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Cytotoxic CD4+ T cells in cancer: an emerging target for next-generation anticancer immunotherapy?

Over the last decades, a growing number of distinct CD4+T helper cells has been identified and our understanding of CD4+T cell differentiati … ancer types. These cells have the ability to secrete cytotoxic molecules and kill target cells in a major histocompatibility complex (MHC) class II-dependent manner. In this review, we give an overview of phenotypical characteristics of CD4+CTLs in human cancers and the antitumor mechanisms employed by these cells. Further, we explore their role and clinical relevance in the cont …

Pattern Recognition by NOD-Like Receptors.

Nucleotide-binding oligomerization domain-like receptors (NLRs) are a family of cytosolic pattern recognition receptors (PRRs) and able to r … with other PRRs but some NLRs directly modulate adaptive immunity via transcriptional regulation of major histocompatibility complex (MHC) class I and class II. NLRs have an essential role as intracellular PRRs and thereby orchestrate inflammatory responses. NLR mutations and subsequent dysfunction can result in cancer or autoinflammatory diseases, such as Crohn's disease and ulc …

Targeting gut microbiota and arginase boosts MEK inhibitors' enhancement of antitumour immunity via MHC-I upregulation in colorectal cancer.

BACKGROUND: Elevating major histocompatibility complex class I (MHC-I) levels in tumour cells can boost antitumour immunity and enhance immunotherapy for colorectal cancer (CRC). Screening an FDA-approved drug library showed that MEK inhibitors (MEKis) significantly increase MHC-I expression in CRC cells, though the mechanisms and antitumour effects of MEKis, as well as their impact on gut microbiota, remain unclear. METHODS: Dual-luciferase reporter system was employed to screen MHC-I inducers. MHC-I expression was analysed using qRT-PCR, flow cytometry, and western blot. OT-I TCR transgenic…

Recent advances in tumor immunotherapy based on NK cells.

Immunotherapy has emerged as the established fourth pillar of cancer treatment following surgery, radiotherapy, and chemotherapy, representing a cutting-edge research domain in translational medicine and clinical oncology. Natural killer (NK) cells, a type of innate cytotoxic lymphocyte, possess unique antitumor properties that are independent of major histocompatibility complex (MHC) restrictions, making them promising candidates for "off-the-shelf" therapeutic products. NK cells can eliminate tumor cells through various mechanisms. Genetic engineering of NK cells can enhance their activation…

Melanoma MHC-I-membrane-encapsulated Cu@ferrihydrite induces ferroptosis/cuproptosis and systematic immunity against tumor.

Major histocompatibility complex I (MHC-I) has significant potential for augmenting cancer immunogenicity and immune recognition. Here, we report an innovative therapeutic strategy that synergistically integrates blue light-upregulated MHC-I expression with blue light-induced ferroptosis and cuproptosis. Blue light promoted MHC-I expression in mouse melanoma cells by modulating the NF-κB-SUSD6 signaling axis. Subsequently, an MHC-I-enriched melanoma cytomembrane was used to encapsulate the photoresponsive Cu@ferrihydrite (Cu@Fh) nanoparticles, forming M-Cu@Fh. MHC-I facilitated dendritic cells…

PRRSV interaction with the adaptive immune system of host: an update review.

Porcine reproductive and respiratory syndrome virus (PRRSV), a highly variable RNA virus, causes a significant threat to the global swine in … mmunity through multiple mechanisms, including down-regulating antigen-presenting molecules such as major histocompatibility complex class (MHC) -I/II, inducing immunosuppressive microenvironments such as up-regulating interleukin-10 (IL-10) and Programmed Death-Ligand 1 (PD-L1), and interfering with the generation of neutralizing antibodies, thereby weakening the host's antivira …

HLA-DQB1-mediated B cell-epithelial crosstalk drives EBV-associated inflammation in Hunner-type interstitial cystitis.

Hunner-type interstitial cystitis (HIC) is a chronic condition marked by persistent pain and inflammation. To elucidate its immunogenetic drivers, we integrated bulk RNA sequencing and single-cell RNA sequencing datasets with targeted major histocompatibility complex (MHC) sequencing. Transcriptomic analysis revealed selective expansion of B cells and epithelial cells, with strong enrichment of Epstein-Barr virus (EBV) response signatures. CellChat and NicheNet modeling uncovered bidirectional communication wherein B cells secrete IL-1β, FGF2, LIF, and TNFSF9, activating prostaglandin synthesi…

Modular activation of macrophage-like cells by beta-2-microglobulin via mitochondria and the cGAS-STING pathway.

