Multiple myeloma (MM) is a malignant disorder of plasma cells. Combinations of bortezomib (BTZ) with other therapeutic agents remain the mainstay of MM treatment. However, the rising incidence of drug resistance among patients with MM underscores an urgent need for novel therapeutic strategies. The present study identified triptonide (TN), a small‑molecule monomer extracted from the traditional Chinese herb Tripterygium wilfordii Hook. f., as a synergistic agent that enhanced the anti‑MM activity of BTZ, following a screening of 198 compounds from a ubiquitination‑focused library. TN effectively inhibited cell proliferation, induced apoptosis, and reduced cell viability in MM cells. Furthermore, the synergistic anti‑MM effect between TN and BTZ was validated across MM cell lines, primary MM cells, and xenograft mouse models of MM. Mechanistic investigations revealed that TN synergizes with BTZ by enhancing DNA damage through the suppression of TRIP13‑mediated DNA repair pathways, including non‑homologous end joining and homologous recombination. Notably, TRIP13 knockdown attenuated TN‑induced DNA damage and apoptosis, and diminished the synergistic effect of TN and BTZ on MM cells. Collectively, TN represents a novel anti‑MM agent, and the combination of TN with BTZ constitutes a promising therapeutic strategy for the treatment of MM.

BACKGROUND AND PURPOSE:Aberrant protein glycosylation contributes significantly to hepatocellular carcinoma (HCC) progression. β-1,4-Galactosyltransferase 3 (B4GALT3), an enzyme involved in glycosylation, is overexpressed in HCC and promotes tumour growth by stabilizing integrin β1 (ITGB1). This study aimed to evaluate B4GALT3 as a therapeutic target and develop a precision nanotherapeutic approach for HCC. EXPERIMENTAL APPROACH:Bioinformatics analyses using TCGA-LIHC datasets identified B4GALT3 as a prognostic biomarker in HCC. Functional assays assessed the role of B4GALT3 in proliferation, migration, invasion and ITGB1 glycosylation in HCC cells. Subsequently, enzyme-responsive 612-AYR nanoparticles were engineered to deliver a specific B4GALT3 inhibitor selectively to tumour sites. The nanoparticles' biocompatibility, tumour-targeting capability, retention and therapeutic efficacy were evaluated in both subcutaneous and orthotopic HCC mouse models. KEY RESULTS:B4GALT3 enhanced HCC cell proliferation, migration, and invasion by increasing ITGB1 glycosylation, stabilizing its protein level and activating downstream signalling and cell-cycle pathways. The 612-AYR nanoparticles demonstrated excellent biocompatibility, tumour-specific accumulation and prolonged retention in vivo. Treatment with these nanoparticles markedly suppressed tumour growth and metastasis in both mouse models through effective disruption of the B4GALT3-ITGB1 signalling axis. CONCLUSION AND IMPLICATIONS:Targeting aberrant glycosylation via enzyme-responsive 612-AYR nanoparticles delivering a B4GALT3 inhibitor presents a promising precision therapeutic approach for HCC. This integrated strategy combining glycosylation-targeted molecular biology and advanced nanotechnology offers a novel paradigm for personalized cancer treatment, holding significant therapeutic and diagnostic potential.

