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PubMed2026

Analysis of end-stage renal disease mediated by cuproptosis-related genes.

OBJECTIVE: The complex pathophysiological mechanism of end-stage renal disease (ESRD) has not been fully understood. Cuproptosis is a newly discovered type of programmed cell death. Therefore, this study attempts to clarify the relationship between cuproptosis-related genes (CRGs) and the phenotype of ESRD. MATERIALS AND METHODS: The National Center for Biological Information Gene Expression Omnibus database was applied to obtain the GSE37171 dataset comprising whole-genome microarray analysis of peripheral blood samples. A 3 : 1 case-control design was employed with 75 ESRD patients and 20 healthy controls who were frequency-matched for age, sex, and ethnicity. Based on differentially expressed genes (DEGs) and genes related to cuproptosis, CRGs were identified. Thereafter, we explored two different subpopulations based on the cuproptosis gene and analyzed their expression and immune infiltration. Genes specific to the CRG cluster were identified through the weighted gene co-expression network analysis algorithm, and the best prediction model was determined and verified by four machine learning methods. RESULTS: The study identified 14 differentially expressed CRGs, among which ATP7B, SLC31A1, LIAS, LIPT1, DLD, MTF1, CDKN2A, DBT, and DLST had relatively high expression levels in the ESRD samples. Compared with the control group, expression levels of FDX1, DLAT, PDHA1, PDHB, and GLS were significantly lower in the ESRD group, and CRGs played a key role in the regulation of immune infiltration in ESRD. Two cuproptosis-related molecular clusters were identified in the ESRD samples. Cluster2 was more correlated with the immune infiltration of ESRD. By analyzing the intersection points between CRG cluster and key genes of ESRD, a total of 888 specific DEGs were identified. Functional differences related to specific DEGs were further explored using gene set variation analysis. Five significant genes (SMC5, USP47, USP53, AGA, and DMXL1) were identified by the support vector machine model as key predictors for ESRD disease risk, achieving an area under the curve (AUC) of 1.00 in internal validation. However, external validation in independent cohorts is required prior to clinical application. Individual gene analysis showed an AUC > 0.81 in discriminating ESRD patients from healthy controls, and the expression of all 5 genes in ESRD patients was significantly lower than in the control group. CONCLUSION: This study clarified the relationship between CRGs and the phenotype of ESRD, analyzed their specific roles in the immune microenvironment, and obtained a predictive model, providing new insights for the study of its potential therapeutic targets.

Humans↗
PubMed2026

Integrated transcriptomic and immunogenomic analysis unravels the immunological functions and prognostic landscape of WD repeat domain 76.

BackgroundWD Repeat Domain 76 (WDR76) plays a potential role in cellular regulation; however, its comprehensive landscape across human malignancies and its specific biological function in hepatocellular carcinoma (HCC) remain largely unexplored.MethodsWe conducted a systematic pan-cancer analysis utilizing multi-omics data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) atabases to evaluate WDR76 expression, subcellular localization, and its correlation with clinicopathologic features, genomic instability, and immune infiltration. Diagnostic and prognostic values were assessed via Receiver operating characteristic (ROC) and Kaplan-Meier analyses. Furthermore, the functional role of WDR76 in HCC was validated in vitro using Hep-3B and Huh7 cell lines through siRNA-mediated knockdown, followed by CCK-8, wound-healing, and transwell assays.ResultsWDR76 was significantly upregulated in the majority of tumor types, including LIHC, LUAD, and COAD, while exhibiting nuclear localization. Elevated WDR76 expression correlated with advanced tumor staging, metastasis, and poor clinical outcomes across multiple cohorts, particularly in ACC, KIRP, and LIHC. ROC analysis highlighted its exceptional diagnostic precision in cancers such as GBM and LIHC. Immunologically, WDR76 expression was intricately linked to immune cell infiltration, immune checkpoint markers, and genomic instability parameters, suggesting a role in shaping the tumor microenvironment. Drug sensitivity profiling revealed that high WDR76 levels correlate with resistance to specific chemotherapeutic agents. Experimentally, silencing WDR76 in HCC cells significantly suppressed cell proliferation, migration, and invasion capabilities.ConclusionOur study establishes WDR76 as a robust pan-cancer prognostic biomarker and a potential immunotherapeutic target. Specifically, we provide experimental evidence that WDR76 functions as an oncogenic driver in liver cancer, promoting malignant phenotypes and offering a novel avenue for targeted therapeutic intervention.

