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Simple Summary: The Major histocompatibility complex (Mhc) plays an essential role in antigen presentation as part of the adaptive immune system. To investigate the role of MhcII in adaptive immunity, this study cloned the mhcIIα and mhcIIβ of flounder (Paralichthys olivaceus) and examined their distribution and expression patterns, which varied by antigen stimulation or pathogens infection. The analyses showed that they were significantly expressed in gills, spleen, and peripheral blood leukocytes (PBLs), and MhcII molecules were co-localized with CD83 and IgM on leukocytes, respectively. The expression of both mhcIIα and mhcIIβ were significantly upregulated in flounder after infection. The percentages of MhcII+ cells, MhcII+/CD83+, and MhcII+/IgM+ cells increased significantly after PHA and ConA stimulation, respectively; they varied significantly in PBLs after polyI:C stimulation and no obvious variations were found after LPS treatment. These results suggested that MhcII, mainly expressed in B cells and dendritic cells, responded significantly to exogenous antigens and T cell-dependent antigens. In conclusion, MhcII was associated with cellular immunity in teleosts. The Major histocompatibility complex (Mhc) is an important molecule for antigen presenting and binds to T cell receptors, activating T lymphocytes and triggering specific immune responses. To investigate the role of MhcII in adaptive immunity, in this study, mhcIIα and mhcIIβ of flounder (Paralichthys olivaceus) were cloned, polyclonal antibodies (Abs) against their extracellular regions were produced, respectively, and their distribution on cells and tissues and expression patterns, which varied by antigen stimulation or pathogen infection, were investigated. The results showed that the open reading frame (ORF) of mhcIIα is 708 bp, including 235 amino acids (aa); and the ORF of mhcIIβ is 741 bp, encoding 246aa. The mhcIIα and mhcIIβ were significantly expressed in gills, spleen, and peripheral blood leukocytes (PBLs). Their antibodies could specifically recognize eukaryotic expressed MhcIIα and MhcIIβ. MhcIIα+ and MhcIIβ+ cells were 30.2 ± 2.9% of the percentage in peripheral blood leukocytes. MhcII molecules were co-localized with CD83 and IgM on leukocytes, respectively, but not on CD4+ or CD8+ T lymphocyte subpopulations. The expression of both mhcIIα and mhcIIβ were significantly upregulated in flounder after bacteria and virus challenges. The percentages of MhcII+ cells, MhcII+/CD83+, and MhcII+/IgM+ double-positive cells increased significantly after PHA and ConA stimulation, respectively; they varied significantly in PBLs after polyI:C stimulation, and no variations were found after LPS treatment. In the meantime, variations in MhcII+ cells were consistent with that of CD4+ T lymphocytes. These results suggest that MhcII, mainly expressed in B cells and dendritic cells, play an essential role in antigen presentation, and respond significantly to exogenous antigens and T cell-dependent antigens. These results may provide an important reference for the study of cellular immunity in teleosts. [ABSTRACT FROM AUTHOR]

