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Abstract Cancer immunotherapy aims to initiate or amplify immune responses that eliminate cancer cells and create immune memory to prevent relapse. Immune checkpoint inhibitors (ICIs), which target coinhibitory receptors on immune effector cells, such as CTLA-4 and PD-(L)1, have made significant strides in cancer treatment. However, they still face challenges in achieving widespread and durable responses. The effectiveness of anticancer immunity, which is determined by the interplay of coinhibitory and costimulatory signals in tumor-infiltrating immune cells, highlights the potential of costimulatory receptors as key targets for immunotherapy. This review explores our current understanding of the functions of CD2 and CD226, placing a special emphasis on their potential as novel agonist targets for cancer immunotherapy. CD2 and CD226, which are present mainly on T and NK cells, serve important functions in cell adhesion and recognition. These molecules are now recognized for their costimulatory benefits, particularly in the context of overcoming T-cell exhaustion and boosting antitumor responses. The importance of CD226, especially in anti-TIGIT therapy, along with the CD2‒CD58 axis in overcoming resistance to ICI or chimeric antigen receptor (CAR) T-cell therapies provides valuable insights into advancing beyond the current barriers of cancer immunotherapy, underscoring their promise as targets for novel agonist therapy.

Abstract Although proteomics is extensively used in immune research, there is currently no publicly accessible spectral assay library for the comprehensive proteome of immune cells. This study generated spectral assay libraries for five human immune cell lines and four primary immune cells: CD4 T, CD8 T, natural killer (NK) cells, and B cells. This was achieved by utilizing data-dependent acquisition (DDA) and employing fractionated samples from over 100 µg of proteins, which was applied to acquire the highest-quality MS/MS spectral data. In addition, Data-indedendent acquisition (DIA) was used to obtain sufficient data points for analyzing proteins from 10,000 primary CD4 T, CD8 T, NK, and B cells. The immune cell spectral assay library generated included 10,544 protein groups and 127,106 peptides. The proteomic profiles of 10,000 primary human immune cells obtained from 15 healthy volunteers analyzed using DIA revealed the highest heterogeneity of B cells among other immune cell types and the similarity between CD4 T and CD8 T cells. All data and spectral library are deposited in ProteomeXchange (PXD047742).

Abstract Background Immunotherapy has significantly advanced cancer treatments, but many patients do not respond to it, partly due to immunosuppressive mechanisms used by tumor cells. These cells employ immunosuppressive ligands to evade detection and elimination by the immune system. Therefore, the discovery and characterization of novel immunosuppressive ligands that facilitate immune evasion are crucial for developing more potent anti-cancer therapies. Methods We conducted gain-of-function screens using a CRISPRa (CRISPR activation) library that covered the entire human transmembrane sub-genome to identify surface molecules capable of hindering NK-mediated cytotoxicity. The immunosuppressive role and mechanism of MUC21 were validated using NK and T cell mediated cytotoxicity assays. Bioinformatics tools were employed to assess the clinical implications of mucin-21 (MUC21) in cancer cell immunity. Results Our genetic screens revealed that MUC21 expression on cancer cell surfaces inhibits both the cytotoxic activity of NK cells and antibody-dependent cellular cytotoxicity, but not affecting complement-dependent cytotoxicity. Additionally, MUC21 expression hinders T cell activation by impeding antigen recognition, thereby diminishing the effectiveness of the immune checkpoint inhibitor, anti-PD-L1. Moreover, MUC21 expression suppress the antitumor function of both CAR-T cells and CAR-NK cells. Mechanistically, MUC21 facilitates immune evasion by creating steric hindrance, preventing interactions between cancer and immune cells. Bioinformatics analysis revealed elevated MUC21 expression in lung cancer, which correlated with reduced infiltration and activation of cytotoxic immune cells. Intriguingly, MUC21 expression was higher in non-small cell lung cancer (NSCLC) tumors that were non-responsive to anti-PD-(L)1 treatment compared to responsive tumors. Conclusions These findings indicate that surface MUC21 serves as a potent immunosuppressive ligand, shielding cancer cells from NK and CD8+T cell attacks. This suggests that inhibiting MUC21 could be a promising strategy to improve cancer immunotherapy.