Humans↗
PubMed2006

Monocyte/macrophage infiltration in tumors: modulators of angiogenesis.

The role of a tumor immune infiltrate in cancer progression and metastasis has been debated frequently. Although often considered to be associated with improved prognosis and leading to the enhanced survival of cancer patients, inflammatory cells have also been described to assist the tumor's capabilities to progress, proliferate, and metastasize. Tumor-associated macrophages (TAMs), for example, have been shown to be symbiotically related to tumor cells: Tumor cells recruit TAMs and provide them with survival factors, and TAMs in turn produce a variety of angiogenic factors in response to the tumor microenvironment. This review will describe the composition of an immune infiltrate in tumors and the angiogenic and angiostatic properties of the cells present. Special emphasis will be on the angiogenesis-associated activities of TAMs. The development of immunotherapy and gene therapy using TAMs to mediate tumor cytotoxicity or to deliver gene constructs will be discussed as well. As immunotherapy has so far not been as effective as anticipated, a combination therapy in which angiostatic agents are used as well is put forward as a novel strategy to treat cancer.

Angiogenesis Inhibitors↗
PubMed2026

Transcriptome Analysis, Machine Learning, and Experimental Identification of CDK7 Affecting the Progression of Pregnancy-induced Hypertension by Influencing Macrophage Polarization.

INTRODUCTION: Pregnancy-induced hypertension (PIH) is a severe pregnancy complication characterized by placental insufficiency, abnormal vascular remodeling, and immune dysregulation, but personalized therapeutic markers remain unclear. This study aimed to identify key genes and explore immune mechanisms in PIH using transcriptome analysis, machine learning, and experimental validation. METHODS: We analyzed the GSE204835 transcriptomic dataset to screen differentially expressed genes (DEGs) and performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and Gene Set Enrichment Analysis (GSEA) for functional annotation. Immune infiltration analysis was also performed to examine the immune landscape in PIH. Least Absolute Shrinkage and Selection Operator (LASSO) regression identified key genes, which were validated in a PIH cell model. Flow cytometry and immunofluorescence assays assessed the effect of CDK7 knockdown on macrophage polarization. RESULTS: A total of 1,598 DEGs (1,123 upregulated, 475 downregulated) were identified. Enrichment analyses highlighted associations with embryonic organ development, oxidative phosphorylation, angiogenesis, and oxidative stress. Immune infiltration analysis revealed altered eosinophil and macrophage polarization in PIH. LASSO regression selected 12 key genes, with CDK7 showing the most significant upregulation in the PIH model. CDK7 knockdown promoted macrophage polarization toward the anti-inflammatory M2 phenotype. DISCUSSION: These findings link CDK7 to immune dysregulation in PIH by modulating macrophage polarization, expanding our understanding of PIH's molecular mechanisms. The study's limitations include reliance on public datasets and in vitro models, warranting in vivo validation. CONCLUSION: CDK7 emerges as a potential therapeutic target for PIH, offering new insights into immunoregulatory interventions for this complication.

Female↗
PubMed2026

Sodium Overload-Related Molecular Subtypes and a Four-Gene Prognostic Signature Predict Survival, Immune Landscape, and Therapeutic Response in Acute Myeloid Leukemia.