BackgroundHypomethylating agents, particularly azacitidine and decitabine, are widely used for the treatment of myelodysplastic syndromes and acute myeloid leukemia. Gastrointestinal adverse events and metabolism- and nutrition-related disorders may compromise nutritional intake, metabolic homeostasis, treatment tolerance, and clinical outcomes. However, real-world evidence regarding these safety profiles remains limited.ObjectiveThis study aimed to characterize gastrointestinal and metabolism- and nutrition-related adverse event reporting signals associated with azacitidine and decitabine, examine cross-database signal consistency, assess exploratory time-to-onset patterns, and explore potential mechanistic clues.MethodsFAERS reports from database inception through 2025 Q4 were analyzed for azacitidine and decitabine recorded as suspected drugs. Disproportionality was assessed at the preferred-term level using reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker methods. Selected signals were examined in the Canada Vigilance database for cross-database signal consistency. Exploratory time-to-onset patterns were evaluated using Weibull modeling among reports with valid date information, and network toxicology was conducted as a hypothesis-generating analysis.ResultsFourteen thousand two hundred sixteen azacitidine-related reports and 3,591 decitabine-related reports were included. Neutropenic colitis showed the strongest gastrointestinal disproportionality signal for azacitidine and decitabine, with reporting odds ratios of 23.65 and 26.05, respectively. Tumor lysis syndrome was the most prominent metabolism- and nutrition-related signal, with 165 azacitidine-related reports and 47 decitabine-related reports. Both signals showed consistent disproportional reporting patterns in the Canada Vigilance database. Additional signals included iron overload, hypoalbuminemia, electrolyte disturbances, cachexia, failure to thrive, and decreased appetite. Time-to-onset analysis suggested an early reporting tendency among reports with valid date information. Exploratory network toxicology identified 45 common targets, including MMP9, PTGS2, CASP3, GSK3B, and ADAM17, suggesting potential involvement of inflammation, apoptosis, matrix remodeling, nitrogen metabolism, folate biosynthesis, lipid metabolism, and insulin resistance pathways.ConclusionAzacitidine and decitabine showed clinically relevant gastrointestinal, metabolic, and nutrition-related disproportionality reporting signals in spontaneous reporting databases. Early monitoring of gastrointestinal symptoms, electrolyte balance, tumor lysis indicators, albumin levels, appetite, and iron metabolism may support nutritional risk management and individualized supportive care in patients receiving hypomethylating agents.

Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy with a poor prognosis, thus necessitating novel prognostic biomarkers and therapeutic targets. This study investigated the role of long non-coding RNAs (lncRNAs) in the pathogenesis and risk stratification of AML. Transcriptome sequencing was conducted on bone marrow samples from 20 patients with AML (10 low/intermediate-risk and 10 high-risk), revealing 344 differentially expressed lncRNAs and 1,109 dysregulated mRNAs. The application of functional enrichment analysis revealed that NF-κB signaling activation and Th17 cell differentiation represent the key pathways associated with high-risk AML. Among dysregulated lncRNAs, RNase P RNA Component H1 (RPPH1) demonstrated significant upregulation in patients with high-risk AML, thus establishing it as a promising candidate for further investigation. Functional validation employing AML cell lines MV-4-11 and MOLM13 demonstrated that RPPH1 overexpression enhanced cell proliferation and suppressed apoptosis, whereas its knockdown resulted in opposite effects. Mechanistically, RPPH1 enhanced NF-κB p65 phosphorylation and upregulated IL-17 A expression, thereby activating downstream oncogenic targets, including PLAC8, LRP12, and CRABP2. The present findings suggest that RPPH1 regulates AML progression via the NF-κB/Th17A signaling axis, providing new insights into its role in disease pathogenesis and immune microenvironment remodeling. In view of its prognostic and therapeutic potential, RPPH1 can function as both a biomarker and a promising therapeutic target for high-risk AML.

Extracellular Vesicles (EVs) have emerged as a focal point in research concerning material-related immune responses and osteogenesis. While previous studies have linked EVs in cerebrospinal fluid (CSF) to neurodegenerative diseases, our investigation reveals a novel perspective: CSF EVs possess the potential to stimulate osteogenesis, presenting a significant advancement. Thus, we explored the synergistic effects of cerebrospinal fluid-derived extracellular vesicles (CSF EVs) and deferoxamine (DFO), another osteogenic factor, within a hydrogel scaffold for bone regeneration. The composite scaffolds doped EVs and DFO (EDGP scaffold) exhibited remarkable outcomes, including enhanced differentiation of M2 macrophages, increased angiogenesis, and heightened osteoblast differentiation. We elucidated the underlying mechanism wherein CSF EVs might facilitate mesenchymal stem cells’ osteogenesis via the JAK1/STAT3 pathway. Upon implantation at the bone defect site, the EDGP scaffold demonstrated superior efficacy in fostering new bone formation, evident by elevated levels of osteoblastic differentiation markers and enhanced calcium nodule formation. This personalized treatment model has great potential to be integrated into neurosurgical interventions for individualized skull defect correction, leveraging the unique regenerative potential of EVs derived from the patient’s own cerebrospinal fluid in combination with biomimetically scaffolds to improve bone regeneration by avoiding immune rejection, size differences, and limited bone donors.

