Polysaccharides from Lycium barbarum L., particularly LBP3, exhibit immunomodulatory and anti-tumor properties, yet their active constituents remain unclear. Here, LBP3 was fractionated into PolyA, PolyB, and PolyC. PolyC emerged as the key bioactive component, enhancing phagocytosis in vitro and showing superior anti-tumor efficacy to PolyA in vivo (125 mg/kg). Mechanistically, PolyC upregulates gp91 and p47 expression involving Dectin-1, driving M2 macrophages toward an M1 phenotype and enhancing antigen presentation and adaptive immunity. Purification of PolyC yielded its major subfraction, PolyD, which was structurally characterized as a predominant α-(1 → 4)-linked glucan with α-(1 → 6)-branching and a terminal β-linkage. Despite its α-configuration, PolyD retains Dectin-1 agonistic activity, suggesting that Dectin-1 may recognize specific α-glucan conformations. In summary, this study establishes PolyC as the key bioactive component of LBP3 and PolyD as its structurally defined α-glucan, demonstrating that PolyC's anti-tumor activity involves Dectin-1-mediated NOX2 upregulation in TAMs, expanding the chemical diversity of Dectin-1 agonists and informing immunotherapy design.

e20597 Background: Immune checkpoint inhibitors (ICIs) have transformed treatment for advanced non-small cell lung cancer (NSCLC), but clinical effectiveness remains variable. Altitude may modulate host immunity and treatment responses. This study investigated the association between residential altitude and outcomes, and explored potential mechanism. Methods: This is a retrospective cohort study across 11 medical centers in China. Patients with advanced NSCLC receiving ICIs were classified by residential altitude: low-altitude ( < 1000m), middle-altitude (1000-2000m) and high-altitude ( > 2000m). Endpoints included progression-free survival (PFS) and overall survival (OS). Landmark and restricted mean survival time (RMST) analyses were employed due to violation of proportional hazards assumptions. Propensity score matching (PSM) and Cox regression addressed confounding. Tumor immune profiles were characterized by RNA sequencing and multiplex immunohistochemistry. Results: A total of 1793 patients were included: low-altitude (n = 1024), middle-altitude (n = 342), and high-altitude (n = 427). Median PFS was 11.2 months in low-altitude groups, 14.7 months in middle-altitude and 13.4 months in high-altitude. 2-years landmark analyses demonstrated improved PFS in both middle-altitude (HR = 0.78, 95%CI 0.65-0.93, P = 0.0058) and high-altitude (HR = 0.77, 95%CI 0.65-0.91, P = 0.0018) groups versus the low-altitude group, with no difference between the former two. Thus, we pooled these into a single M-H (middle-high) altitude group (n = 769). In PSM cohort, RMST analysis showed sustained PFS benefit with M-H altitude at 1 year (0.79 months, P = 0.0002), 2 years (1.70 months, P = 0.0007), and 3 years (1.88 months, P = 0.0171). Multivariable Cox regression during the first 2 years confirmed lower progression risk with M-H altitude (HR 0.78, 95%CI 0.68-0.89, P = 0.0003). OS benefit was significant at 1-2 years but attenuated by year 3. Further analyses demonstrated PFS and OS benefit with M-H altitude in most subgroups. RNA sequencing (n = 124) revealed higher effector cell and lower suppressor cell immunophenoscores with M-H altitude. Immunohistochemistry (n = 172) demonstrated increased tissue-resident memory CD8 + T cell infiltration associated with improved outcomes. Conclusions: M-H altitude residence is independently associated with improved clinical outcomes in advanced NSCLC patients receiving ICIs. This is supported by enhanced effector immune signatures and tissue-resident memory CD8 + T cell infiltration in tumors from M-H-altitude residents.