Simple Summary: The tumor immune escape mechanisms are key factors in cancer progression and metastasis. They are an undeniable hurdle for successful cancer treatment in patients. It has been widely recognized that cancer cells can escape immune surveillance and antitumor immunity. Despite host immunity, tumor cells can escape antitumor immune cell responses by several different mechanisms, such as the loss of the antigen presentation capacity by some immune cells, which promotes tumor progression and resistance to immunotherapy. A few monotherapies or combinational therapies have been approved for use in cancer treatment, but the majority of patients are not responsive to currently used immunotherapies, thus presenting a need to discover new targets to achieve efficacious immune responses to benefit cancer patients. This review focuses on some of the most important classical immune checkpoint targets and also sheds light on some of the recently discovered, promising immunotherapeutic targets and strategies. Immune checkpoint blockade (ICB) has emerged as a novel therapeutic tool for cancer therapy in the last decade. Unfortunately, a small number of patients benefit from approved immune checkpoint inhibitors (ICIs). Therefore, multiple studies are being conducted to find new ICIs and combination strategies to improve the current ICIs. In this review, we discuss some approved immune checkpoints, such as PD-L1, PD-1, and CTLA-4, and also highlight newer emerging ICIs. For instance, HLA-E, overexpressed by tumor cells, represents an immune-suppressive feature by binding CD94/NKG2A, on NK and T cells. NKG2A blockade recruits CD8+ T cells and activates NK cells to decrease the tumor burden. NKG2D acts as an NK cell activating receptor that can also be a potential ICI. The adenosine A2A and A2B receptors, CD47-SIRPα, TIM-3, LAG-3, TIGIT, and VISTA are targets that also contribute to cancer immunoresistance and have been considered for clinical trials. Their antitumor immunosuppressive functions can be used to develop blocking antibodies. PARPs, mARTs, and B7-H3 are also other potential targets for immunosuppression. Additionally, miRNA, mRNA, and CRISPR-Cas9-mediated immunotherapeutic approaches are being investigated with great interest. Pre-clinical and clinical studies project these targets as potential immunotherapeutic candidates in different cancer types for their robust antitumor modulation. [ABSTRACT FROM AUTHOR]

As poikilothermic vertebrates, fish can experience changes in water temperature, and hence body temperature, as a result of seasonal changes, migration, or efflux of large quantities of effluent into a body of water. Temperature shifts outside of the optimal temperature range for an individual fish species can have negative impacts on the physiology of the animal, including the immune system. As a result, acute or chronic exposure to suboptimal temperatures can impair an organisms'ability to defend against pathogens and thus compromise the overall health of the animal. This review focuses on the advances made towards understanding the impacts of suboptimal temperature on the soluble and cellular mediators of the innate and adaptive immune systems of fishes. Although cold stress can result in varying effects in different fish species, acute and chronic suboptimal temperature exposure generally yield suppressive effects, particularly on adaptive immunity. Knowledge of the effects of environmental temperature on fish species is critical for both the optimal management of wild species and the best management practices for aquaculture species. [ABSTRACT FROM AUTHOR]

Simple Summary: Extracellular vesicles (EVs) allow cell-to-cell communication and can induce a strong immune response, by presenting antigens. EVs can be engineered to display viral antigens and so induce high and specific CD8(+) T cell and B cell reactions, highlighting these antigen-presenting EVs as a novel vaccine strategy. EVs present a low basal immunogenic profile and engineered EVs represent a safe, flexible, and efficient strategy for a virus-free vaccine design. Some biotech companies are developing EV-based vaccines against COVID-19, by displaying the SARS-CoV-2 Spike protein on the exosome surface or by delivering mRNAs of viral proteins through EVs. Extracellular vesicles (EVs) are secreted from almost all human cells and mediate intercellular communication by transferring heterogeneous molecules (i.e., DNA, RNAs, proteins, and lipids). In this way, EVs participate in various biological processes, including immune responses. Viruses can hijack EV biogenesis systems for their dissemination, while EVs from infected cells can transfer viral proteins to uninfected cells and to immune cells in order to mask the infection or to trigger a response. Several studies have highlighted the role of native or engineered EVs in the induction of B cell and CD8(+) T cell reactions against viral proteins, strongly suggesting these antigen-presenting EVs as a novel strategy for vaccine design, including the emerging COVID-19. EV-based vaccines overcome some limitations of conventional vaccines and introduce novel unique characteristics useful in vaccine design, including higher bio-safety and efficiency as antigen-presenting systems and as adjuvants. Here, we review the state-of-the-art for antiviral EV-based vaccines, including the ongoing projects of some biotech companies in the development of EV-based vaccines for SARS-CoV-2. Finally, we discuss the limits for further development of this promising class of therapeutic agents. [ABSTRACT FROM AUTHOR]