Immune Cell Dynamics Research Articles

The Influence of Circulating Immune Cell and CA125 Dynamics on Neoadjuvant Therapy Selection for Advanced Ovarian Cancer.

Background and Objectives: Ovarian cancer, including tubal and peritoneal cancer, is the third most common gynecological cancer and the leading cause of death from gynecological malignancies in developed countries. This study explores the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in determining the optimal duration of neoadjuvant chemotherapy (NACT) for advanced ovarian cancer. It also investigates the correlation between NLR dynamics and the KELIM score, a chemosensitivity marker, to enhance individualized therapeutic strategies. Materials and Methods: A total of 79 patients underwent NACT followed by interval debulking surgery (IDS) or palliative care. The data collected included demographic information, tumor characteristics, treatment modalities, and laboratory parameters. The baseline NLR (NLR-T0) and post-therapeutic NLR (NLR-T1) were calculated, and their variation (NLR∆) was analyzed. The KELIM score was determined using CA-125 values. Results: Patients with a high baseline NLR (≥2.5) had significantly worse progression-free survival (PFS) and overall survival (OS) compared to those with a low NLR (<2.5). A negative NLR∆ was associated with poorer PFS and OS. The KELIM score indicated a more effective treatment response, with higher scores correlating with better outcomes. The majority of patients achieved R0 resection, and those with favorable KELIM scores showed improved survival rates. Conclusions: The NLR is a valuable prognostic marker for assessing treatment response and guiding NACT duration in advanced ovarian cancer.

Time - The fourth dimension of immune cells.

Deciphering the intricate cell-state transitions orchestrating immune adaptation over time stands as a cornerstone for advancing biological understanding. However, the lack of empirical in vivo genomic technologies capable of capturing cellular dynamics has posed a significant challenge. In response to this gap, a groundbreaking study introduces Zman-seq, a single-cell technology that records transcriptomic dynamics across time by incorporating time stamps into circulating immune cells, enabling their tracking in tissues for extended periods. The application of Zman-seq in glioblastoma research has successfully unraveled the cell state and molecular trajectories underlying the dysfunctional immune microenvironment. Understanding the temporal aspects of cell-state transitions during immune responses is pivotal for advancing our knowledge in biology. The emergence of Zman-seq addresses the current limitations in empirical in vivo genomic technologies, offering a revolutionary approach to studying the dynamics of immune cells over time. This highlight comprehensively explores the implications of Zman-seq in resolving cell-state transitions and molecular trajectories within the dysfunctional immune microenvironment in different types of immunotherapy. This technique has particular potential for chimeric antigen receptor T-cell therapy, overriding drug resistance, clinical medication optimization, and facilitating drug development. In particular, this article discusses potential strategies for improving the efficacy of clinical treatments.

Modeling the Immune System Through Agent-based Modeling: A Mini-review

The immune system plays a critical role in protecting the human body against various pathogens and diseases. Understanding the complexity and dynamics of the immune system is essential for developing effective therapies and interventions. Agent-based modeling (ABM) has emerged as a powerful tool for simulating and studying the behavior of complex systems, including the immune system. This review examines the advantages, challenges, and applications of ABM in immune system modeling. ABM captures the complexity of immune cell behavior, spatial effects and stochasticity. It has been applied to study immune cell dynamics, immune responses to pathogens, immune cell migration, immunotherapies and immune system disorders. Challenges include parameterization, validation, and computational resource requirements. Future directions involve integrating multi-omics and single-cell data, incorporating machine learning, exploring multi-scale modeling, and developing user-friendly interfaces. ABM holds promise for enhancing our understanding of immune system dynamics and advancing diagnostics and treatments in immunology.

The axillary lymphoid organ - an external, experimentally accessible immune organ in the zebrafish.

Lymph nodes and other secondary lymphoid organs play critical roles in immune surveillance and immune activation in mammals, but the deep internal locations of these organs make it challenging to image and study them in living animals. Here, we describe a previously uncharacterized external immune organ in the zebrafish ideally suited for studying immune cell dynamics in vivo, the axillary lymphoid organ (ALO). This small, translucent organ has an outer cortex teeming with immune cells, an inner medulla with a mesh-like network of fibroblastic reticular cells along which immune cells migrate, and a network of lymphatic vessels draining to a large adjacent lymph sac. Noninvasive high-resolution imaging of transgenically marked immune cells can be carried out in the lobes of living animals, and the ALO is readily accessible to external treatment. This newly discovered tissue provides a superb model for dynamic live imaging of immune cells and their interaction with pathogens and surrounding tissues, including blood and lymphatic vessels.