Beta-2-microglobulin (β2m) is a component of the major histocompatibility complex class I. β2m is released into cellular fluids in response to various stimuli, including pro-inflammatory cytokines. Elevated β2m levels have been found associated with autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and Crohn's disease, as well as in various hematological cancers and viral infections. Despite an established correlation between immune activation of especially monocytes and macrophages, and circulating β2m levels, the causative relationship remains unclear. Here, we …

Behavioral, cellular, and molecular changes in two animal models of bipolar disorder mania: sleep deprivation-induced mice and Clock-mutant mice.

Sleep disturbances are prevalent in bipolar disorder (BD) patients, and the circadian locomotor output cycles kaput (Clock) gene plays a significant role in this process. The role of microglia (the brain-resident immune cells) in mediating this process remains uncertain. In this study, our findings showed that sleep loss induces mania-like behavior, microglial loss, and time-dependent gene expression changes. Moreover, diurnal oscillations in circadian rhythm-associated and inflammation-related gene expression in the mouse prefrontal cortex (PFC) were altered following sleep deprivation (SD).

Непосредственная инфекция ОХСВ вызывает созревание постоянного тока и терапию опухоли.

Онколитический герпес супервирус (OHSV) является перспективной иммунной терапией рака, которая вызывает лизиз опухолей и стимулирует иммунитет от опухоли. Наша предыдущая одноклеточная последовательность анализа опухолей medulloblasoma, обработанных ОХСВ, выявила расширение и активацию опухолей, проникающих в дендритные клетки (DCs), и прямую инфекцию ОХСВ в мозгу. В то время как терапевтические последствия ОХСТС обусловлены главным образом опухолью клеток, мы предполагаем, что прямая инфекция РС также способствует терапевтической эффективности, поощряя созревание DC и иммунную активацию. Несм

Совпадение в аннотации оригинала
Oncolytic herpes simplex virus (oHSV) is a promising cancer immunotherapy that induces tumor cell lysis and stimulates anti-tumor immunity. … mune activation. Although the oHSV infection in DCs was abortive, it led to increased expression of major histocompatibility complex (MHC) class I/II and co-stimulatory molecules. oHSV-infected DCs activated naïve CD4+ and CD8+ T cells, inducing expression of CD69 and CD25. These primed T cells exhibited enhanced cytotoxicity against CT-2A glioma cells. Adoptive transfer of oHSV- …

NKG2D (Natural Killer Group 2, Member D) ligand expression and ameloblastoma recurrence: a retrospective immunohistological pilot study.

BACKGROUND/PURPOSE: This retrospective immunohistological pilot study aimed to investigate the influence of natural killer group 2, member D (NKG2D) ligand expression on ameloblastoma recurrence after surgical resection. It also aimed to elucidate additional clinical factors that could serve as predictors of ameloblastoma recurrence. MATERIALS AND METHODS: This study included 96 patients who were histologically diagnosed with ameloblastoma after surgical resection. The expression of NKG2D ligands, including UL16-binding proteins (ULBPs) 1-3 and major histocompatibility complex class I chain-r…

Lipocalin-2 expression identifies an intestinal regulatory neutrophil population during acute graft-versus-host disease.

Acute graft-versus-host disease (aGVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT), for … s through the LCN2 receptor SLC22A17, which increased interleukin-10 (IL-10) production and reduced major histocompatibility complex class II (MHCII) expression. Transfer of LCN2-pretreated macrophages reduced aGVHD severity but did not reduce graft-versus-leukemia effects. Furthermore, LCN2 expression correlated with IL-10 expression in intestinal biopsies in multiple cohorts of …

A meta-analysis on the potency of foot-and-mouth disease vaccines in different animal models.

