Human γδ T cells in the tumor microenvironment: Key insights for advancing cancer immunotherapy.

The role of γδ T cells in antitumor responses has gained significant attention due to their unique major histocompatibility complex (MHC)-independent killing mechanisms, which distinguish them from conventional αβ T cells. Notably, γδ tumor-infiltrating lymphocytes (TILs) have been identified as favorable prognostic markers in various cancers. However, γδ TIL subsets, including Vδ1, Vδ2, and Vδ3, exhibit distinct prognostic implications and phenotypes from one another within the tumor microenvironment (TME).

Type I interferon signaling regulates myeloid and T cell crosstalk in the glioblastoma tumor microenvironment.

Downstream interferon signaling through the type I interferon (IFN) receptor, IFNAR, is crucial for the proper production of type I IFNs in mounting anti-tumor immune responses. Our study investigates the role of type I IFN signaling in the glioblastoma (GBM) tumor microenvironment by leveraging single-cell RNA sequencing to analyze tumor-infiltrating lymphocytes. We investigate how type I IFN signaling within the myeloid compartment contributes to the crosstalk with T cells in the tumor microenvironment.

Engineering interferons for cancer immunotherapy.

Interferons are a family of cytokines that are famously known for their involvement in innate and adaptive immunity. Type I interferons (IFNs) exert pleiotropic effects on various immune cells and contribute to tumor-intrinsic and extrinsic mechanisms. Their pleiotropic effects and ubiquitous expression on nucleated cells have made them attractive candidates for cytokine engineering to deliver to largely immunosuppressive tumors.

Assessment of immunopathological responses of a novel non-chemical biocide in C57BL/6 for safe disinfection usage.

Background: Water electrospray technology has been developed and extensively studied for its physical properties and potential application as a non-chemical biocide against airborne pathogens. However, there are still concerns regarding the safety and potential toxicity of inhaling water electrospray (WE) particles. To address these potential hazards and offer insights into the impact of WE on humans, we analyzed the immunopathological response to WE by employing an intranasal challenge C57BL/6 mouse model.

Targeted Liposomal Co-delivery of an Immunogenic Cell Death Inducer and a Toll-Like Receptor 4 Agonist for Enhanced Cancer Chemo-immunotherapy.

Anticancer chemo-immunotherapy has gained considerable attention across various scientific domains as a prospective approach for the comprehensive eradication of malignant tumors. Recent research has particularly been focused on traditional anthracycline chemo drugs, such as doxorubicin and mitoxantrone. These compounds trigger apoptosis in tumor cells and evoke immunogenic cell death (ICD).

Microbiome dynamics in immune checkpoint blockade.

Immune checkpoint blockade (ICB) is one of the leading immunotherapies, although a variable extent of resistance has been observed among patients and across cancer types. Among the efforts underway to overcome this challenge, the microbiome has emerged as a factor affecting the responsiveness and efficacy of ICB. Active research, facilitated by advances in sequencing techniques, is assessing the predominant influence of the intestinal microbiome, as well as the effects of the presence of an intratumoral microbiome.

γδ T cells as a potential therapeutic agent for glioblastoma.

Although γδ T cells comprise a small population of T cells, they perform important roles in protecting against infection and suppressing tumors. With their distinct tissue-localizing properties, combined with their various target recognition mechanisms, γδ T cells have the potential to become an effective solution for tumors that do not respond to current therapeutic procedures. One such tumor, glioblastoma (GBM), is a malignant brain tumor with the highest World Health Organization grade and therefore the worst prognosis.

Supplementation with a high-glucose drink stimulates anti-tumor immune responses to glioblastoma via gut microbiota modulation.

A high-sugar diet induces lifestyle-associated metabolic diseases, such as obesity and diabetes, which may underlie the pro-tumor effects of a high-sugar diet. We supply GL261 syngeneic glioblastoma (GBM) mice with a short-term high-glucose drink (HGD) and find an increased survival rate with no evidence of metabolic disease. Modulation of the gut microbiota through HGD supplementation is critical for enhancing the anti-tumor immune response.

Double-edged sword: γδ T cells in mucosal homeostasis and disease.

The mucosa is a tissue that covers numerous body surfaces, including the respiratory tract, digestive tract, eye, and urogenital tract. Mucosa is in direct contact with pathogens, and γδ T cells perform various roles in the tissue. γδ T cells efficiently defend the mucosa from various pathogens, such as viruses, bacteria, and fungi.

Intranasal delivery of an adenovirus-vector vaccine co-expressing a modified spike protein and a genetic adjuvant confers lasting mucosal immunity against SARS-CoV-2.

The ongoing COVID-19 pandemic caused by SARS-CoV-2 infection has threatened global health. Since the first case of infection was reported in December 2019, SARS-CoV-2 has rapidly spread worldwide and caused millions of deaths. As vaccination is the best way to protect the host from invading pathogens, several vaccines have been developed to prevent the infection of SARS-CoV-2, saving numerous lives thus far.

Harnessing type I interferon-mediated immunity to target malignant brain tumors.

Type I interferons have long been appreciated as a cytokine family that regulates antiviral immunity. Recently, their role in eliciting antitumor immune responses has gained increasing attention. Within the immunosuppressive tumor microenvironment (TME), interferons stimulate tumor-infiltrating lymphocytes to promote immune clearance and essentially reshape a "cold" TME into an immune-activating "hot" TME.

Protocol for analyzing γδ T cells from the vagina of diet-induced obese mice using single-cell RNA sequencing and flow cytometry.