Syringetin inhibits bone metastasis in cancer, but its action in breast cancer-related bone pain is unknown. This study aims to analyze the action of Syringetin in breast cancer-related bone pain. Based on network pharmacology analysis, estrogen receptor 1 (ESR1) was identified as the core gene between Syringetin and bone pain associated with breast cancer, with the binding energy of -7.5 kcal/mol to ESR1 protein. Syringetin exhibited a dose-dependent inhibition of breast cancer cell viability, suppressed cell migration and expression of ESR1 and PRDM2 protein, and promoted cell apoptosis. In the Syringetin intervention group of rats, the bone trabeculae and cortical bone were slightly intact, along with an elevation in AS and PWT scores, a decrease expression of ESR1 and PRDM2 proteins. There was a clearly positive correlation between ESR1 protein and the GFAP, IBA1, and NeuN levels. Syringetin alleviated the disease characteristics of breast cancer-related bone pain by downregulating the ESR1/PRDM2 proteins.

Despite advances in chemoradiotherapy and hematopoietic stem cell transplantation, the treatment of acute myeloid leukemia (AML) remains challenging due to significant side effects and poor prognosis. This study aimed to investigate the role of nuclear factor I-C (NFIC) in AML progression by evaluating whether NFIC exacerbates AML through the inhibition of SRY-box transcription factor 1 (SOX1) and activation of autophagy, thereby providing potential insights for clinical treatment. NFIC and SOX1 expression levels in AML and normal samples were analyzed using bioinformatics, ELISA, RT-qPCR, and western blotting, and the interaction between NFIC and SOX1 was assessed through RNA pull-down and RNA-binding protein immunoprecipitation assays. Moreover, CCK-8 assay, FITC/PI apoptosis detection, immunofluorescence staining, RT-qPCR, and western blotting were conducted to assess cell viability, apoptosis, and the expression of NFIC, SOX1, Bax, Bcl-2, LC3-I, LC3-II, p62, and Beclin-1 following gene transfection. NFIC expression was significantly upregulated in AML samples while SOX1 expression was downregulated compared to normal controls. High NFIC levels were associated with poor prognosis in AML patients, and it was found to regulate SOX1 expression in KG-1 and NB4 cells negatively. Silencing NFIC or overexpressing SOX1 resulted in reduced cell viability and autophagy, and increased apoptosis in KG-1 and NB4 cells. Importantly, NFIC knockdown did not affect apoptosis in bone marrow mononuclear cells. The adverse effects of NFIC overexpression were reversed by SOX1 overexpression, highlighting the interplay between these factors in AML. This study demonstrates that NFIC promotes AML progression by activating autophagy and suppressing apoptosis in KG-1 and NB4 cells by inhibiting SOX1, providing a potential basis for therapeutic strategies targeting NFIC and SOX1 in AML.

PURPOSE:To develop an integrative radiopathomic model based on deep learning to predict overall survival (OS) in locally advanced nasopharyngeal carcinoma (LANPC) patients. MATERIALS AND METHODS:A cohort of 343 LANPC patients with pretreatment MRI and whole slide image (WSI) were randomly divided into training (n = 202), validation (n = 91), and external test (n = 50) sets. For WSIs, a self-attention mechanism was employed to assess the significance of different patches for the prognostic task, aggregating them into a WSI-level representation. For MRI, a multilayer perceptron was used to encode the extracted radiomic features, resulting in an MRI-level representation. These were combined in a multimodal fusion model to produce prognostic predictions. Model performances were evaluated using the concordance index (C-index), and Kaplan-Meier curves were employed for risk stratification. To enhance model interpretability, attention-based and Integrated Gradients techniques were applied to explain how WSIs and MRI features contribute to prognosis predictions. RESULTS:The radiopathomics model achieved high predictive accuracy in predicting the OS, with a C-index of 0.755 (95 % CI: 0.673-0.838) and 0.744 (95 % CI: 0.623-0.808) in the training and validation sets, respectively, outperforming single-modality models (radiomic signature: 0.636, 95 % CI: 0.584-0.688; deep pathomic signature: 0.736, 95 % CI: 0.684-0.810). In the external test, similar findings were observed for the predictive performance of the radiopathomics, radiomic signature, and deep pathomic signature, with their C-indices being 0.735, 0.626, and 0.660 respectively. The radiopathomics model effectively stratified patients into high- and low-risk groups (P < 0.001). Additionally, attention heatmaps revealed that high-attention regions corresponded with tumor areas in both risk groups. CONCLUSION:The radiopathomics model holds promise for predicting clinical outcomes in LANPC patients, offering a potential tool for improving clinical decision-making.