Sodium overload has recently emerged as a critical metabolic stressor involved in cancer progression; however, its molecular characteristics and clinical relevance in acute myeloid leukemia (AML) remain unexplored. RNA-seq data sets, clinical annotations, and mutational profiles of AML patients were annotations from The Cancer Genome Atlas and integrated with Genotype-Tissue Expression normal samples. Sodium overload-related genes (SORGs) were obtained from GeneCards. Differentially expressed SORGs (DESORGs) screened by applying the limma statistical model, followed by univariate Cox proportional hazards regression, consensus clustering, functional enrichment, immune infiltration analysis, and pathway evaluation. A prognostic signature was developed through least absolute shrinkage and selection operator regression followed by multivariate Cox modeling. The model's performance was further verified in two external GEO data sets (GSE71014 and GSE37642). Nomogram construction, subgroup analysis, tumor mutational burden (TMB) assessment, drug sensitivity prediction, transcription factor (TF) analysis, and competing endogenous RNA (ceRNA) network analyses were also performed. A total of 57 DESORGs were identified, and 2 sodium overload-related molecular subtypes exhibited distinct survival, immune infiltration, and inflammatory pathway activation. A robust four-gene signature (DOCK1, GABRE, HTR7, ACSM1) stratified patients into high- and low-risk categories with significantly different survival across training and validation cohorts. High-risk patients displayed increased immune infiltration, higher TMB, reduced sensitivity to multiple chemotherapeutic drugs, and inferior predicted response to PD-L1 blockade. TF and ceRNA networks revealed multilayered transcriptional and post-transcriptional regulation of the signature genes. This study identifies sodium overload-related molecular heterogeneity in AML and establishes a validated four-gene prognostic signature that integrates genomic, immunologic, and therapeutic features, offering potential utility for personalized risk assessment and treatment optimization.

Humans↗
PubMedDate not supplied

[Effects of triamcinolone acetonide on leukocyte distribution in blood system, mononuclear liver infiltration, and immune response under conditions of stress-induced hypoxia in rats].

The effect of triamcinolone acetonide (2 mg/kg) on the distribution of morphologically mature leukocytes in the blood system, the mononuclear liver infiltration, and the immune response was studied in rats under conditions of stress-induced hypoxia. Administered under these conditions, the drug produces a less pronounced effect on the content of circulating lymphocytes, the lymphoid cell number in the bone marrow, and the number of hepatocytes and monocytes/macrophages in the liver. However, the post-stressor immunodepressant effect of triamcinolone acetonide was increased and accompanied by the development of hepatic damage.

Animals↗
PubMed2005

[Experimental gene therapy mediated by fractalkine (FK) for murine liver cancer].

OBJECTIVES: Chemokines play an important role in the infiltration of immune cells into tumor tissues. Anti-tumor immune response has been elicited in many tumor models by chemokine gene transfection. The aim of this study was to evaluate the possibility of inducing anti-hepatocellular carcinoma active immune response by transfection of mouse hepatocellular carcinoma cells MM45T.Li with chemokine FK gene. METHODS: Mouse FK gene was transduced into mouse hepatocellular carcinoma cells MM45T.Li using of liposome.G418-resistant clones were selected and the FK mRNA expression was detected by RT-PCR. In vivo experiments were performed to observe the tumorigenicity of wild type MM45T.Li and FK gene modified tumor cells. The immune cell infiltration in tumor tissues was detected histopathologically. The level of CD4+ and CD8+ T cells in peripheral blood were detected by FACS. RESULTS: RT-PCR detection showed that FK was expressed in FK gene transfected G418-resistant clones (MM45T.Li-FK), but not in the wild type MM45T.Li. In vivo experiments the tumorigenicity of MM45T.Li-FK had decreased compared to the wild type MM45T.Li. In the tumor tissues from MM45T.Li-FK, many infiltrated immune cells were found, but few immune cells infiltrated into the tumor tissues from the controls. The level of CD4+ and CD8+ T cells had obviously increased in MM45T.Li-FK compared to the controls (P < 0.01). CONCLUSION: Transfection with chemokine FK gene can induce anti-hepatocellular carcinoma active immune response.

Animals↗
PubMed2002

Immunohistochemical studies of caveolin-3 in germ cell tumors of the testis.

BACKGROUND/AIM: Caveolin, which is a major constructive component of the caveolar membranes, plays a key role in transcytosis of molecules into cells and regulation of several signal transductions. Caveolin has three isoforms, and recent studies suggest that in some malignant tumors an alteration of caveolin-1 expression correlates with oncogenetic changes. Caveolins have been reported to be negative regulators of inducible nitric oxide synthase (iNOS) which can provoke an antitumor response via infiltrating immune cells. The aim of this study was to examine the expressions of caveolin-1 and caveolin-3 (which is a caveolin-1 homologue localized predominantly in muscle tissue) in testicular cancer. METHODS: We evaluated the expressions of caveolin-1, caveolin-3, and iNOS in 16 seminoma and 10 non-seminoma testicular cancer specimens as well as normal testicular tissue, using a streptavidin-biotin bridge technique on cryostat sections. The expression of caveolin-3 was confirmed by slot-blot analysis. Tumor-infiltrating immune cells were also studied immunohistochemically, and the correlation between the number of immune cells and caveolin-3 concentrations was calculated. RESULTS: Immunohistochemistry revealed that caveolin-3, but not caveolin-1, was frequently expressed in seminomas (12 positive out of 16 specimens) without positive staining in their normal counterparts or in nonseminomatous germ cell tumors, except for muscle components in the teratoma. iNOS was not expressed in any tissues examined. Samples with high levels of caveolin-3 tended to have higher degrees of tumor-infiltrating immune cells, although this finding was not statistically significant. CONCLUSION: This is the first report demonstrating the involvement of caveolin-3 in germ cell tumors.