Mitigating Viral Impact on the Radiation Response of the Lung.

Inflammation is a key factor in both influenza and radiation-induced lung pathophysiology. This implies a commonality of response to pulmonary damage from these insults and suggests exacerbated pathology may occur after combined exposure. We therefore tested the hypothesis that past inflammation from viral infection alters the lung microenvironment and lowers tolerance for radiation injury. Mice were inoculated with influenza A virus (IAV) and three weeks later, after virus clearance, mice received total-body irradiation (TBI). Survival as well as systemic and local lung inflammation were assessed, and strategies to mitigate pulmonary injury were investigated. After IAV infection alone, body condition recovered within 3 weeks, however inflammatory pathways remained active for 15 weeks. IAV infection exacerbated subsequent TBI responses, evident by increased lethality, enhanced histologically evident lung injury and an altered lung macrophage phenotype. To mitigate this enhanced sensitivity, captopril [an angiotensin converting enzyme inhibitor (ACEi)] was administered to limit tissue inflammation, or inflammatory monocyte-derived macrophage recruitment was blocked with a C-C chemokine receptor type 2 (CCR2) inhibitor. Both treatments abrogated the changes in circulating immune cells observed 4 weeks after TBI, and attenuated pro-inflammatory phenotypes in lung alveolar macrophages, appearing to shift immune cell dynamics towards recovery. Histologically apparent lung injury was not improved by either treatment. We show that latent lung injury from viral infection exacerbates radiation morbidity and mortality. Although strategies that attenuate proinflammatory immune cell phenotypes can normalize macrophage dynamics, this does not fully mitigate lung injury. Recognizing that past viral infections can enhance lung radiosensitivity is of critical importance for patients receiving TBI, as it could increase the incidence of adverse outcomes.

Single-cell transcriptomic analysis of immune cell dynamics in the healthy human endometrium

The microenvironment of the endometrial immune system is crucial to the success of placental implantation and healthy pregnancy. However, the functionalities of immune cells across various stages of the reproductive cycle have yet to be fully comprehended. To address this, we conducted advanced bioinformatic analysis on 230,049 high-quality single-cell transcriptomes from healthy endometrial samples obtained during the proliferative, secretory, early pregnancy, and late pregnancy stages. Our investigation has unveiled that proliferative natural killer (NK) cells, a potential source of endometrial NK cells, exhibit the most robust proliferative and differentiation potential during non-pregnant stages. We have also identified similar differentiation trajectories of NK cells originating from proliferative NK cells across four stages. Notably, during early pregnancy, NK cells demonstrate the highest oxidative phosphorylation metabolism activity, and, in conjunction with macrophages and T cells, exhibit the strongest type II interferon response. With spatial transcriptome data, we have discerned that the most robust immune-non-immune interactions are associated with the promotion and inhibition of cell proliferation, differentiation and migration during four stages. Furthermore, we have compiled lists of stage-specific risk genes implicated in reproductive diseases, which hold promise as potential disease biomarkers. Our study provides insights into the dynamics of the endometrial immune microenvironment during different reproductive cycle stages, thus serving as a reference for detecting pathological changes during pregnancy.

Monitoring Circulating Myeloid Cells in Peritonitis with an In Vivo Imaging Flow Cytometer.

Peritonitis is a common and life-threatening inflammatory disease. Myeloid cells are elevated in the peripheral blood and contribute to peritonitis, but their circulating dynamics are not clear. In vivo flow cytometry (IVFC) is a noninvasive technique for monitoring the dynamics of circulating cells in live animals. It has been extensively used to detect circulating tumor cells, but rarely for monitoring immune cells. Here, we describe a method adapting an intravital microscope for IVFC so that we can monitor LysM-EGFP-labeled circulating myeloid cells in a tumor necrosis factor (TNF) α-induced peritonitis mouse model. Using this IVFC method, we quantified the blood flow velocity and cell concentration in circulation. We observed a significant increase in LysM-EGFP+ cells in circulation after TNFα intraperitoneal (i.p.) injection, which reached a plateau in ~20 min. Conventional cytometry analysis showed that most LysM-EGFP+ cells were neutrophils. Increasing blood neutrophils were accompanied by neutrophil recruitment to the peritoneal cavity and neutrophil emigration from the bone marrow. We then monitored neutrophil CD64 expression in vivo and found a significant increase in TNFα-induced peritonitis. We also found that CD18 blockade doubled the circulating neutrophil number in TNFα-induced peritonitis, suggesting that CD18 is critical for neutrophil recruitment in peritonitis. Overall, we demonstrate that IVFC techniques are useful for studying the circulating dynamics of immune cells during inflammatory diseases.