Spermatogonial stem cells (SSCs) play a crucial role in the male reproductive system, responsible for maintaining continuous spermatogenesis. The microenvironment or niche of SSCs is a key factor in regulating their self-renewal, differentiation and spermatogenesis. This microenvironment consists of multiple cell types, extracellular matrix, growth factors, hormones and other molecular signals that interact to form a complex regulatory network. This review aims to provide an overview of the main components of the SSCs microenvironment, explore how they regulate the fate decisions of SSCs, and discuss the potential impact of microenvironmental abnormalities on male reproductive health.

PurposeOsteolysis is a common complication in patients with multiple myeloma (MM). Our previous studies have demonstrated that MM cells can promote osteoclast differentiation of macrophages. In this study, we explored the effect of sulforaphane (SFN), a natural NRF2 activator found in broccoli, on MM cell-induced osteoclast differentiation.MethodsConditional medium (CM) derived from MM cells was used to induce osteoclast differentiation, and TRAP staining was performed to examine osteoclast. Gene expression was detected by western blotting or real-time PCR. Cell counting and EdU staining were performed to test macrophage proliferation.ResultsWe showed that the CM of MM cells downregulated the expression of ferroportin1 (Fpn1), the only known iron exporter in vertebrate cells, thereby increasing cellular iron levels in murine macrophage cells RAW264.7. Deferoxamine (DFO), an iron chelator, effectively blocked MM cell CM-induced osteoclast differentiation and macrophage proliferation, suggesting that iron overload played a key role in these cellular events. Subsequent mechanistic investigations revealed that MM cell CM induced osteoclast differentiation and macrophage proliferation by activating the JNK/AP-1/NFATC1 pathway and PI3K/AKT pathway. SFN was found to increase Fpn1 expression, leading to decreased cellular iron levels in RAW264.7 cells activated by MM cell CM. Importantly, the osteoclast differentiation and macrophage proliferation induced by MM cell CM were significantly inhibited by SFN.ConclusionAltogether, our findings indicated that SFN inhibits MM cell-induced osteoclast differentiation and macrophage proliferation by elevating FPN1 levels. SFN could be a promising therapeutic strategy for MM-associated osteolysis.

The partner of NOB1 homolog (PNO1) is an RNA-binding protein that participates in ribosome biogenesis and protein modification. The functions of this molecule are largely unknown in cancers, particularly breast cancer. We employed bioinformatics methods to probe the putative oncogenic functions of PNO1 based on expression profiles and clinical data from the cancer genome atlas (TCGA), genotype-tissue expression project (GTEx), human protein atlas (HPA), cancer cell line encyclopedia (CCLE), UALCAN, drug sensitivity in cancer (GDSC) and UCSC XENA databases. Our analyses revealed that PNO1 was overexpressed in 31 malignancies, which excluded kidney chromophobe (KICH) and acute myeloid leukemia (LAML). Prognostic assessments have demonstrated that high PNO1 expression was significantly correlated with poor overall and disease-specific survival in various cancers. The promoter methylation level of PNO1 is significantly decreased in breast invasive carcinoma (BRCA), head and neck squamous cell carcinoma (HNSC), kidney renal papillary cell carcinoma (KIRP), prostate adenocarcinoma (PRAD), thyroid carcinoma (THCA) and uterine corpus endometrial carcinoma (UCEC). Furthermore, inhibition of PNO1 decreased the viability, migration and invasion of breast cancer cells, and these results were confirmed by mouse xenograft models of breast cancer. In addition, we discovered that tumor microenvironment (TME), immune infiltration, and chemotherapy sensitivity were influenced by PNO1 expression. Concordantly, our analyses revealed a significant positive correlation between PNO1 and programmed cell death ligand 1 (PD-L1) expression across breast carcinoma samples. In conclusion, these findings indicate that PNO1 could act as a promising prognostic biomarker and adjunct diagnostic indicator, because it affects tumor growth and invasion. Our study offers valuable new perspectives on the oncogenic role of PNO1 in various types of cancers.

