Immunology & Cell Biology最新文献

Natural killer (NK) cells play a vital role in innate immunity and show great promise in cancer immunotherapy. Traditional sources of NK cells, such as the peripheral blood, are limited by availability and donor variability. In addition, in vitro expansion can lead to functional exhaustion and gene editing challenges. This study aimed to harness induced pluripotent stem cell (iPSC) technology to provide a consistent and scalable source of NK cells, overcoming the limitations of traditional sources and enhancing the potential for cancer immunotherapy applications. We developed human placental–derived iPSC lines using reprogramming techniques. Subsequently, an optimized two-step differentiation protocol was introduced to generate high-purity NK cells. Initially, iPSCs were differentiated into hematopoietic-like stem cells using spin-free embryoid bodies (EBs). Subsequently, the EBs were transferred to ultra-low attachment plates to induce NK cell differentiation. iPSC-derived NK (iNK) cells expressed common NK cell markers (NKp46, NKp30, NKp44, CD16 and eomesodermin) at both RNA and protein levels. iNK cells demonstrated significant resilience to cryopreservation and exhibited enhanced cytotoxicity. The incorporation of a chimeric antigen receptor (CAR) construct further augmented their cytotoxic potential. This study exemplifies the feasibility of generating iNK cells with high purity and enhanced functional capabilities, their improved resilience to cryopreservation and the potential to have augmented cytotoxicity through CAR expression. Our findings offer a promising pathway for the development of potential cellular immunotherapies, highlighting the critical role of iPSC technology in overcoming challenges associated with traditional NK cell sources.

Eosinophils have traditionally been viewed as pathological effector cells primarily involved in antiparasitic and allergic immune reactions; however, it is becoming increasingly apparent that eosinophils are multifaceted leukocytes that contribute to a variety of roles in both health and disease. Recent research shows that eosinophils play important immunoregulatory roles across various tissue sites including the gastrointestinal tract, adipose tissue, lung, liver, heart, muscles, thymus and bone marrow. With recent advances in our knowledge and appreciation of eosinophil immunoregulatory functions at these tissue sites, as well as emerging research demonstrating the existence of distinct subsets of eosinophils, a review of this topic is timely. Although some questions remain regarding eosinophil function and heterogeneity, this review summarizes the contemporary understanding of the immunoregulatory roles of eosinophils across various tissues and discusses the latest research on eosinophil heterogeneity and subsets.

In this article, we discuss new findings which suggest that type I regulatory T (Tr1) cells can interfere with cancer vaccine efficacy in mice by exerting strong regulatory control over antitumor immune responses.

This Special Feature explores the fascinating field of Computational Immunology and features reviews on recent immunology research that used computational tools and concepts to understand the nexus of cancer immunology, autoimmunity and host-pathogen interactions.

This Research Highlight discusses a recent publication, where the authors identified an increase in CXCL13⁺ peripheral helper T/follicular helper T cells, which was concomitant with a decrease in CD96⁺ T helper 22 (T_H22) cells in patients with systemic lupus erythematosus. The genetic and epigenetic cues that reciprocally regulate this pathogenic imbalance of T-cell subsets were also identified, thus providing targets for therapeutic intervention.

The interdisciplinary nature of immunology can make studying not only engaging but also challenging, as understanding immunologic processes and immune system components requires foundational knowledge from several science disciplines. The University of Alabama at Birmingham has a unique, 4-year, Undergraduate Immunology Program (UIP) that provides a comprehensive curriculum in immunology that includes five core courses starting in the second year, at which point, students are in the process of completing basic science sequences. For this study, students in courses across the UIP curriculum were asked to identify basic science topics that relate to four immunology concepts. In addition, students were surveyed on their confidence in understanding each of the basic science topics and were asked to identify the course in which they felt that they had fully learned the topic. Data from this study did not demonstrate a change in students' interdisciplinary science competency from the second to fourth year. Importantly, students reported that they fully understood 11 out of 12 basic science concepts in courses offered in their first and second years, with confidence in basic science topics significantly improving from the second to third year. The lack of demonstrated improvement in interdisciplinary understanding across the curriculum may be attributed to the fact that students are able to integrate basic science topics with foundational immunologic concepts as early as their second year. Importantly, these findings suggest that the integration or review of basic science topics in an immunology course may improve students' comprehension of foundational immunology concepts and interdisciplinary science competency.