Adolescent↗
PubMed2026

Pan-cancer Bioinformatics Analysis Combined with Colon Cancer Experimental Validation: A Study on TMED3 as a Diagnostic and Prognostic Biomarker.

Transmembrane Emp24 Protein Transport Domain 3 (TMED3), a member of the p24 protein family, has been implicated in tumor proliferation, invasion, and migration. This study aimed to evaluate the expression patterns, prognostic significance, immune associations, and potential biological functions of TMED3 across multiple cancer types using pan-cancer bioinformatics analysis combined with immunohistochemical (IHC) validation in colon cancer. Multiomics datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, UALCAN, Human Protein Atlas, and cBioPortal databases were analyzed to investigate TMED3 expression and genetic alterations in pan-cancer. Immunohistochemistry was performed to evaluate TMED3 protein expression in colon cancer tissues. Kaplan-Meier survival analysis and Cox regression analysis were used to assess the prognostic value of TMED3. Spearman correlation analysis was conducted to evaluate the associations of TMED3 with tumor mutational burden, microsatellite instability (MSI), immune cell infiltration, and immune checkpoints. Gene Set Enrichment Analysis was performed to investigate potential biological pathways associated with TMED3 in colon cancer. TMED3 expression was elevated in most tumor types and was associated with unfavorable overall survival and disease-specific survival in adrenocortical carcinoma, colon adenocarcinoma, and uveal melanoma. The greatest frequency of TMED3 genetic alterations was identified in mesothelioma, with amplification representing the predominant alteration type. In addition, TMED3 expression showed significant correlations with tumor mutational burden and microsatellite instability in kidney renal clear cell carcinoma, stomach adenocarcinoma, and uterine corpus endometrial carcinoma. TMED3 expression was also associated with immune infiltration and immune checkpoint expression in several tumors. IHC analysis demonstrated increased TMED3 expression in colon cancer tissues compared with normal colon tissues and showed an association with T stage. Functional enrichment analysis identified pathways related to ribosome, antigen processing and presentation, oxidative phosphorylation, and pentose phosphate. These findings indicate that TMED3 may represent a promising biomarker for the diagnosis and prognostic evaluation of colon cancer as well as other tumor types.

Humans↗
PubMed2005

Adenosine receptor signaling in the brain immune system.

The brain immune system, which consists mainly of astrocytes, microglia and infiltrating immune cells, is quiescent normally, but it is activated in response to pathophysiological events such as ischemia, trauma, inflammation and infection. Adenosine is an endogenous purine nucleoside that is generated at sites that are subjected to these "stressful" conditions. Adenosine interacts with specific G-protein-coupled receptors on astrocytes, microglia and infiltrating immune cells to regulate the function of the immune system in the brain. Although many of the effects of adenosine on immune-competent cells in the brain protect neuronal integrity, adenosine might also aggravate neuronal injury by promoting inflammatory processes. A more complete understanding of adenosine receptor function in the brain immune system should help develop novel therapeutic ways to treat brain disorders that are associated with a dysfunctional immune response.

Animals↗
PubMed2024

Biomarkers related to m6A and succinic acid metabolism in papillary thyroid carcinoma.