Polysaccharides from Lycium barbarum L., particularly the LBP3 fraction, exhibit immunomodulatory and anti-tumor properties, yet their active constituents and mechanisms remain unclear. Here, LBP3 was fractionated into three subfractions: PolyA (200–350 kDa), PolyB (100–200 kDa), and PolyC (40–100 kDa). In vitro assays showed that all fractions induced macrophage activation, but PolyC uniquely exhibited potent phagocytosis-enhancing activity. In a murine hepatocellular carcinoma model, PolyC exhibited superior in vivo anti-tumor efficacy compared to PolyA, even at a lower dosage. Mechanistically, PolyC activates the NADPH oxidase pathway by acting on the Dectin-1 receptor on macrophages, thereby reprogramming macrophages from M2 phenotype to M1 phenotype. This phenotypic shift enhanced phagocytic and antigen-presenting capacities, thereby triggering adaptive immune activation. Subsequent purification of PolyC yielded its major active subfraction, designated PolyD. Structural analysis revealed that PolyC and PolyD both are primarily composed of glucose residues linked via β-glycosidic bonds, which may constitute a key structural determinant for Dectin-1 recognition. In summary, this study identifies PolyC as the key bioactive component of LBP3, characterizes its structural features, and elucidates the molecular mechanism by which it reprograms tumor-associated macrophages (TAMs) via the Dectin-1/NADPH oxidase pathway. These findings provide a theoretical foundation for the development of polysaccharide-based tumor immunotherapies.

Quercetin (Quer), a naturally occurring flavonoid, has received significant attention because of its antitumor effectiveness and ability to synergistically enhance chemotherapy-induced effects by counteracting drug resistance. Ovarian cancer (OC) is a highly aggressive malignancy characterized by frequent chemoresistance, yielding treatment failure and recurrence, whereas effective strategies are lacking. This study elucidated the mechanisms underlying the anti-OC effects of Quer. Network pharmacology analysis revealed that the overlapping targets of Quer and OC are associated with oxidative stress. In vitro experiments indicated that Quer inhibited OC cell proliferation and induced canonical ferroptotic features, including shrunken mitochondria, labile Fe2+ overloading, increased lipid peroxidation, mitochondrial membrane potential loss, GSH depletion, and increased MDA levels. Ferrostatin-1 reversed Quer-induced cytotoxicity and ferroptotic phenotypes. Transcriptomic analysis and expression validation revealed NRF2/HO-1/GPX4 axis suppression. Molecular docking captured the stable binding of Quer to NRF2, HO-1, GPX4, and FTH1. NRF2 overexpression partially restored downstream antioxidant defenses but was insufficient to counteract Quer effects, indicating pathway dependence. In vivo, Quer reduced tumor growth and increased cisplatin (DDP) effectiveness without overt hepatorenal histopathology. This study is the first to reveal that Quer induces ferroptosis in OC cells at least partially through NRF2/HO-1/GPX4 antioxidant axis suppression and cisplatin effectiveness enhancement. These findings support further evaluation of Quer as a ferroptosis-priming adjunct to platinum-based OC therapy.

Lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) are two common subtypes of non-small cell lung cancer (NSCLC). This study investigates the potential of OIP5-AS1 as a biomarker in relation to these two NSCLC subtypes. By analysing OIP5-AS1 expression levels, its diagnostic and prognostic value, and associated clinical outcomes using the UCSC database, we observed differential expression patterns of OIP5-AS1 with upregulated in LUSC and downregulated in LUAD. OIP5-AS1 shows a positive correlation with tumour purity in both subtypes. Furthermore, it exhibits a negative correlation with tumour mutational burden (TMB) in LUSC and tumour heterogeneity in LUAD. Notably, OIP5-AS1 serves as a significant predictor for clinical stage IV in LUAD. In vitro experiments were conducted by transfecting an OIP5-AS1 overexpression plasmid into A549 cells, revealing that increased OIP5-AS1 expression significantly enhances the migratory capacity of these cancer cells. These findings highlight the significance of OIP5-AS1 as a promising biomarker and provide insights into its potential application in improving diagnosis and guiding personalised treatment strategies in LUAD and LUSC within the broader context of NSCLC management.