Toll-like receptors (TLRs) are innate immune sensors for the presence of pathogens and endogenous danger signals. TLR activation results in conserved intracellular signaling events that orchestrate inflammation and antimicrobial defense. While the identity and interplay of key TLR signaling components are well established, how these largely cytosolic proteins are physically connected is not well understood. For the activation of conserved intracellular signaling events, most TLRs engage the adapter MyD88 (myeloid differentiation primary response 88), which assembles into higher-order protein complexes, myddosomes. In their recent publication, Fisch et al. present evidence that oligomeric myddosomes detach from initiating TLRs and evolve into larger scaffolds that dynamically assemble not only proximal but also distal cytosolic elements required to execute the entire cascade of the TLR–MyD88 signaling pathway. Coinciding with decline in TLR signaling over time, myddosomes progressively recruit autophagy machinery that mediates myddosome clearance. These findings expand the current understanding of TLR signaling by positioning myddosomes as the central structural element that physically assembles the key executors and regulators of TLR–MyD88-dependent intracellular signaling cascades.

Sharing a passion for the advancement of the discipline, the scientific community provides an authentic environment for new members to acquire the knowledge and develop the professional identity needed for their future careers. Supporting opportunities for higher education students to participate in this community can complement their classroom-based education and be extremely beneficial to their learning. Situated in the authentic environment of the scientific community, conferences are organized events where professionals meet to advance their discipline, and which have been shown to provide unique learning opportunities for university students. Here we present a modular framework created to support Imperial College London's Master of Science in Immunology students' attendance at the British Society for Immunology Annual Congress. The module's evaluation indicates an overall students' satisfaction with the content, organization, teaching, assessment, feedback and community aspects of the framework and draws attention to areas of potential improvements. Furthermore, the data emphasize the importance of preconference preparation, of academic mentoring and discusses the role of peer support. Finally, the data highlight the benefits for students of discovering the true breadth and depth of their discipline, of interacting with members of the community and how these contribute to the development of their professional identity.

A hemocytometer is a key piece of laboratory equipment typically used in diagnostic and immunology research laboratories to enumerate white blood cells. The accurate quantification of cell density is essential to ensure accurate numbers of cells are added to assays to generate valid data. Hence, learning to correctly use a hemocytometer is a critical skill for all undergraduate immunology students. However, this skill can be challenging to learn because of students' unfamiliarity with correct cell identification, differentiating viable versus dead cells and mathematical proficiency in calculating cell density and viability. To address these issues, we developed an interactive computer simulation that replicated all aspects of a Neubauer-style hemocytometer. This simulation was used to teach second-year undergraduate immunology students before a face-to-face (F-2-F) laboratory exercise where these skills were applied. Using a mixed methods approach, student performance and feedback were collected on broad aspects of the intervention and its benefits to the F-2-F setting. The approach was found to be extremely successful with all measures indicating a significant impact of the virtual hemocytometer on student learning, understanding and confidence. We suggest that integrating an online simulation to teach students the fundamentals of hemocytometer use and calculations is a valuable educational aid for learning this important skill.

Head and neck cancer (HNC) is the seventh most common cancer globally, resulting in 440 000 deaths per year. While there have been advancements in chemoradiotherapy and surgery, relapse occurs in more than half of HNCs, and these patients have a median survival of 10 months and a 2-year survival of < 20%. Only a subset of patients displays durable benefits from immunotherapies in metastatic and recurrent HNC, making it critical to understand the tumor microenvironment (TME) underpinning therapy responses in HNC. To recognize biological differences within the TME that may be predictive of immunotherapy response, we applied cutting-edge geospatial whole-transcriptome profiling (NanoString GeoMx Digital Spatial Profiler) and spatial proteomics profiling (Akoya PhenoCycler-Fusion) on a tumor microarray consisting of 25 cores from 12 patients that included 4 immunotherapy-unresponsive (8 cores) and 2 immunotherapy-responsive patients (5 cores), as well as 6 immunotherapy naïve patients (12 cores). Through high-plex, regional-based transcriptomic mapping of the tumor and TME, pathways involved with the complement system and hypoxia were identified to be differentially expressed in patients who went on to experience a poor immunotherapy response. Single-cell, targeted proteomic analysis found that immune cell infiltration of the cancer cell mass and interactions of CD8 T cells with tumor and other immune cells were associated with positive immunotherapy response. The relative abundance of specific tumor phenotypes and their interactions with various immune cells was identified to be different between response groups. This study demonstrates how spatial transcriptomics and proteomics can resolve novel alterations in the TME of HNC that may contribute to therapy sensitivity and resistance.