BACKGROUND: Studies have shown that m6A modification is related to the occurrence and development of papillary thyroid carcinoma (PTC). The disorder of succinic acid metabolism is associated with the occurrence and development of various tumors. However, there are few studies based on m6A and succinate metabolism-related genes (SMRGs) in PTC. METHODS: The TCGA-Thyroid carcinoma (THCA), GSE33630, 1159 SMRGs, and 23 m6A regulatory factors were collected from the online databases. Subsequently, the differentially expressed genes (DEGs) were selected between PTC (Tumor) and Normal samples. The overlapping genes among the DEGs, m6A, and SMRGs were applied to screen the biomarkers. Using the 3 machine-learning algorithms, the biomarkers were determined based on the overlapping genes. Next, the biomarkers were evaluated by the ROC curve and expression analysis in TCGA-THCA and GSE33630. Then, the overall survival (OS) differences were compared between the high-and low-expression biomarkers. Finally, immune infiltration analysis, molecular regulatory network, and drug prediction were performed based on the biomarkers. RESULTS: In TCGA-THCA, there were 2800 DEGs between and Normal samples, and then 7 overlapping genes were obtained. Importantly, ADK, TNFRSF10B, CYP7B1, FGFR2, and CPQ were determined as biomarkers with excellent diagnostic efficiency (AUC&#x2009;>&#x2009;0.7). In PTC samples, ADK and TNFRSF10B were high-expressed while CYP7B1, FGFR2, and CPQ were low-expressed. Especially, the high-expression groups of ADK had a better prognosis, while the high-expression groups of CYP7B1, FGFR2, and CPQ had a worse prognosis. Afterward, immune infiltration analysis found that 16 immune cells had infiltration differences between the Tumor and Normal samples. Finally, transcription factor SP1 could regulate CYP7B1 and TNFRSF10B. Moreover, Navitoclax was a potential drug for PTC patients. CONCLUSION: Overall, we described 5 biomarkers associated with adverse prognosis of PTC, including ADK, TNFRSF10B, CYP7B1, FGFR2, and CPQ. All these biomarkers were involved in succinate metabolism and m6A modification of RNA. This set of biomarkers should be explored further for their diagnostic value in PTC. Investigations into the mechanistic role of alteration of succinate metabolism and m6A modification of RNA pathways in the pathophysiology of PTC are warranted.

Humans↗
PubMed2004

Oxidative stress, renal infiltration of immune cells, and salt-sensitive hypertension: all for one and one for all.

Recent evidence indicates that interstitial infiltration of T cells and macrophages plays a role in the pathogenesis of salt-sensitive hypertension. The present review examines this evidence and summarizes the investigations linking the renal accumulation of immune cells and oxidative stress in the development of hypertension. The mechanisms involved in the hypertensive effects of oxidant stress and tubulointerstitial inflammation, in particular intrarenal ANG II activity, are discussed, focusing on their potential for sodium retention. The possibility of autoimmune reactivity in hypertension is raised in the light of the proinflammatory and immunogenic pathways stimulated by the interrelationship between oxidant stress and inflammatory response. Finally, we present some clinical considerations derived from the recognition of this interrelationship.

Humans↗
PubMed2025

CCT8 drives colorectal cancer progression via the RPL4-MDM2-p53 axis and immune modulation.

PURPOSE: Colorectal cancer (CRC) ranks high in global mortality, emphasizing the need for effective interventions. The aim of the research is to elucidate the oncogenic role of CCT8 in CRC and its interaction with RPL4 in the RPL4-MDM2-p53 axis. METHODS: TIMER 2.0, TCGA, and GTEx databases were used to analyze CCT8 expression patterns in CRC. Immunohistochemistry was performed to examine CCT8 distribution in CRC tissues and adjacent non-tumor tissues. Functional assays, including CCK-8, transwell, wound-healing, and flow cytometry, were conducted using DLD-1 and HCT116 cell lines to assess the effects of CCT8 on cell proliferation, migration, invasion, and apoptosis. Gene set enrichment analysis, protein-protein interaction network analysis, and co-immunoprecipitation were performed to explore the interaction between CCT8 and RPL4 and their role in the RPL4-MDM2-p53 pathway. Additionally, gene set variation analysis was applied to investigate the relationship between CCT8/RPL4 expression and immune infiltration patterns in CRC. RESULTS: CCT8 was significantly upregulated in CRC and associated with tumor progression. Mechanistically, CCT8 potentially synergizes with RPL4 concluded from their positive correlation and similar immune infiltration patterns, influencing the RPL4-MDM2-p53 axis and contributing to p53 ubiquitination and degradation. CONCLUSION: These findings underscore the oncogenic significance of CCT8 in CRC and shed light on its molecular mechanisms, paving the way for potential therapeutic applications.