Immune disease dialogue of chemokine-based cell communications as revealed by single-cell RNA sequencing meta-analysis.

Immune-mediated diseases are characterized by aberrant immune responses, posing significant challenges to global health. In both inflammatory and autoimmune diseases, dysregulated immune reactions mediated by tissue-residing immune and non-immune cells precipitate chronic inflammation and tissue damage that is amplified by peripheral immune cell extravasation into the tissue. Chemokine receptors are pivotal in orchestrating immune cell migration, yet deciphering the signaling code across cell types, diseases and tissues remains an open challenge. To delineate disease-specific cell-cell communications involved in immune cell migration, we conducted a meta-analysis of publicly available single-cell RNA sequencing (scRNA-seq) data across diverse immune diseases and tissues. Our comprehensive analysis spanned multiple immune disorders affecting major organs: atopic dermatitis and psoriasis (skin), chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis (lung), ulcerative colitis (colon), IgA nephropathy and lupus nephritis (kidney). By interrogating ligand-receptor (L-R) interactions, alterations in cell proportions, and differential gene expression, we unveiled intricate disease-specific and common immune cell chemoattraction and extravasation patterns. Our findings delineate disease-specific L-R networks and shed light on shared immune responses across tissues and diseases. Insights gleaned from this analysis hold promise for the development of targeted therapeutics aimed at modulating immune cell migration to mitigate inflammation and tissue damage. This nuanced understanding of immune cell dynamics at the single-cell resolution opens avenues for precision medicine in immune disease management.

Immune Cell Dynamics in EGFR-Mutated NSCLC Treated With Afatinib and Pembrolizumab: Results From a Phase IB Study

IntroductionEGFR-mutated NSCLC is minimally responsive to programmed cell death protein 1 or programmed death-ligand 1 blockade. We evaluated the safety, tolerability, and immunomodulatory effects of the EGFR tyrosine kinase inhibitor (TKI) afatinib in combination with the programmed cell death protein 1 antibody pembrolizumab in patients with EGFR-mutant NSCLC. MethodsPatients with advanced EGFR-mutant NSCLC with progression (PD) on previous EGFR TKI(s), aged above or equal to 18 years, Eastern Cooperative Oncology Group performance status less than or equal to 1, acceptable organ function, no significant autoimmune disease, measurable disease, and controlled brain metastases were eligible. Primary end point was determination of the maximum tolerated dose and recommended phase 2 dose. Serial specimens were collected to assess for alterations in cytokines and immune cell subsets by quantitative immunofluorescence in tissue and Luminex and flow cytometry in the blood. ResultsA total of 11 patients were enrolled, six in dose finding and five in dose expansion. No dose-limiting toxicities were observed. The maximum tolerated dose was determined to be afatinib 40 mg orally daily and pembrolizumab 200 mg intravenously every 21 days. Four (36%) patients had immune-related adverse events (irAEs). Ten patients were assessable for response: two partial response, seven stable disease, and one PD. Peripheral natural killer and natural killer T-cells (p = 0.027, p = 0.01) increased and exhausted CD8+ T-cells decreased on treatment (p = 0.0035). Peripheral CD4/CD8 T-cells (area under the curve = 0.96, p = 0.042) and central memory T-cells (CD4/CD8) (area under the curve = 1.0, p = 0.0006) increased in patients who had disease control more than 6 months or partial response to afatinib/pembrolizumab as did CD3+ T-cells in a patient with progression-free survival more than 6 months after afatinib/pembrolizumab treatment. ConclusionsAfatinib and pembrolizumab were found to have modest activity associated with irAEs after PD on previous EGFR TKI setting. Proinflammatory changes in immune cell subsets in tissue and blood were detected and associated with antitumor activity and irAEs.

Dendritic cells steering antigen and leukocyte traffic in lymph nodes.