Abstract Adoptive cell therapy (ACT) with antigen‐specific T cells is a promising treatment approach for solid cancers. Interleukin‐2 (IL‐2) has been utilized in boosting the efficacy of ACT. However, the clinical applications of IL‐2 in combination with ACT is greatly limited by short exposure and high toxicities. Herein, a complex coacervate was designed to intratumorally deliver IL‐2 in a sustained manner and protect against proteolysis. The complex coacervate consisted of fucoidan, a specific IL‐2 binding glycosaminoglycan, and poly‐l‐lysine, a cationic counterpart (FPC2). IL‐2‐laden FPC2 exhibited a preferential bioactivity in ex vivo expansion of CD8+T cells over Treg cells. Additionally, FPC2 was embedded in pH modulating injectable gel (FPC2‐IG) to endure the acidic tumor microenvironment. A single intratumoral administration of FPC2‐IG‐IL‐2 increased expansion of tumor‐infiltrating cytotoxic lymphocytes and reduced frequencies of myeloid populations. Notably, the activation and persistency of tumor‐reactive T cells were observed only in the tumor site, not in the spleen, confirming a localized effect of FPC2‐IG‐IL‐2. The immune‐favorable tumor microenvironment induced by FPC2‐IG‐IL‐2 enabled adoptively transferred TCR‐engineered T cells to effectively eradicate tumors. FPC2‐IG delivery system is a promising strategy for T‐cell‐based immunotherapies.

Immune checkpoint inhibitor therapy has proven efficacy in a subset of colon cancer patients featuring a deficient DNA mismatch repair system or a high microsatellite instability profile. However, there is high demand for more effective biomarkers to expand the colon cancer population responding to ICI therapy. PBK/TOPK, a serine/threonine kinase, plays a role in cell cycle regulation and mitotic progression. Here, we investigated the correlation between PBK/TOPK expression and tumor immunity and its prognostic value in colon cancer. Based on large-scale bioinformatics analysis, we discovered that elevated PBK/TOPK expression predicted a favorable outcome in patients with colon cancer and was positively associated with immune infiltration levels of CD8+ T cells, CD4+ T cells, natural killer cells, and M1 macrophages. In contrast, a negative correlation was found between PBK/TOPK expression and immune suppressor cells, including regulatory T cells and M2 macrophages. Furthermore, the expression of PBK/TOPK was correlated with the expression of T-cell cytotoxicity genes in colon cancer. Additionally, high PBK/TOPK expression was associated with mutations in DNA damage repair genes, and thus with increased tumor mutation and neoantigen burden. These findings suggest that PBK/TOPK may serve as a prognostic and predictive biomarker for immunotherapy in colon cancer.

The mucin (MUC) family is a group of highly glycosylated macromolecules that are abundantly expressed in mammalian epithelial cells. MUC proteins contribute to the formation of the mucus barrier and thus have protective functions against infection. Interestingly, some MUC proteins are aberrantly expressed in cancer cells and are involved in cancer development and progression, including cell growth, proliferation, the inhibition of apoptosis, chemoresistance, metabolic reprogramming, and immune evasion. With their unique biological and structural features, MUC proteins have been considered promising therapeutic targets and also biomarkers for human cancer. In this review, we discuss the biological roles of the transmembrane mucins MUC1 and MUC16 in the context of hallmarks of cancer and current efforts to develop MUC1- and MUC16-targeted therapies.

Purpose - The centralized processes of today’s power trading systems are complex and pose a risk of price tampering and hacking. The decentralized and unmodifiable nature of the blockchain technology that has recently been highlighted offers the potential to improve this power trading process. The purpose of this study is to implement a system to apply the blockchain technology to the problem of power trading. Design/methodology/approach - The authors modeled the power trading problem as the interaction between admin, producer and consumer nodes. And a power trading scenario has been created for this model using a blockchain platform called Multichain which is both fast and highly scalable. To verify this scenario, they implemented a trading system using Savoir, a Python-based JsonRPC module. Findings - Experimental results show that all processes, such as blockchain creation, node connectivity, asset issuance and exchange transactions have been correctly handled according to the scenario. Originality/value - In this study, the authors have proposed and implemented a power trading method that determines price according to the pure market principle and cannot be manipulated or hacked. It is based on the nature of blockchain technology that is decentralized and cannot be tampered.

