Hyung-Seok Seo

The recent advent of DNA sequencing technologies facilitates the use of genome sequencing data that provide means for more informative and precise classification and identification of members of the Bacteria and Archaea. Because the current species definition is based on the comparison of genome sequences between type and other strains in a given species, building a genome database with correct taxonomic information is of paramount need to enhance our efforts in exploring prokaryotic diversity a

T cells expressing chimeric antigen receptors (CAR T cells) have shown impressive therapeutic efficacy against leukemias and lymphomas. However, they have not been as effective against solid tumors because they become hyporesponsive (“exhausted” or “dysfunctional”) within the tumor microenvironment, with decreased cytokine production and increased expression of several inhibitory surface receptors. Here we define a transcriptional network that mediates CD8 + T cell exhaustion. We show that the h

During cancer immunoediting, loss of major histocompatibility complex class I (MHC-I) in neoplasm contributes to the evasion of tumours from host immune system. Recent studies have demonstrated that most natural killer (NK) cells that are found in advanced cancers are defective, releasing the malignant MHC-I-deficient tumours from NK-cell-dependent immune control. Here, we show that a natural killer T (NKT)-cell-ligand-loaded tumour-antigen expressing antigen-presenting cell (APC)-based vaccine

Cancer genomes are characterized by focal increases in DNA methylation, co-occurring with widespread hypomethylation. Here, we show that TET loss of function results in a similar genomic footprint. Both 5hmC in wild-type (WT) genomes and DNA hypermethylation in TET -deficient genomes are largely confined to the active euchromatic compartment, consistent with the known functions of TET proteins in DNA demethylation and the known distribution of 5hmC at transcribed genes and active enhancers. In c

Abstract PD-1–based cancer immunotherapy is a successful example of immune checkpoint blockade that provides long-term durable therapeutic effects in patients with cancer across a wide spectrum of cancer types. Accumulating evidence suggests that anti-PD-1 therapy enhances antitumor immunity by reversing the function of exhausted T cells in the tumor environment. However, the responsiveness rate of patients with cancer to anti-PD-1 therapy remains low, providing an urgent need for optimization a

Abstract Increased expression of coinhibitory molecules such as PD-1 and Tim-3 on NK cells has been demonstrated in advanced cancer patients who harbor MHC class I–deficient tumors. However, even in preclinical models, the antitumor effects of checkpoint blockade on NK cells have not been clearly elucidated. Here, we show that anti–PD-1/anti–Tim-3 treatment suppressed tumor progression in mice bearing MHC class I–deficient tumors, and the suppression was further enhanced by recombinant IL21 (rIL

Acute neuroinflammation rapidly activates brain immune responses, but its lasting effects on microglia are unclear. Using systemic LPS administration and LCMV-Armstrong infection, we found that blood-brain barrier disruption and cytokine shifts resolved within 30 days, yet microglial recovery was incomplete-marked by persistent numerical loss and an IFN-γ-low phenotype in the LPS model and reduced relative abundance in the LCMV model. Single-cell RNA sequencing revealed sustained transcriptional

Background: Core body temperature (TC) can decrease during general anesthesia. Particularly in elderly patients, more aggressive strategies to prevent intraoperative hypothermia may be required. Here, we investigated the effect of a heated humidifier on intraoperative TC decrease in the elderly. Methods: Twenty-four elderly patients were randomly assigned into two groups: those who used a heated humidifier (group H) and those who used a conventional ventilator circuit with a heat moisture exchan

Abstract T cells expressing chimeric antigen receptors (CARs) have shown impressive therapeutic efficacy against leukemias and lymphomas, but have not been as effective against solid tumors because chronic stimulation with tumor antigens causes them to enter a hyporesponsive (“exhausted” or “dysfunctional”) state. Here we show that the high-mobility group (HMG)-box transcription factors TOX and TOX2 are highly expressed in CAR-expressing exhausted (PD-1highTim3high) CD8+ tumor-infiltrating lymph

Abstract Adoptive cell therapy with chimeric antigen receptor expressing T (CAR T) cells has shown promising therapeutic efficacy against leukemia and lymphoma. However, CAR T cells in solid tumors fail to be as effective as in liquid tumors since they enter into a hyporesponsive (exhausted or dysfunctional) state that is induced by chronic antigen stimulation in cancer. Here, we show that CAR T cells in solid tumors exhibit low effector function and high expression of inhibitory receptors such