Background: Progress in improving risk stratification methods for patients with cytogenetically normal acute myeloid leukaemia (CN-AML) remains limited. This study investigates the prognostic significance and potential functional mechanism of malic enzyme 1 (ME1) in CN-AML. Methods: Gene expression and clinical data of patients with CN-AML were obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, which were subjected to analysis. The prognostic significance of ME1 was assessed through Kaplan-Meier survival analysis, as well as univariate and multivariate Cox regression analyses. A novel risk model based on ME1 expression levels was developed using TCGA data for predicting CN-AML prognosis. Furthermore, the impact of ME1 silencing on AML cell lines was investigated using the Cell Counting Kit-8 assay and flow cytometry. Gene set enrichment analysis (GSEA) analysis and Western blotting were performed to explore the mechanism of ME1 in CN-AML. Results: CN-AML patients expressing higher ME1 levels exhibited shorter event-free survival (EFS) and overall survival (OS) compared to those with lower ME1 expression in the TCGA and multiple GEO datasets (all p < 0.05). Univariate and multivariate Cox regression analyses indicated that ME1 expression served as an independent prognostic factor for the EFS (p = 0.024 in TCGA, p = 0.035 in GSE6891) and OS (p = 0.039 in TCGA, p = 0.008 in GSE6891) in patients with CN-AML. The developed risk model demonstrated that patients with CN-AML in the high-risk group had worse survival than those in the low-risk group (hazard ratio: 2.67, 95% confidence interval: 1.54-4.65, p < 0.001) and exhibited strong predictive accuracy for 1-, 3- and 5-year OS (area under the curve = 0.69, 0.75, 0.79, respectively). ME1 knockdown significantly inhibited proliferation and increased apoptosis in AML cells (all p < 0.05). GSEA and Western blotting demonstrated that ME1 regulates the IL-6/JAK2/STAT3 pathway in CN-AML. Conclusion: Elevated ME1 expression serves as an indicator of poorer prognosis in patients with CN-AML, potentially facilitating leukaemogenesis through the IL-6/JAK2/STAT3 pathway. This suggests that ME1 could be a promising prognostic biomarker and therapeutic target for CN-AML.

IntroductionLong non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) is confirmed to be involved in regulation of the multiple myeloma (MM) process. However, its underlying molecular mechanism deserves further investigation.Material and methodsQuantitative real-time PCR was used to examine NEAT1, microRNA (miR)-133a and actin-related protein 2/3 complex subunit 5 (ARPC5) expression. Cell proliferation and apoptosis were evaluated by cell counting kit 8 assay, soft-agar colony formation assay and flow cytometry. Dual-luciferase reporter assay was used to confirm the interaction between miR-133a and NEAT1 or ARPC5. The localization of NEAT1 and miR-133a in MM cells was determined by fluorescent in situ hybridization assay. In addition, animal experiments were conducted to explore the effect of NEAT1 knockdown on MM tumor growth in vivo.ResultsNEAT1 had increased expression in MM patients and cells. NEAT1 knockdown could repress MM cell proliferation and enhance apoptosis. NEAT1 could sponge miR-133a, and miR-133a could target ARPC5. MiR-133a was lowly expressed and ARPC5 was highly expressed in MM patients. MiR-133a inhibitor could abolish the suppressive effect of NEAT1 knockdown on MM cell growth, and these effects also could be reversed by ARPC5 silencing.ConclusionsAnimal experiments showed that NEAT1 downregulation reduced MM tumor growth by regulating miR-133a/ARPC5 axis. NEAT1 facilitated MM progression through the regulation of miR-133a/ARPC5, which provided new evidence that NEAT1 was a potential therapeutic target for MM.