Humans↗
PubMed2026

LINC01871-Mediated Sensitivity to Cyclin-Dependent Kinase 4/6 Inhibitors in Human Breast Cancer.

Breast cancer remains the most frequently diagnosed malignancy in women, and resistance to cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors limits long-term treatment efficacy. This study aimed to identify long non-coding RNAs (lncRNAs) associated with predicted sensitivity to CDK4/6 inhibitors and to investigate their biological functions in breast cancer. Transcriptomic data from The Cancer Genome Atlas (TCGA) and drug sensitivity data from the Genomics of Drug Sensitivity in Cancer 2 (GDSC2) database were integrated, and drug sensitivity was predicted using the oncoPredict algorithm. Candidate lncRNAs were identified through differential expression analysis, weighted gene co-expression network analysis, prognostic analysis, and machine learning. The biological functions of LINC01871 were subsequently evaluated using in vitro and in vivo experiments. Sixty-two lncRNAs associated with predicted sensitivity to ribociclib and palbociclib were identified, and six core lncRNAs were selected. LINC01871 showed the highest discriminatory performance for predicted drug sensitivity. Overexpression of LINC01871 was associated with increased sensitivity of breast cancer cells to ribociclib and palbociclib, inhibition of cell proliferation, promotion of apoptosis, and suppression of nuclear factor kappa B (NF-&#x3ba;B) signaling. Single-cell transcriptomic analysis demonstrated high LINC01871 expression in T cells and natural killer (NK) cells, while transcriptome-based immune infiltration analyses showed that high LINC01871 expression was associated with increased immune infiltration. These findings identify LINC01871 as a candidate biomarker of sensitivity to CDK4/6 inhibitors and demonstrate its tumor-suppressive effects in breast cancer. Further clinical and mechanistic studies are required to validate its predictive value and therapeutic relevance.

Humans↗
PubMed2002

Overload proteinuria is followed by salt-sensitive hypertension caused by renal infiltration of immune cells.

Recent evidence suggests that salt-sensitive hypertension develops as a consequence of renal infiltration with immunocompetent cells. We investigated whether proteinuria, which is known to induce interstitial nephritis, causes salt-sensitive hypertension. Female Lewis rats received 2 g of BSA intraperitoneally daily for 2 wk. After protein overload (PO), 6 wk of a high-salt diet induced hypertension [systolic blood pressure (SBP) = 156 +/- 11.8 mmHg], whereas rats that remained on a normal-salt diet and control rats (without PO) on a high-salt diet were normotensive. Administration of mycophenolate mofetil (20 mg. kg(-1). day(-1)) during PO resulted in prevention of proteinuria-related interstitial nephritis, reduction of renal angiotensin II-positive cells and oxidative stress (superoxide-positive cells and renal malondialdehyde content), and resistance to the hypertensive effect of the high-salt diet (SBP = 129 +/- 12.2 mmHg). The present studies support the participation of renal inflammatory infiltrate in the pathogenesis of salt-sensitive hypertension and provide a direct link between two risk factors of progressive renal damage: proteinuria and hypertension.

Animals↗
PubMed1999

Hyperacute rejection in the guinea pig-to-rat model without formation of the membrane attack complex.