Highly accumulated hyaluronan (HA) not only provides a physiological barrier but also supports an immune-suppressive tumour microenvironment. High-molecular-weight (HMW)-HA inhibits the activation of immune cells and their access into tumour tissues, whereas, low-molecular-weight oligo-HA is known to potentially activate dendritic cells (DCs). In this paper, we investigated whether small extracellular vesicle (EVs)-PH20 hyaluronidase induces tumour HA degradation, which, in turn, activates DCs to promote anti-cancer immune responses. Informed by our previous work, we used a small EV carrying GPI-anchored PH20 hyaluronidase (Exo-PH20) that could deeply penetrate into tumour foci via HA degradation. We found that Exo-PH20-treatment successfully activates the maturation and migration of DCs in vivo, particularly CD103+ DCs leading to the activation of tumour-specific CD8+ T cells, which work together to inhibit tumour growth. Moreover, combination with anti-PD-L1 antibody provided potent tumour-specific CD8+ T cell immune responses as well as elicited prominent tumour growth inhibition both in syngenic and spontaneous breast cancer models, and this anti-tumour immunity was durable. Together, these results present new insights for HA degradation by Exo-PH20, providing a better understanding of oligo HA-triggered immune responses to cancer.

Tumors escape immune surveillance by inducing various immunosuppressive pathways, including the activation of inhibitory receptors on tumor-infiltrating T cells. While monoclonal antibodies (mAbs) blocking programmed cell death 1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) have been approved for multiple cancer indications, only a subset of patients benefit from immune checkpoint blockade therapies, highlighting the need for additional approaches. Therefore, the identification of new target molecules acting in distinct or complementary pathways in monotherapy or combination therapy with PD-1/PD-L1 blockade is gaining immense interest. T cell immunoreceptor with Ig and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains (TIGIT) has received considerable attention in cancer immunotherapy. Recently, anti-TIGIT mAb (tiragolumab) has demonstrated promising clinical efficacy in non-small cell lung cancer treatment when combined with an anti-PD-L1 drug (Tecentriq), leading to phase III trial initiation. TIGIT is expressed mainly on T and natural killer cells; it functions as an inhibitory checkpoint receptor, thereby limiting adaptive and innate immunity. CD226 competes for binding with the same ligands with TIGIT but delivers a positive stimulatory signal to the immune cells. This review discusses the recent discoveries regarding the roles of TIGIT and CD226 in immune cell function and their potential application in cancer immunotherapy.

Childhood and adolescence are critical periods that affect adults’ health status. Therefore, the factors influencing the health of children and adolescents should be analyzed. In Korea, a wide range of youth-related health data has been obtained, both on the regional level and on the national level. This report summarizes the current status of studies related to the health of Korean children and adolescents. Data for which open access is offered include the Korea Youth Risk Behavior Web-based Study, the Panel Study on Korean Children, the Korean Youth Panel Survey, the Korean Children and Youth Panel Survey, and the Student Health Examination. In addition, the Health Examination of Korean Youth Outside of School, the Korean Children and Adolescents Obesity Cohort Study, the Korean Children’s Environmental Health Study, the Korea Youth Media Use and Harmful Environment Survey, the Comprehensive Survey of Korean Youth, and the Multicultural Adolescents Panel Study are summarized.

Immune checkpoint inhibition shows promise for cancer treatment, but only a minority of patients respond. Combination strategies have been explored to overcome this resistance. Combining immunogenic clearance using immunogenic cell death inducers with a rho kinase inhibitor enhances phagocytosis of immunogenically dying cancer cells by antigen-presenting cells, stimulating tumor-specific immune responses by activating CD8+ T cells via dendritic cell-mediated priming. This approach increases the responsiveness of immune checkpoint blockade (ICB)-resistant cancer to ICB. However, the precise mechanisms remain unclear. This study elucidates cellular mechanisms of immunogenic clearance enhancing ICB response. Using single-cell RNA sequencing, we observed an increase in effector memory-like CD8+ T cells within the tumor microenvironment with combined treatment. We propose this cell cluster may originate from proliferating CD8+ T cells elevated by immunogenic clearance. Notably, abundant effector memory-like CD8+ T cells in ICB-responsive patients suggest their antitumor effect. Thus, increasing this cell population through enhanced T cell priming may improve the response of ICB-resistant tumors.