Background: A comprehensive evaluation between anti-PD-1 and anti-PD-L1 is critical for appropriate treatment choice in clinical practice. This study aimed at evaluating the efficacy and safety of anti-PD-1 and anti-PD-L1 agents.Methods: This meta-analysis was conducted through adjusted indirect comparison (PROSPERO number: CRD42023452639). Randomized controlled trials (RCT) comparing anti-PD-1/anti-PD-L1 and standard treatments in solid tumors were retrieved from systematic literature search in Pubmed, Embase, and Cochrane Central databases from January 1st 2000, to January 31st 2023, together with the latest major conferences. Eligible RCTs regarding anti-PD-1 and anti-PD-L1 treatments were matched as mirror groups according to the same population and study design. Hazard ratio (HR) for overall survival (OS), progression-free survival (PFS), and disease-free/event-free survival (DFS/EFS), and risk ratio (RR) for objective response rate (ORR) and adverse events (AE) were generated from indirect comparisons in each mirror groups and were pooled for overall meta-analysis.Findings: A total of 96 eligible RCTs were identified, encompassing 104 arms of 58,407 patients, which constructed 32 mirror groups. Patients receiving anti-PD-1 treatment exhibited improved OS (HR, 0·86, 95%CI, 0·82–0·90; P<0·001), PFS (0·85, 0·75–0·96; P=0·01), and DFS/EFS (0·81, 0·70–0·94; P=0·005) benefit in overall populations compared to those receiving anti-PD-L1 treatment, together with a higher ORR (RR, 1·12, 95%CI, 1·04–1·19; P=0·001). However, anti-PD-1 demonstrated a higher risk of treatment-related AEs (2·08, 1·60–2·69; P<0·0001), while had comparable safety profiles with anti-PD-L1 therapies in terms of treatment-related AEs and immune-related AEs.Interpretation: This meta-analysis revealed that anti-PD-1 exhibited better survival outcomes compared to anti-PD-L1 in solid tumors with comparable safety profiles except for a higher risk of discontinuation.Funding: This study is funded by the National Key Research and Development Program of China(2021YFA1201100).Declaration of Interest: The authors declare no potential conflicts of interest, except the employment of Qiaoxia Zhou, Guoqiang Wang, Jinyu Yang, Xiaoran Sun, Junjun Li, Yezhen Shi, Qingbo Wei, Jing Wang, Zhou Zhang, Yuzi Zhang, Shangli Cai in Burning Rock Biotech.

Cytotoxin-associated gene A (CagA) of Helicobacter pylori (Hp) may promote immune evasion of Hp-infected gastric cancer (GC), but potential mechanisms are still under explored. In this study, the positive rates of CagA and PD-L1 protein in tumor tissues and the high level of exosomal PD-L1 protein in plasma exosomes were significantly associated with the elevated stages of tumor node metastasis (TNM) in Hp-infected GC. Moreover, the positive rate of CagA was positively correlated with the positive rate of PD-L1 in tumor tissues and the level of PD-L1 protein in plasma exosomes, and high level of exosomal PD-L1 might indicate poor prognosis of Hp-infected GC. Mechanically, CagA increased PD-L1 level in exosomes derived from GC cells by inhibiting p53 and miRNA-34a, suppressing proliferation and anticancer effect of CD8+ T cells. This study provides sights for understanding immune evasion mediated by PD-L1. Targeting CagA and exosomal PD-L1 may improve immunotherapy efficacy of Hp-infected GC.

Table S3: all the antibodies used and sequences of probes for Linc01060 RNA FISH.

Supplementary materials & methods and figure legends

Table S1: the sequences of relative siRNAs and shRNAs.

Gastric diffuse large B-cell lymphoma (GDLBCL) is a common disease with an increasing incidence. However, the regulatory effect of exosomal programmed death-ligand 1 (PD-L1) on the immune microenvironment in GDLBCL is unclear. In the present study, the protein expression levels of exosomal PD-L1 in the supernatants of cultured diffuse large B-cell lymphoma (DLBCL) cells and the plasma of patients with GDLBCL was assessed using immunoblotting. Exosomes derived from DLBCL cells were cocultured with T lymphocytes or injected into tumor xenograft mice by tail vein injection. The relationship between the protein expression level of exosomal PD-L1 in the plasma and the clinical characteristics and immune microenvironmental parameters of GDLBCL was evaluated using immunoblotting and immunohistochemistry. High levels of exosomal PD-L1 were found in the supernatants of cultured DLBCL cells. Exosomes with high levels of PD-L1 promoted growth of tumors formed by DLBCL cells in vivo and inhibited the proliferation of T lymphocytes. Notably, the protein expression level of PD-L1 in plasma exosomes derived from GDLBCL patients was significantly higher than that of healthy individuals. High levels of PD-L1 in plasma exosomes were significantly associated with international prognostic index score, pathological type and advanced Lugano stage, which might lead to the poor prognosis of GDLBCL. Moreover, a high level of PD-L1 in plasma exosomes was significantly associated with an immunosuppressive microenvironment in GDLBCL. Therefore, the results of the present study indicated that exosomal PD-L1 inhibited the proliferation of T lymphocytes and promoted the formation of an immunosuppressive microenvironment in GDLBCL. High expression of exosomal PD-L1 may suggest a poor prognosis of GDLBCL, and exosomal PD-L1 in plasma may be a new diagnostic indicator for GDLBCL.

Supplementary Tables 6: Correlation of the expression levels of Linc01060 in glioma tissues with clinicopathologic features.