PURPOSE:To evaluate the performance of magnetic resonance imaging (MRI)-based artificial intelligence (AI) in the preoperative prediction of microvascular invasion (MVI) in patients with hepatocellular carcinoma (HCC). METHODS:A systematic search of PubMed, Embase, and Web of Science was conducted up to May 2025, following PRISMA guidelines. Studies using MRI-based AI models with histopathologically confirmed MVI were included. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Statistical synthesis used bivariate random-effects models. RESULTS:Twenty-nine studies were included, totaling 2838 internal and 1161 external validation cases. Pooled internal validation showed a sensitivity of 0.81 (95% CI: 0.76-0.85), specificity of 0.82 (95% CI: 0.78-0.85), diagnostic odds ratio (DOR) of 19.33 (95% CI: 13.15-28.42), and area under the curve (AUC) of 0.88 (95% CI: 0.85-0.91). External validation yielded a comparable AUC of 0.85. Traditional machine learning methods achieved higher sensitivity than deep learning approaches in both internal and external validation cohorts (both P < 0.05). Studies incorporating both radiomics and clinical features demonstrated superior sensitivity and specificity compared to radiomics-only models (P < 0.01). CONCLUSIONS:MRI-based AI demonstrates high performance for preoperative prediction of MVI in HCC, particularly for MRI-based models that combine multimodal imaging and clinical variables. However, substantial heterogeneity and low GRADE levels may affect the strength of the evidence, highlighting the need for methodological standardization and multicenter prospective validation to ensure clinical applicability.

Aims Patchouli essential oil (PEO) is the major active ingredient of a famous medicinal plant Pogostemon cablin (Blanco) Benth. This study aims to investigate the anti-aging activities of PEO and its major component, and elucidate the underlying molecular mechanisms. Main methods The anti-aging activities of PEO and its main component patchouli alcohol (PA) were investigated by examining the lifespan, senescence associated indicators as well as stress resistance of Caenorhabditis elegans. RNA-Sequencing was performed to analyze differentially expressed genes and the enrichments of GO and KEGG pathways in nematodes treated with PEO. The potential anti-aging target was predicted using a network pharmacology method and molecular docking. The underlying mechanism of senescence-delaying action was explored using C. elegans mutants and GFP transgenic strains. Key findings PEO modulated lifespan and healthspan extension of worms, ameliorated the senescence characterizations, and increased the survival in stress resistance assays. PEO reduced spawning, lipid accumulation and reactive oxygen species (ROS) levels of nematodes. The levels of anti-oxidative genes and proteins were obviously upregulated after PEO treatment. Moreover, PA was identified to be an ingredient for PEO-mediated nematode longevity. The JNK-1/DAF-16 signaling pathway played a critical role in PEO/PA-mediated longevity. Significance The findings revealed that PEO and its major component PA showed significant anti-aging activity through modulating the JNK-1/DAF-16 signaling pathway, which provides a promising strategy to treat aging and age-related diseases.

Solid tumors are characterized by extensive extracellular matrix (ECM) remodeling prominently featuring massive collagen deposition. This dense collagen network does not act as inert scaffolding but actively orchestrates critical aspects of tumor progression and therapy resistance, thereby shaping the fate of cancer cells. Collagen influences cellular behavior through multiple mechanisms, including providing structural rigidity, modulating mechanotransduction signaling pathways, creating physical barriers to immune cell infiltration and drug penetration, and serving as a reservoir for signaling molecules. Here, we discuss recent findings regarding the critical roles of collagen in tumors and potential therapies for armored and cold tumors, a refractory subset demonstrating high collagen deposition and low immune infiltration.

Cuproptosis, a newly discovered process of copper-dependent cellular demise, is initiated by the direct interaction of Cu2+ with lipoylated components within the mitochondrial tricarboxylic acid (TCA) cycle. This mechanism hinders cellular respiration and influences carcinogenesis, angiogenesis, and metastasis. The specific role of cuproptosis-related long non-coding RNAs (CRLs) in cervical cancer remains poorly understood. This research developed a predictive model using CRLs and investigated its potential molecular roles in the tumor microenvironment, as well as its influence on clinical outcomes in cervical cancer. We initially assessed putative CRLs from TCGA cervical cancer transcriptome data by linking cuproptosis regulators with lncRNA expression using Pearson correlation analysis. From 188 differentially expressed lncRNAs, univariate Cox and LASSO regression analysis developed a four-CRL prognostic model consisting of AC096992.2, MKLN1-AS, BAIAP2-DT, and LINC02356. Patients were categorized into two groups, high-risk and low-risk, based on a computed risk score. Multivariate Cox analysis, which included clinicopathological factors, confirmed substantial survival differences among these groups. Additionally, distinct profiles of immune checkpoint markers and tumor-infiltrating immune cells were discerned between the two cohorts. Our CRL model serves as an independent predictive tool for cervical cancer, deepens our understanding of CRL-mediated carcinogenesis, and provides valuable insights for the development of novel therapeutic options.