Whether mice can be used as a foot-and-mouth disease (FMD) model has been debated for a long time. However, the major histocompatibility complex between pigs and mice is very different. In this study, the protective effects of FMD vaccines in different animal models were analyzed by a meta-analysis. The databases PubMed, China Knowledge Infrastructure, EMBASE, and Baidu Academic were searched. For this purpose, we evaluated evidence from 14 studies that included 869 animals with FMD vaccines. A random effects model was used to combine effects using Review Manager 5.4 software. A forest plot sh…

Not an immune cell, but they may act like one-cells with immune properties outside the immune system.

The cells presented in this work are not classified as cells that make up the immune system. They, however, present functions and molecules, which are characteristic of immune cells. These characteristic functions are, for example, sensing threat, performing phagocytosis, presentation of foreign antigens, cytokine release or enhancing immune memory. The enlisted immune response mechanisms are carried out by the possession of molecules such as Toll-like receptors, receptors for the Fc fragment of IgG, major histocompatibility complex class II molecules, costimulatory CD80/CD86 proteins and mole…

CD3ζ-Mediated Signaling Protects Retinal Ganglion Cells in Glutamate Excitotoxicity of the Retina.

Excessive levels of glutamate activity could potentially damage and kill neurons. Glutamate excitotoxicity is thought to play a critical role in many CNS and retinal diseases. Accordingly, glutamate excitotoxicity has been used as a model to study neuronal diseases. Immune proteins, such as major histocompatibility complex (MHC) class I molecules and their receptors, play important roles in many neuronal diseases, while T-cell receptors (TCR) are the primary receptors of MHCI. We previously showed that a critical component of TCR, CD3ζ, is expressed by mouse retinal ganglion cells (RGCs). The …

IL-10 modified mRNA monotherapy prolongs survival after composite facial allografting through the induction of mixed chimerism.

Vascularized composite allotransplantation has great potential in face transplantation by supporting functional restoration following tissue … ti-inflammatory environments. We found that without any immunosuppression, C57BL/6J mice with fully major histocompatibility complex (MHC)-mismatched facial allografts and local injection of IL-10 modRNA had a significantly prolonged survival rate. Decreased lymphocyte infiltration and pro-inflammatory T helper 1 subsets and increased anti-inflammatory regulatory T cells (Tregs) …

Efficacy and safety of baricitinib in patients with alopecia areata: evidence to date.

Alopecia areata (AA) is a chronic, tissue-specific autoimmune disorder, characterized by non-scaring hair loss, with a global prevalence of approximately 2%. Typically, it affects a young population, with initial onset frequently occurring before the age of 30 years. Even though the exact pathogenesis of AA remains unclear, the predominant hypothesis is the breakdown of immune privilege of the hair follicle, resulting in increased self-antigen and major histocompatibility complex expression in the follicular epithelium. The relapsing nature of the disease negatively impacts patients' quality o…

Facial attractiveness is only weakly linked to genome-wide heterozygosity.

INTRODUCTION: It has been frequently suggested that overall genomic heterozygosity and, particularly, heterozygosity of loci on the so-called major histocompatibility complex (MHC), which is responsible for the recognition of foreign substances/ pathogens and the recognition of self and non-self, is associated with better health and better resistance to infections and parasites. It has further been speculated that such a potentially beneficial heterozygosity can be detected through body odor and facial attractiveness. METHODS: On the basis of genome wide SNP data (713,014 SNPs) of participant…

Immaturity of immune cells around the dural venous sinuses contributes to viral meningoencephalitis in neonates.

High neonatal susceptibility to meningitis has been attributed to the anatomical barriers that act to protect the central nervous system (CN … he neonatal dural immune cells are immature and predominantly composed of CD206hi macrophages, with major histocompatibility complex class II (MHCII)hi macrophages being rare. In adults, however, perivenous sinus immune cells were enriched in MHCIIhi macrophages that are specialized for producing antiviral molecules and chemokines compared with CD206hi macrophages and protected t …

Variation of Proteolytic Cleavage Sites towards the N-Terminal End of the S2 Subunit of the Novel SARS-CoV-2 Omicron Sublineage BA.2.12.1.

The prevalence of novel SARS-CoV-2 variants is also accompanied by an increased turnover rate and additional cleavage sites at the positions … lusion, such an amino acid substitution modifies S2 antigen processing and might further impact the major histocompatibility complex (MHC) binding and T cell activation.