Cervical cancer is a well-known preventable cancer worldwide. Many countries including Korea have pursued the positive endpoint of a reduction in mortality from cervical cancer. Our aim is to examine changing trends in cervical cancer incidence and mortality after the implementation of a national preventive effort in Korea. Cervical cancer incidence data from 1999 to 2011 and mortality data from 1983 to 2013 were collected from the Korean Statistical Information Service. Yearly age-standardized rates (ASR) per 100,000 were compared using two standards: the 2005 Korean population and the world standard population, based on Segi’s world standard for incidence and the World Health Organization for mortality. In Korea, the age-standardized incidence of cervical cancer per 100,000 persons declined from 17.2 in 2000 to 11.8 in 2011. However, the group aged 25 to 29 showed a higher rate in 2011 (ASR, 6.5) than in 2000 (ASR, 3.6). The age-standardized mortality rate per 100,000 persons dropped from 2.81 in 2000 to 1.95 in 2013. In the worldwide comparison, the incidence rates remained close to the average incidence estimate of more developed regions (ASR, 9.9). The decreasing mortality trend in Korea approached the lower rate observed in Australia (ASR, 1.4) in 2010. Although the incidence rate of cervical cancer is continuously declining in Korea, it is still high relative to other countries. Moreover, incidence and mortality rates in females aged 30 years or under have recently increased. It is necessary to develop effective policy to reduce both incidence and mortality, particularly in younger age groups.

The demand for biosensing systems that accurately detect physiological signals and disease biomarkers while maintaining biocompatible surfaces drives ongoing research into advanced materials and novel designs. Wearable patch-based sensors have emerged as a promising solution for effective sweat management, offering easy induction, reliable collection, and precise analysis. This review systematically explores recent advancements in wearable sweat-sensing patches (WSPs) for personalized healthcare monitoring, highlighting their value in non-invasive and continuous health tracking. While recent reviews on wearable sweat sensing have provided general overviews of sweat sensing technologies, this review focuses on the integration of WSPs with emerging fields like flexible human-machine interfaces and smart healthcare solutions, addressing specific technical challenges and innovative approaches that distinguish current advancements. It provides a thorough analysis of key components, including structural materials, sensing mechanisms, innovative sweat collection techniques, and optimal attachment strategies. Additionally, the review addresses challenges and emerging trends, offering a pathway for integrating WSPs into flexible human-machine interfaces, personalized healthcare solutions, and closed-loop systems.

Purpose: Patients experience severe physical trauma every year. However, studies on survivors’ experiences after severe injury are limited. Previous studies have mainly focused on time spans of trauma treatment. This study aimed to comprehensively explore survivors’ experiences to improve the current quality of trauma treatment and highlight the importance of patient-centered care. Materials and Methods: Structured, face-to-face interviews with six domains were conducted on survivors aged ≥18 years who were previously hospitalized in an intensive care unit due to traumatic injuries. Self-reported questionnaires were administered for a multidimensional assessment of participants’ conditions. Transcripts of each narrative were analyzed per grounded theory. Results: Fourteen participants were assessed. The median injury severity score was 25.5. The median elapsed time from injury to interview was 17.3 months. The physical and psychiatric difficulties of the participants remained unresolved even after completing rehabilitation. The main theme derived from the narratives were struggle with injury, consequences, and contributing factors, with the following subthemes: 1) suffering from injury and treatment, 2) psychological adaptation to the changed self and life after the accident, 3) significant family support, 4) gratitude to medical staff despite inadequacies in the healthcare system, and 5) legal and economic issues that impede recovery. Conclusion: Increased efforts focusing on enabling survivors of severe injury to return to society and improve their quality of life are needed, including the establishment of patient-centered care in the trauma field, extended care for the survivors’ families, multidisciplinary treatment, and the collection of quantitative post-discharge data. [ABSTRACT FROM AUTHOR]