Dishevelled-associated activator of morphogenesis1 (DAAM1) is a member of the evolutionarily conserved Formin family and plays a significant role in the malignant progression of various human cancers. This study aims to explore the clinical and biological significance of DAAM1 in pancreatic cancer. Multiple public datasets and an in-house cohort were utilized to assess the clinical relevance of DAAM1 in pancreatic cancer. The LinkedOmics platform was employed to perform enrichment analysis of DAAM1-associated molecular pathways in pancreatic cancer. Subsequently, a series of in vitro and in vivo experiments were conducted to evaluate the biological roles of DAAM1 in pancreatic cancer cells and its effects on intratumoral T cells. DAAM1 was found to be upregulated in pancreatic cancer tissues, with higher expression levels observed in tumor cells. Additionally, high expression of DAAM1 was associated with poor prognosis. DAAM1 acted as an oncogene in pancreatic cancer, and its inhibition suppressed tumor cell proliferation, migration, and invasion, while promoted apoptosis. Furthermore, DAAM1 was involved in the JAK1/STAT1 signaling pathway and regulated PD-L1 expression in pancreatic cancer cells. The inhibition of DAAM1 also significantly reduced the exhaustion levels of CD8+ T cells. In conclusion, DAAM1 functions as an oncogene and is immunologically implicated in pancreatic cancer, these findings suggest that DAAM1 may serve as a promising therapeutic target for the clinical management of pancreatic cancer.

Ovarian aging is closely associated with a decline in fertility and an increase in reproductive dysfunction. Ovarian granulosa cells (GCs) support oocyte homeostasis and development, yet insight into GC dysfunction during aging is limited. Here, we show that aged GCs of humans and mice have indications of elevated ferroptosis, including increased ferroptosis-related metabolites, lipid peroxidation, and iron accumulation. The ferroptosis inhibitor Ferrostatin-1 reversed ovarian impairment and fertility of aged mice in vivo . We show that the age-related reduction in the expression of TXN (thioredoxin) leads to ferroptosis in human and mouse GCs by blocking BNIP3L-dependent mitophagy. Exogenous activation of TXN could promote mitophagy, thereby clearing excessive ROS and inhibiting ferroptosis. These results suggest that anti-ferroptosis-related treatments may assist in treating aging-related reproductive disorders. ![Figure][1] Key points ### Competing Interest Statement The authors have declared no competing interest. [1]: pending:yes

Breast cancer is a heterogeneous disease with a high incidence, but its proteomes have not yet been thoroughly characterized. To construct a comprehensive dynamic network of breast cancer-related proteins, we integrated the whole-cell proteome (WCP), phospho-proteome, malonyl-proteome of breast cancer tumor tissues and adjacent healthy tissues. We identified 2,417 differentially expressed proteins (DEPs), 646 differentially phosphorylated proteins (DPPs), and 107 differentially malonylated proteins (DMPs). Functional enrichment analysis revealed that these differentially expressed proteins are involved in extracellular matrix (ECM) interactions and immune-related pathways. Protein‒protein interaction (PPI) analysis revealed posttranslational modification (PTM) crosstalk between proteins involved in phosphorylation and malonylation. The acetyltransferase EP300 and deacetylase HDAC1 are involved in the DPP network, whereas the phosphatase PKM is a hub protein in the DMP network. Kinase-substrate enrichment analysis (KSEA) revealed the activation of the kinases CSNK1D, ROCK1, ROCK2, and CDK2. Overall, this study provides a foundation for understanding the functions of phosphorylation and malonylation in breast cancer. It systematically reveals critical features of breast cancer, providing a resource for exploring PTM crosstalk within and across proteins involved in the disease.