The guinea pig (GP)-to-rat transplantation model has been widely used to study hyperacute rejection (HAR) of xenografts. In this model heart graft survival beyond 8 days has never been reported. In contrast, survival times of kidney and heart grafts up to 62 days have been reported in the discordant pig-to-primate model. It is not clear why it is so much more difficult to obtain long-term graft survival in the GP-to-rat model as compared to the pig-to-primate model. We hypothesized that mechanisms other than activation of complement may be involved in the rejection of guinea pig grafts by rat recipients. Therefore, we have studied in detail the rejection of GP aortic grafts by rat recipients, either PVG/c+ (complement competent, group 1), or PVG/c- (complement C6 deficient, group 2). PVG/c- rats are not able to form the membrane attack complex (MAC) of complement. Forty-four GP-to-rat aortic transplantations were performed successfully. Recipient rats were sacrificed at various intervals after transplantation (4, 24 and 48 h, and 7 and 28 days, three to six animals per time point per group). Twenty-four hours after transplantation the number of cells in the media was significantly decreased from 11.1 +/- 0.9 cells/mm2 to 3.1 +/- 2.8 cells/mm2 in group 1, whereas the number of medial cells in group 2 remained the same. The number of medial cells was significantly decreased in both groups at 48 h post-transplantation (group 1: 1.8 +/- 2.2 cells/mm2; group 2: 5.5 +/- 3.0 cells/mm2). At that time no infiltrating cells were apparent in the grafts of either two groups. Seven days after transplantation, the number of medial cells remained low in group 1 (1.8 +/- 2.9 cells/mm2) but was increased in group 2 (10.7 +/- 2.6 cells/mm2) as a consequence of infiltrating immune cells. These infiltrating cells consisted mainly of macrophages, but also T cells and NK cells. At 28 days after transplantation the grafts in both groups were completely reorganized and no distinction could be made between media and adventitia. These results show that rejection of GP grafts by rat recipients can occur in the absence of both MAC of complement and immune competent cells. This MAC and immune cells independent type of rejection has not been described before and may explain the difficulty in obtaining long-term graft survival in the GP-to-rat xenotransplantation model.

Acute Disease↗
PubMed2004

[Function and prognostic significance of immune cells infiltrating human tumors].

The presence of a mononuclear infiltrate has prognostic importance in a variety of human cancers. The infiltration by different cell types, mainly T lymphocytes and dendritic cells has been correlated to tumor size, stage, metastatization, and patients' survival. Their pathophysiological role is influenced by the cell types, their localization (intra- or peritumoral), and by tumor characteristics or patient subgroups. The prognostic significance of the different cell populations in the individual tumor types is frequently controversial, which is due, in part, to their multiple functions; for example, tumor-associated macrophages are involved in the regulation of angiogenesis beside their immunologic functions. Moreover, the presence of immune cells in the tumor does not guarantee the development of an efficient immune reaction, consequently, the degree of infiltration does not necessarily correlate with the intensity of the immune response. Therefore, recent studies emphasize the importance of the assessment of the functional and activation state of tumor infiltrating lymphocytes. Here we summarize results on the prognostic role of infiltrating mononuclear cells in human neoplasms, and present our data on studies performed on cutaneous malignant melanoma.

B-Lymphocytes↗
PubMed2026

NPLOC4 Constructs Tumor Immunosuppressive Microenvironment in Pan-cancer and Hepatocellular Carcinoma.

INTRODUCTION: NPLOC4 (nuclear protein localization 4 homolog) is mainly involved in DNA damage, cell cycle, and ubiquitination promotion. Nonetheless, the role of NPLOC4 in the tumor immune microenvironment (TIME) and its potential as a promising tumor therapeutic target remains unclear. METHODS: Therefore, analyses of NPLOC4 mRNA and protein expression, RNA subcellular localization, and patient prognosis associated with NPLOC4 expression were conducted across multiple tumor types. Additionally, the correlations between NPLOC4 and immune cells, non-immune cells, and immune molecules within the tumor immune microenvironment (TIME) were investigated. These analyses utilized data from various public resources, including the Genotype-Tissue Expression (GTEx) project, The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), The Human Protein Atlas (HPA), Clinical Proteomic Tumor Analysis Consortium (CPTAC), TIMER2.0, KM-Plotter, The University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN), and Tumor Immune Single-cell Hub 2 (TISCH2). Subsequently, we utilized hepatocellular carcinoma (HCC) patients' cancer and adjacent tissues plus tumor cell lines to verify the differential RNA and protein expression of NPLOC4 via qRT-PCR and immunohistochemistry (IHC). Then, the relationship of NPLOC4 expression level with immune infiltration score, infiltration of effector immune cells, suppressive immune cells, and several vital immune checkpoints was analyzed in HCC immune microenvironment. Furthermore, the distribution of expression of NPLOC4 in various cells in the HCC microenvironment was determined through single-cell sequencing analysis. RESULTS: We discovered that NPLOC4 was up-regulated in a variety of tumors and was correlated with poor prognosis. NPLOC4 not only had the potential as a tumor prognostic marker and therapeutic target but also was strongly linked to immune cells, immune checkpoints, and immune-related molecules and pathways in HCC immune microenvironment. CONCLUSION: In summary, NPLOC4 may serve as a promising target for immunotherapy.

Humans↗