Obesity affects susceptibility to sexually transmitted diseases like genital herpes, caused by herpes simplex virus (HSV) 2. The γδ T cells in the vagina play a major role in HSV-2 suppression. Here, we present a protocol for inducing HSV-2 infection intravaginally in high-fat diet-induced obese mice.

Regulation of c-SMAC formation and AKT-mTOR signaling by the TSG101-IFT20 axis in CD4 T cells.

CD4 T cells play major roles in the adaptive immune system, which requires antigen recognition, costimulation, and cytokines for its elaborate orchestration. Recent studies have provided new insight into the importance of the supramolecular activation cluster (SMAC), which comprises concentric circles and is involved in the amplification of CD4 T cell activation. However, the underlying mechanism of SMAC formation remains poorly understood.

The Role of Hypoxia in Brain Tumor Immune Responses.

Oxygen is a vital component of living cells. Low levels of oxygen in body tissues, known as hypoxia, can affect multiple cellular functions across a variety of cell types and are a hallmark of brain tumors. In the tumor microenvironment, abnormal vasculature and enhanced oxygen consumption by tumor cells induce broad hypoxia that affects not only tumor cell characteristics but also the antitumor immune system.

Pellino-1 promotes intrinsic activation of skin-resident IL-17A-producing T cells in psoriasis.

Background: Psoriasis is a chronically relapsing inflammatory skin disease primarily perpetuated by skin-resident IL-17-producing T (T17) cells. Pellino-1 (Peli1) belongs to a member of E3 ubiquitin ligase mediating immune receptor signaling cascades, including nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB) pathway.

Objective: We explored the potential role of Peli1 in psoriatic inflammation in the context of skin-resident T17 cells.

The immune landscape of high-grade brain tumor after treatment with immune checkpoint blockade.

Despite the therapeutic success of immune checkpoint blockade (ICB) therapy against multiple tumors, many patients still do not benefit from ICB. In particular, high-grade brain tumors, such as glioblastoma multiforme (GBM), have a very low response rate to ICB, resulting in several failed clinical trials. This low response rate might be caused by a lack of understanding of the unique characteristics of brain immunity.

Obesity enhances antiviral immunity in the genital mucosa through a microbiota-mediated effect on γδ T cells.

Obesity is detrimental to the immune system. It impairs lymphatics, T cell development, and lymphopoiesis; induces dysfunction of antitumor immunity; and also promotes tumor progression. However, direct evidence of the impact of obesity on viral infection is lacking.

Human allogenic γδ T cells kill patient-derived glioblastoma cells expressing high levels of DNAM-1 ligands.

Adoptive transfer of γδ T cells is a novel immunotherapeutic approach to glioblastoma. Few recent studies have shown the efficacy of γδ T cells against glioblastoma, but no previous studies have identified the ligand-receptor interactions between γδ T cells and glioblastoma cells. Here, we identify those ligand-receptor interactions and provide a basis for using γδ T cells to treat glioblastoma.

Blood monocyte-derived CD169 macrophages contribute to antitumor immunity against glioblastoma.

Infiltrating tumor-associated macrophages (TAM) are known to impede immunotherapy against glioblastoma (GBM), however, TAMs are heterogeneous, and there are no clear markers to distinguish immunosuppressive and potentially immune-activating populations. Here we identify a subset of CD169 macrophages promoting an anti-tumoral microenvironment in GBM. Using single-cell transcriptome analysis, we find that CD169 macrophages in human and mouse gliomas produce pro-inflammatory chemokines, leading to the accumulation of T cells and NK cells.

Frame-rate up-conversion detection based on convolutional neural network for learning spatiotemporal features.

With the advance in user-friendly and powerful video editing tools, anyone can easily manipulate videos without leaving prominent visual traces. Frame-rate up-conversion (FRUC), a representative temporal-domain operation, increases the motion continuity of videos with a lower frame-rate and is used by malicious counterfeiters in video tampering such as generating fake frame-rate video without improving the quality or mixing temporally spliced videos. FRUC is based on frame interpolation schemes and subtle artifacts that remain in interpolated frames are often difficult to distinguish.

Protocol to analyze antitumor immunity of orthotopic injection and spontaneous murine high-grade glioma models using flow cytometry and single-cell RNA sequencing.

Despite the recognized importance of antitumor immunity, our understanding of brain tumor immunity is poor. Orthotopic injection models have been widely used for immunological analyses. However, these models have limitations in analysis of antitumor immunity because the approach involves drilling skulls and injecting tumor cells, which can induce adverse effects.

Host and Microbiome Interplay Shapes the Vaginal Microenvironment.

The female reproductive tract harbors a unique microbiome, especially the vagina. The human vaginal microbiome exhibits a low diversity and is dominated by species, compared to the microbiome of other organs. The host and vaginal microbiome mutually coexist in the vaginal microenvironment.

Dendritic Cell-Based Immunotherapy in Hot and Cold Tumors.

Dendritic cells mediate innate and adaptive immune responses and are directly involved in the activation of cytotoxic T lymphocytes that kill tumor cells. Dendritic cell-based cancer immunotherapy has clinical benefits. Dendritic cell subsets are diverse, and tumors can be hot or cold, depending on their immunogenicity; this heterogeneity affects the success of dendritic cell-based immunotherapy.

A Microbiota-Dependent Subset of Skin Macrophages Protects Against Cutaneous Bacterial Infection.

Microbiota is essential to the development and functional maturation of the immune system. The effects of the gut microbiota on myeloid cells remote from the gut, especially the skin remain unclear. Transcriptomic analysis revealed that type I interferon (IFN) signaling was down-regulated in the skin of germ-free mice compared to that in specific pathogen-free mice.