Anthracycline-based chemotherapy, while foundational in breast cancer treatment, confers substantial cardiotoxicity. Identifying biomarkers to guide anthracycline exemption without compromising efficacy has remained an unresolved clinical challenge for decades. We conducted multi-cohort spatial-omics and clinical validation integrating 345 early-stage triple-negative breast cancer (eTNBC) and 167 HER2 + breast cancer patients from Fudan University Shanghai Cancer Center (FUSCC) cohorts, alongside 150 eTNBC patients from a validation cohort. Tumor-specific MHC-II (tsMHC-II) expression was quantified via multiplex immunohistochemistry (mIHC). Mechanistic insights were derived from the NeoTRIP immunotherapy spatial cohort, I-SPY2 trial data, TCGA database, ATAC-seq chromatin profiling, ChIP, and patient-derived organoid (PDO)-immune cell co-culture systems. In eTNBC, high tsMHC-II expression predicted improved disease-free survival (DFS) and comparable overall survival (OS) with paclitaxel-carboplatin (PCb) versus anthracycline-sequential paclitaxel (EC-P), identifying tsMHC-II as a predictive marker for anthracycline exemption. High tsMHC-II correlated with prolonged DFS and OS in both TNBC and HER2 + subtypes. Multi-omics including spatial and transcriptional cohorts revealed tsMHC-II-high tumors harbor immune-rich microenvironments with elevated cytotoxic T cells, B cells, and antigen-presenting cells. Validation in NeoTRIP and I-SPY2 cohorts demonstrated superior immunotherapy response in tsMHC-II-high patients. Mechanistically, ATAC-seq, ChIP and PDO co-culture models confirmed that KAT2B upregulated tsMHC-II via CIITA promoter acetylation, sustaining immunotherapeutic vulnerability. TsMHC-II serves as a dual biomarker for adjuvant anthracycline chemotherapy exemption and neoadjuvant immunotherapy stratification in TNBC, driven by KAT2B-mediated epigenetic remodeling. These findings advance precision strategies to reduce anthracycline toxicity while enhancing immune activation in eTNBC.

Triple-negative breast cancer (TNBC) has no expression on estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), resulting in an ineffective treatment using current therapeutic therapies. As a heterogeneous disease, the notable refractory, high recurrence rate and unfavorable prognosis facilitate some researches to further elaborate novel insights into the biology of TNBC and formulate the precision treatment. Ferroptosis is a unique regulated-cell-death modality characterized by the excessive accumulation of the lipid peroxides on cellular membranes in an iron-dependent manner. Resveratrol (RES), a natural antioxidant that possesses biological activities, has various potential benefits for many diseases through regulating the cell activity. RES has been reported to markedly inhibit the tumor progression, yet its role in ferroptosis pathway of TNBC and the underlying mechanism remain unclear. In this study, we found that RES suppressed cell viabilities, consisting of cell migration, cell colony formation, and induced the cell apoptosis, along with mitochondrial structure damage, intracellular iron overload, increasing reactive oxygen species (ROS) and lipid peroxidation accumulation, malondialdehyde (MDA) production, and glutathione (GSH) depletion, interestingly, which was reversed by ferroptosis inhibitors. Next, the protein level of GPX4 was significantly suppressed in RES-treated TNBC cells in vitro and in vivo, facilitating the cancer cell ferroptosis. Our data confirm that RES suppresses GPX4 protein by increasing the NEDD4L-mediated ubiquitination attributed from the enhanced interactions between NEDD4L and GPX4 through the inhibition of the ERK1/2/SGK1/NEDD4L/GPX4 pathway in vitro and in vivo. In conclusion, our study identified the mechanism by which RES could exert ferroptosis in TNBC, finally providing a novel strategy for TNBC treatment.