Dendritic cells (DCs) play a central role in initiating and shaping the adaptive immune response, thanks to their ability to uptake antigens and present them to Tcells. Once in the lymph node (LN), DCs can spread the antigen to other DCs, expanding the pool of cells capable of activating specific T-cell clones. Additionally, DCs can modulate the dynamics of other immune cells, by increasing naïve T-cell dwell time, thereby facilitating the scanning for cognate antigens, and by selectively recruiting other leukocytes. Here we discuss the role of DCs in orchestrating antigen and leukocyte trafficking within the LN, together with the implications of this trafficking on T-cell activation and commitment to effector function.

Unraveling dynamic immunological landscapes in intracerebral hemorrhage: insights from single-cell and spatial transcriptomic profiling.

Intracerebral hemorrhage (ICH) poses a formidable challenge in stroke management, with limited therapeutic options, particularly in the realm of immune-targeted interventions. Clinical trials targeting immune responses post-ICH have encountered setbacks, potentially attributable to the substantial cellular heterogeneity and intricate intercellular networks within the brain. Here, we present a pioneering investigation utilizing single-cell RNA sequencing and spatial transcriptome profiling at hyperacute (1h), acute (24h), and subacute (7 days) intervals post-ICH, aimed at unraveling the dynamic immunological landscape and spatial distributions within the cerebral tissue. Our comprehensive analysis revealed distinct cell differentiation patterns among myeloid and lymphocyte populations, along with delineated spatial distributions across various brain regions. Notably, we identified a subset of lymphocytes characterized by the expression of Spp1 and Lyz2, termed macrophage-associated lymphocytes, which exhibited close interactions with myeloid cells. Specifically, we observed prominent interactions between Lgmn+Macro-T cells and microglia through the spp1-cd44 pathway during the acute phase post-ICH in the choroid plexus. These findings represent a significant advancement in our understanding of immune cell dynamics at single-cell resolution across distinct post-ICH time points, thereby laying the groundwork for exploring critical temporal windows and informing the development of targeted therapeutic strategies.

Comprehensive immune modulation mechanisms of Angong Niuhuang Wan in ischemic stroke: Insights from mass cytometry analysis.

Angong Niuhuang Wan (AGNHW, ), is a classical medicinal formula in Traditional Chinese Medicine (TCM) that has been appreciated for its neuroprotective properties in ischemic cerebral injuries, yet its intricate mechanisms remain only partially elucidated. This study leverages advanced Mass cytometry (CyTOF) to analyze AGNHW's multifaceted immunomodulation effects in-depth, emphasizing previously underexplored areas. AGNHW mitigated monocyte-derived macrophages (MoDM) infiltration in the brain, distinguishing its effects on those from microglia. While the vehicle group exhibited elevated inflammatory markers like CD4, CD8a, and CD44 in ischemic brains, the AGNHW-treated group attenuated their expressions, indicating AGNHW's potential to temper the post-ischemic inflammatory response. Systemically, AGNHW modulated fundamental immune cell dynamics, notably augmenting CD8+ T cells, B cells, monocytes, and neutrophil counts in the peripheral blood under post-stroke conditions. Intracellularly, AGNHW exhibited its targeted modulation of the signaling pathways, revealing a remarked inhibition of key markers like IκBα, indicating potential suppression of inflammatory responses in ischemic brain injuries. This study offers a comprehensive portrait of AGNHW's immunomodulation effects on ischemic stroke, illuminating its dual sites of action-both cerebral and systemic-and its nuanced modulation of cellular and molecular dynamics.

Temporal-specific single-cell atlas of human type A aortic dissection reveals immune cell dynamics and therapeutic targets

Temporal-specific single-cell atlas of human type A aortic dissection reveals immune cell dynamics and therapeutic targets

Deciphering COPS5 influence on immune infiltration and prognosis in head and neck squamous cell carcinoma

Head and Neck Squamous Cell Carcinoma (HNSCC) is a widespread malignancy originating from the mucous epithelium of the oral cavity, pharynx, and larynx. Despite advances in diagnostic and therapeutic modalities, the prognosis of HNSCC remains challenging. This study investigates the intricate relationship among COPS5, immune infiltration patterns, and prognostic implications in HNSCC. Through comprehensive analyses of 519 HNSCC cases from TCGA and single-cell data from the GEO database, we utilize the CIBERSORT algorithm to discern immune cell dynamics influenced by COPS5 expression. Notably, Treg cells emerge as a central point in the interplay between COPS5 and immune modulation. Further analyses, encompassing differential gene expression, immune-related gene set enrichment, and protein-protein interaction networks, elucidate the molecular landscape associated with COPS5 in HNSCC. A prognostic risk model, incorporating CD27, TNFRSF4, FADD, and PSMD14, is formulated and validated across diverse datasets. The model demonstrates robust predictive power, underscoring its potential as a valuable prognostic tool. These genes, essential for immune regulation and cell cycle control, provide insights into the intricate mechanisms influencing HNSCC progression. In conclusion, this study not only reveals the impact of COPS5 on immune dynamics in HNSCC but also introduces a concise and effective prognostic model.