Efficient lithium recovery from geothermal brines is crucial for the battery industry. Current electrochemical separation methods struggle with the simultaneous presence of Na+, K+, Mg2+, and Ca2+ because these cations are similar to Li+, making it challenging to separate effectively. We address these challenges with a three-chamber reactor featuring a polymer porous solid electrolyte in the middle layer. This design improves the transference number of Li+ (tLi+) by 2.1 times compared to the two-chamber reactor and also reduces the chlorine evolution reaction, a common side reaction in electrochemical lithium extraction, to only 6.4% in Faradaic Efficiency. Employing a lithium-ion conductive glass ceramic (LICGC) membrane, the reactor achieved high tLi+ of 97.5% in LiOH production from simulated brine, while the concentrations of Na+ K+, Mg2+, and Ca2+ are below the detection limit. Electrochemical experiments and surface analysis elucidated the cation transport mechanism, highlighting the impact of Na+ on Li+ migration at the LICGC interface. [ABSTRACT FROM AUTHOR]

The fundamental tradeoff has made it difficult to enhance the low permittivity of wide bandgap semiconductors without sacrificing the bandgap. In this work we demonstrate that high-concentration substitutional Be doping can enhance NiO’s dielectric properties and simultaneously widen the bandgap. Up to 5 at% of Ni in NiO could be substituted by Be while maintaining the rocksalt crystalline structure. The real part of permittivity at low frequencies was found to be significantly increases (40%) while bandgap also increases from 3.06 to 3.37. These findings offer engineering insights for developing high-K wide bandgap materials, essential for various electronic and optoelectronic applications.

SMARCA4 (BRG1) is a core unit of the SWI/SNF complex, regulating gene transcription through chromatin remodeling. Germline SMARCA4 variants have been reported to be associated with various malignancies. Here, we report the first case of extraskeletal Ewing sarcoma in a young female patient with a germline pathogenic variant of SMARCA4 (c.3546 + 1G>A), diagnosed with next generation sequencing (NGS). This alteration was also identified in her familial lineage, including her sister who was previously diagnosed with small cell carcinoma of the ovary, hypercalcemic type, a malignancy highly associated with SMARCA4 mutations. Despite undergoing radical surgery and receiving systemic treatments including VeIP (vinblastine, ifosfamide, cisplatin), and VDC (vincristine, doxorubicin, cyclophosphamide) regimens, the patient succumbed to death due to disease progression. With the implementation of NGS, we anticipate that more cases with SMARCA4 mutations will be diagnosed in the future. Further research is necessary to unveil therapeutic targets associated for this oncogenic alteration. [ABSTRACT FROM AUTHOR]

This guideline aims to promote the prudent use of antibacterial agents for managing carbapenem-resistant Enterobacterales (CRE) infections in clinical practice in Korea. The general section encompasses recommendations for the management of common CRE infections and diagnostics, whereas each specific section is structured with key questions that are focused on antibacterial agents and disease-specific approaches. This guideline covers both currently available and upcoming antibacterial agents in Korea. [ABSTRACT FROM AUTHOR]

Objective: Patients with ovarian cancer have a high risk of developing thrombosis. We aimed to investigate laboratory parameters associated with deep vein thrombosis (DVT) in patients treated for ovarian cancer. Methods: We retrospectively analyzed pre-operation laboratory data of patients with ovarian cancer for DVT at the National Cancer Center, Korea, between January 2000 and February 2021. The test items were white blood cell count, absolute neutrophil count (ANC), hemoglobin, platelets, monocytes, serum glucose, CA125, D-dimer, fibrinogen, prothrombin time (PT), activated partial thromboplastin time (aPTT), and body mass index (BMI). Differences between patients with and without DVT were compared with Wilcoxon rank-sum test. We analyzed the variables using logistic regression. Items with significant odds ratios were included in multivariate logistic regression. Significant variables were selected using backward elimination. Items were further categorized based on reference ranges. Univariate and multivariate analyses were performed to identify items with abnormal values associated with DVT. Results: From 3,147 patient samples analyzed, 286 (9.1%) patients with DVT were selected. Differences between patients with vs without DVT were statistically significant for hemoglobin, monocyte, serum glucose, CA125, PT, aPTT, fibrinogen, D-dimer, and BMI. After univariate and multivariate analysis, monocyte, glucose, and PT remained significant. Among the categorical variables, low hemoglobin, high monocyte, high CA125, prolonged PT, and high BMI remained significant after univariate and multivariate analysis. Conclusion: Pre-operation laboratory data of low hemoglobin, high monocyte percentage, high serum glucose, high CA125, prolonged PT, and high BMI were associated with DVT. [ABSTRACT FROM AUTHOR]