which specific MDSC subsets contribute to cancers. A better understanding of MDSC subset development and the specific molecular mechanism is needed to identify treatment targets. The understanding of the specific molecular mechanisms responsible for MDSC accumulation would enable more precise therapeutic targeting of these cells.

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