CD5L is upregulated upon infection with Mycobacterium tuberculosis with no effect on disease progression.

Tuberculosis (TB) alone caused over a billion deaths in the last 200 years, making it one of the deadliest diseases to humankind. Understanding the immune mechanisms underlying protection or pathology in TB is key to uncover the much needed innovative approaches to tackle TB. The scavenger receptor cysteine-rich molecule CD5 antigen-like (CD5L) has been associated with TB, but whether and how CD5L shapes the immune response during the course of disease remains poorly understood. Here, we show an upregulation of CD5L in circulation and at the site of infection in C57BL/6 Mycobacterium tuberculosis-infected mice. To investigate the role of CD5L in TB, we studied the progression of M. tuberculosis aerosol infection in a recently described genetically engineered mouse model lacking CD5L. Despite the increase of CD5L during infection of wild-type mice, absence of CD5L did not impact bacterial burden, histopathology or survival of infected mice. Absence of CD5L associated with a modest increase in the numbers of CD4+ T cells and the expression of IFN-γ in the lungs of infected mice, with no major effect in overall immune cell dynamics. Collectively, this study confirms CD5L as a potential diagnostic biomarker to TB, showing no discernible impact on the outcome of the infection.

CD8+ T cells promote ZIKV clearance and mitigate testicular damage in mice

Zika virus (ZIKV) causes human testicular inflammation and alterations in sperm parameters and causes testicular damage in mouse models. The involvement of individual immune cells in testicular damage is not fully understood. We detected virus in the testes of the interferon (IFN) α/β receptor−/− A129 mice three weeks post-infection and found elevated chemokines in the testes, suggesting chronic inflammation and long-term infection play a role in testicular damage. In the testes, myeloid cells and CD4+ T cells were absent at 7 dpi but were present at 23 days post-infection (dpi), and CD8+ T cell infiltration started at 7 dpi. CD8−/− mice with an antibody-depleted IFN response had a significant reduction in spermatogenesis, indicating that CD8+ T cells are essential to prevent testicular damage during long-term ZIKV infections. Our findings on the dynamics of testicular immune cells and the importance of CD8+ T cells function as a framework to understand mechanisms underlying observed inflammation and sperm alterations in humans.

Insights into beige phenotype and immune cell dynamics of human epicardial adipose tissue.

Insights into beige phenotype and immune cell dynamics of human epicardial adipose tissue.

Fast but not furious: neonatal cardiac fibroblasts as promoters of regeneration after myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): Fundação para a Ciência e Tecnologia (FCT) Introduction Mouse neonates at postnatal day 1 (P1) regenerate their hearts after myocardial infarction (MI) but this capacity is transient. Seven day-old animals (P7) develop a reparative response similar to adults, with ischemic tissue being progressively replaced by a rigid fibrotic scar mainly produced by activated cardiac fibroblasts (CF). Recent works support that CF are likely to play an important role in mediating the regeneration-to-repair transition, but the current knowledge is limited. Aims Our final goal is to unravel CF-mediated mechanisms that confer regenerative potential to the neonatal heart and later reactivate these processes in the context of adult MI. Methods Ventricles from non-manipulated mice at different developmental stages were subjected to targeted RNA-seq. CF were isolated by FACS from P1 (regenerative) and P7 (reparative) hearts and characterized at the transcriptional, phenotypic and functional level in vitro. MI was induced by permanent ligation of the left anterior descending coronary artery at P1 and P7. CF and immune cell dynamics were assessed at different timepoints after MI by flow cytometry and immunofluorescence (IF). Transcriptomics of FACS-sorted CF from sham-operated and infarcted hearts at P1 and P7 were assessed by targeted RNA-seq. Intramyocardial injections of either P1 or P7 CF in MI-operated P1 hearts were performed immediately after surgery and hearts were analysed by IF at 7 and 14 days after injury. Results Severe transcriptional alterations on extracellular matrix (ECM) genes were found between P1 (regenerative) and P7 (reparative) hearts. Concomitantly, CF were shown to progressively infiltrate the myocardium and undergo a phenotypic shift that recapitulates transcriptional alterations observed for ECM-encoding genes in the heart. In vitro, CF at P7 show increased proliferation, migration capacity and TGF-β responsiveness. After MI at P1, CF participate in the regenerative response through a fast and transient recruitment to the ischemic site, returning to basal levels at day 7, a period in which CM proliferation and neovascularization are upregulated. Contrarily, MI at P7 resulted in permanent loss of CM, impaired neovascularization and formation of aberrant fibrosis as a result of exuberant and persistent CF recruitment and activation. Whole transcriptomic analysis further showed CF from MI at P7 are highly reactive to injury and engage on the expression of ECM components. The injection of CF resulted in a reduced heart weight and accumulation of cells in the injury site at 7 and 14 days after MI, which suggests a delay in regeneration. Conclusion Physiological CF development after birth entails a shift from a pro-regenerative to a pro-fibrotic phenotype that impacts on the regenerative capacity of the heart and determines the persistent CF activation and permanent scarring after P7.