2530 Background: The effect of non-steroidal anti-inflammatory drugs (NSAIDs) on immune checkpoint inhibitors (ICIs) efficacy in non-small cell lung cancer (NSCLC) remains controversial. Although the COX-2/PGE2 pathway, a primary target of NSAIDs, has been implicated in diminished immunotherapy response, direct clinical association with NSAIDs and ICIs in real world has yet to be established. This study aims to evaluate the impact of NSAIDs use—considering types, duration, and timing—on ICI efficacy, alongside its effects on PGE2 and immune cell profiles. Methods: We included stage III-IV NSCLC patients receiving PD-1/PD-L1 antibodies in 5 centers. Blood and tumor samples were collected in perspective cohort. NSAIDs were categorized based on selectivity (non-selective COX inhibitors, selective COX-2 inhibitors) and chemical structure (salicylates, propionate derivatives, others). PGE2 and cytokines were measured in blood by ELISA. RNA sequencing data were obtained from databases. Tumor tissues were collected for immunohistochemical staining of immune cells. Multivariate Cox and logistic regression were used in analyses of progression-free survival (PFS) and objective response rate (ORR). Results: 883 patients were included, with 140 NSAIDs users and 743 non-users. 196 patients were enrolled prospectively with samples. Multivariate analysis showed that NSAIDs use was significantly associated with improved PFS (HR 0.67, 95% CI 0.51-0.88, P = 0.005) and ORR (OR 1.87, 95% CI 1.29-2.72, P = 0.001). Subgroup analyses indicated that non-selective COX inhibitors, salicylates, long-term use, and pre-ICI initiation were correlated with better outcomes. In contrast, selective COX-2 inhibitors, propionate derivatives, others, short-term use, and post-ICI initiation showed no effect on PFS or ORR. Blood analyses indicated that NSAIDs significantly lowered PGE2 levels, particularly salicylates and long-term use. Higher PGE2 was associated with worse outcomes. For immune cells, RNA sequencing revealed that COX-2 and mPGES-1 were significantly correlated with neutrophil enrichment and neutrophil-related cytokines. Single-cell RNA-seq showed high expression of COX-2 and mPGES-1 in neutrophils. Analysis of samples confirmed that NSAIDs use was associated with reduced neutrophils and neutrophil-related cytokines in blood and less neutrophil infiltration in tumor. Conclusions: NSAID use is an independent predictor of improved PFS and ORR in NSCLC patients receiving ICIs. Specifically, non-selective COX inhibitors, salicylates, long-term use, and pre-ICI initiation are associated with better clinical outcomes. NSAID use may enhance ICIs efficacy by reducing serum PGE2, which could serve as a predictive biomarker. Furthermore, NSAIDs decrease neutrophils in both blood and tumor, potentially contributing to the improvement in ICI efficacy.

This study developed a dual-network hydrogel patch loaded with Dictyophora indusiata β-glucans to enhance diabetic wound healing. The hydrogel combines a flexible primary network formed by polymerized sulfobetaine methacrylate with a rigid secondary alginate network crosslinked via metal ions. The resulting material demonstrates favorable mechanical properties for wound care, achieving 600 % elongation at break, 3.12 MPa compressive strength, and 1.5 kPa tissue adhesion strength. These characteristics meet with the physical requirements necessary for effective diabetic wound management. Furthermore, the β-glucans derived from Dictyophora indusiata, which serve as the main bioactive component, endowed the hydrogel patch with significant antioxidant and anti-inflammatory properties. Cellular experiments have demonstrated that the hydrogel patch significantly reduces reactive oxygen species levels in cells and inhibits inflammatory responses. In animal wound model, diabetic wound treated with a hydrogel patch achieved a closure rate of 98.26 % by the second week. Additionally, histological analyses revealed that the hydrogel patch significantly facilitates angiogenesis, collagen deposition, and re-epithelialization in diabetic wound. Consequently, the hydrogel patch based on β-glucans from Dictyophora indusiata appears to be an effective agent for promoting wound healing, thereby offering a novel therapeutic strategy for the repair of diabetic wound.