Plasma immune signatures can predict rejection-free survival in the first year after pediatric liver transplantation

After pediatric liver transplantation (pLT), children undergo life-long immunosuppression since reliable biomarkers for the assessment of rejection probability are scarce. In the multicenter (n= 7) prospective clinical cohort "ChilSFree" study, we aimed to characterize longitudinal dynamics of soluble and cellular immune mediators during the first year after pLT and identify early biomarkers associated with outcome. Using a Luminex-based multiplex technique paired with flow cytometry, we characterized longitudinal dynamics of soluble immune mediators (SIMs, n= 50) and immune cells in the blood of 244 patients at eight visits over 1 year: before, and 7/14/21/28 days and 3/6/12 months after pLT. The unsupervised clustering of patients based on SIM profiles revealed six unique SIM signatures associated with clinical outcome. From three signatures linked to improved outcome, one was associated with 1-year-long rejection-free survival and stable graft function and was characterized by low levels of pro-inflammatory SIMs (CXCL8/9/10/12, CCL7, SCGF-β, sICAM-1), and high levels of regenerative (SCF, TNF-β) and pro-apoptotic (TRAIL) SIMs (all, p <0.001, fold change >100). Of note, this SIM signature appeared 2 weeks after pLT and remained stable over the entire year, pointing towards its potential as a novel early biomarker for minimizing or weaning immunosuppression. In the blood of these patients, a higher frequency of CD56bright natural killer cells (p <0.01), a known hallmark also associated with operationally tolerant pLT patients, was detected. The concordance of the model for prediction of rejection based on identified SIM signatures was 0.715, and 0.795, in combination with living-related transplantation as a covariate, respectively. SIM blood signatures may enable the non-invasive and early assessment of rejection risks in the first year after pLT, paving the way for improved clinical management. ChilSFree represents the largest pediatric liver transplant (pLT) cohort with paired longitudinal data on soluble immune mediators (SIMs) and immune phenotyping in the first year after pLT. SIM signatures allow for the selection of rejection-free patients 2 weeks after pLT independently of patient diagnosis, sex, or age. The SIM signatures may enable the non-invasive and early assessment of rejection risks, paving the way for minimization or withdrawal of immunosuppression after pLT.

EMP1 correlated with cancer progression and immune characteristics in pan-cancer and ovarian cancer.

This study examines the prognostic role and immunological relevance of EMP1 (epithelial membrane protein-1) in a pan-cancer analysis, with a focus on ovarian cancer. Utilizing data from TCGA, CCLE, and GTEx databases, we assessed EMP1 mRNA expression and its correlation with tumor progression, prognosis, and immune microenvironment across various cancers. Our results indicate that EMP1 expression is significantly associated with poor prognosis in multiple cancer types, including ovarian, bladder, testicular, pancreatic, breast, brain, and uveal melanoma. Immune-related analyses reveal a positive correlation between EMP1 and immune cell infiltration, particularly neutrophils, macrophages, and dendritic cells, as well as high expression of immune checkpoint such as CD274, HAVCR2, IL10, PDCD1LG2, and TGFB1 in most tumors. In vivo experiments confirm that EMP1 promotes ovarian cancer cell proliferation, metastasis, and invasion. In conclusion, EMP1 emerges as a potential prognostic biomarker and therapeutic target in various cancers, particularly ovarian cancer, due to its influence on tumor progression and immune cell dynamics. Further research is warranted to elucidate the precise mechanisms of EMP1 in cancer biology and to translate these findings into clinical applications.