BackgroundThe aim of this network meta-analysis was to clarify the efficacy and safety of different immune checkpoint inhibitors (ICIs) in combination with chemotherapy in the neoadjuvant phase for the treatment of locally advanced esophageal cancer.MethodsWe searched PubMed, EMBASE, Web of Science, Cochrane Library, CNKI and WanFang databases from January 2000 until May 2024. The primary endpoints were pathological complete response (pCR), major pathological response (MPR), R0 resection rate, objective response rate (ORR), disease control rate (DCR), treatment-related adverse events(TRAEs) of any grade and TRAEs of grade 3 or higher. The Newcastle-Ottawa Scale (NOS) and the Cochrane Risk of Bias tool were used to evaluate risk of bias. To analyze the data, Review Manager 5.3 and Stata16.0 were applied.ResultsFourteen eligible studies (six randomized controlled trials) and 8 retrospective cohort studies) enrolling 1139 patients were included for this network meta-analysis. All studies originated from China. For patients with locally advanced esophageal cancer, neoadjuvant immunochemotherapeutic strategies showed significant advantages over traditional neoadjuvant therapy in terms of pCR, MPR, ORR and DCR. Among the analyzed regimens, camrelizumab plus chemotherapy demonstrated the most pronounced improvements in pCR and MPR, while pembrolizumab plus chemotherapy achieved the best outcomes in terms of ORR and DCR. There were no significant differences observed among the various neoadjuvant treatment strategies regarding R0 resection rate, any grade TRAEs, or grade≥3 TRAEs. The most common TRAEs in the neoadjuvant chemotherapy plus immunotherapy group were myelosuppression and gastrointestinal damage, with most grade 3 or higher TRAEs being hematologic adverse events. The most frequent immune-related adverse events(irAEs) included rash (4.2-21.7%), thyroid dysfunction (hypothyroidism or hyperthyroidism, 6.3-17.4%), and pneumonia (4.2-6.3%), with the majority being mild to moderate (grade 1 or 2).ConclusionsNeoadjuvant immunotherapy combined with chemotherapy regimens demonstrate relatively high efficacy and tolerable safety profiles. Among the evaluated regimens, the combination chemotherapy with camrelizumab had relatively high pCR and MPR, whereas the combination chemotherapy with pembrolizumab had relatively high ORR and DCR. There were no significant differences in safety among the various regimens. Our study suggests that evaluating the efficacy and safety of different ICIs may be helpful in clinical decision-making.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024583548.

Melanoma is the most suitable tumor type for immunotherapy, but not all melanoma patients could respond to immunotherapy. B7 homolog 3 (B7-H3) belongs to the B7 family and is overexpressed in a number of malignant tumors, but the expression pattern of B7-H3 in melanoma has not been well summarized. The expression of B7-H3 was investigated in melanoma and its correlations with features of the tumor microenvironment (TME) by using various public databases, including the Cancer Genome Atlas (TCGA), the GEPIA, and the Human Protein Atlas databases. In addition, the in-house melanoma tissue microarray was applied to validate the results from public databases. Based on the public and in-house cohorts, we found that B7-H3 was overexpressed in melanoma tumor tissues and high B7-H3 expression was related to poor clinical outcome. Moreover, B7-H3 was negatively correlated with levels of tumor-infiltrating lymphocytes (TILs) and positively correlated with collagen infiltration. With clinical translational value, the predictive value of B7-H3 for conventional immunotherapy was detected using the Kaplan-Meier plotter tool, and the results showed that melanoma patients with high B7-H3 expression were insensitive to anti-PD-1 and anti-CTLA-4 immunotherapy. In conclusion, we first investigate the expression of B7-H3 in melanoma and its correlations with the TME features, and indicate B7-H3 as a promising therapeutic target in melanoma patients that are insensitive to conventional immunotherapy.

Lung cancer is one of the most common types of malignant cancer worldwide, causing a serious social and economic burden. It is classified into non-small cell lung cancer (NSCLC) and small cell lung cancer, with NSCLC accounting for 80-85% of cases. Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) is highly expressed in NSCLC, playing an important role in regulating tumor growth, angiogenesis, malignant transformation, and phagocytosis. Ubiquitin-specific protease 10 (USP10) functions as a deubiquitinating enzyme to regulate substrate protein deubiquitination and reverse the ubiquitin proteasome degradation pathway. Our previous study identified an interaction between EIF4G1 and USP10; however, their regulatory mechanism remains unclear. Herein, we found that USP10 positively regulates EIF4G1 in NSCLC cells. An in vivo ubiquitination assay demonstrated deubiquitination of EIF4G1 by USP10, which reversed the ubiquitin proteasomal degradation of EIF4G1, thereby increasing its stability. Upregulation of EIF4G1 promoted cell proliferation, migration, and invasion in NSCLC cells. The current study not only reveals a novel mechanism through which USP10 positively regulates EIF4G1 in NSCLC, but also demonstrates the potential of USP10 as a therapeutic target to treat NSCLC.