B cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) exert their functions by engaging distinct receptors, B cell maturation antigen (BCMA), transmembrane activator and CAML interactor (TACI), and BAFF receptor (BAFFR), thereby regulating the differentiation and survival of specific B cell subsets. Humoral immune memory relies on two complementary reservoirs, long-lived plasma cells (LLPCs) and memory B cells (MBCs). They can be categorized from a developmental perspective into low-affinity, short-lived cells generated in a germinal center (GC)-independent manner, and high-affinity, long-lived cells that require GC reactions. As a key survival factor for B cells, the BAFF/APRIL system plays a critical regulatory role in maintaining these compartments. The memory reservoirs particularly in autoimmune disorders where B cells act as central pathogenic drivers, sustain autoreactive antibody pools and largely contribute to disease relapse. Following the success of BAFF/APRIL system targeted biologics, such as belimumab and telitacicept, and with BCMA-directed chimeric antigen receptor T (CAR-T) cell therapy recently showing remarkable efficacy in autoimmune diseases, novel treatment avenues have emerged for cases resistant to conventional B cell depletion strategies. We now recognize that while conventional B cell depletion effectively reduces the circulating B cells to achieve rapid disease control, therapeutic targeting of the BAFF/APRIL system addresses the survival of long-lived subsets such as LLPCs, thereby filling the gap left by depletion strategies and partially contributes to sustained immunological control. These distinctions highlight the rationale for sequential therapeutic strategies, reinforcing the translational potential of precision medicine in autoimmune disease management.

To investigate the feasibility and potential efficacy of “watchful waiting” strategy in IgG4-related disease (IgG4-RD) patients being asymptomatic or having low disease activity. IgG4-RD patients presented in our station between October 2018 to October 2022, who met the criteria for “watchful waiting” modified from the 2015 International Consensus Guidance Statement were included. Deidentified clinical laboratory data were retrospectively collected and statistically analyzed between patients undergone watchful waiting (“WAIT” group) and received routine medical treatments (“TREAT” group). Subgroup analyses in “WAIT” group were also performed to compare the features between patients with and without receiving surgical resection of involved organs. A total of 49 patients meeting the “watchful waiting” criteria were included and followed for a median of 48 [IQR 24.00, 48.00] months. The median IgG4-RD responder index (RI) of them was 2; 71.4

BACKGROUND:As a key downstream effector of the Hippo signaling pathway, Yes-associated protein (YAP) has emerged as a pivotal regulator of tumor immune evasion and resistance to immune checkpoint inhibitors (ICIs). However, the relationship between YAP expression and immunotherapy outcomes in patients with non-small cell lung cancer (NSCLC), as well as its potential value as a therapeutic target, remains to be systematically investigated. METHODS:We retrospectively analyzed 141 patients with NSCLC who received immunotherapy, including 9 monoimmunotherapy and 132 immunotherapy plus chemotherapy or anti-angiogenic therapy. The expression of YAP in tumor tissues was evaluated by immunohistochemistry, and the association between YAP expression and immunotherapy resistance was assessed. Gene expression profiling following YAPand transcriptional coactivator with PDZ-binding motif (TAZ) knockdown was performed to identify potential YAP inhibitors and explore their underlying mechanisms of action. Furthermore, the therapeutic potential of a YAP inhibitor in reversing ICI resistance was evaluated in two patients with high YAP expression who had developed acquired resistance to immunotherapy. RESULTS:In our cohort, which predominantly received combination immunotherapy (93.62%), high YAP expression was associated with poor clinical outcomes to immunotherapy. Notably, YAP expression outperformed Programmed Cell Death Ligand 1 (PD-L1) as a predictive biomarker for treatment response. Through screening for potential YAP inhibitors, tucidinostat (TD) was identified as a compound capable of suppressing YAP activity. In two elderly patients with advanced NSCLC who had developed acquired resistance to immunotherapy, the combination of TD with ICIs successfully restored antitumor responsiveness. Mechanistic investigations further revealed that TD suppressed YAP expression via SNAI2-mediated epigenetic regulation, thereby blocking YAP-dependent tumor proliferation and immune evasion. CONCLUSIONS:YAP is a strong predictive biomarker of response to immunotherapy in NSCLC. The combination of TD and ICIs shows promise in reversing immunotherapy resistance associated with high YAP expression, offering a potential strategy to overcome acquired resistance.

Autoimmune inflammatory rheumatic diseases (AIIRD) are systemic disorders characterized by breakdown of immune tolerance and production of pathogenic IgG autoantibodies, leading to chronic inflammation and tissue damage. The rapid and selective lowering of pathogenic IgG therefore has therapeutic appeal. The neonatal Fc receptor (FcRn) is a key regulator of IgG homeostasis, which mediates the IgG half-life extension and transportation across cell barriers, while also facilitating antigen presentation. Targeting FcRn offers a novel, precision medicine approach to reduce pathogenic IgG burden and regulate immunity without inducing broad immunosuppression. This review summarizes FcRn biology, discusses the therapeutic rationale for FcRn inhibition, maps the evolving pipeline of FcRn inhibitors, and integrates key preclinical and clinical evidence across rheumatic indications. It also addresses practical considerations for clinical implementation and pharmacoeconomics, together with future directions for the field. FcRn inhibition accelerates IgG catabolism and potentially dampens downstream inflammatory circuits by reducing immune-complex–mediated activation and related immune signaling. This rationale is supported by multiple preclinical models and emerging clinical data. Several FcRn-targeted agents, including efgartigimod, nipocalimab, and IMVT-1402, are currently in clinical development for various indications encompassing idiopathic inflammatory myopathies (IIM), Sjögren’s disease (SjD), systemic lupus erythematosus (SLE), and rheumatoid arthritis (RA). FcRn blockade represents a promising precision-medicine strategy for IgG-driven AIIRD. Future studies should define optimal patient populations, identify predictive biomarkers, optimize next-generation molecules, and clarify long-term safety, pharmacoeconomic value, and opportunities for indication expansion.

Neoadjuvant immunochemotherapy (nICT) has reshaped the treatment paradigm for locally advanced esophageal cancer (EC), but patient responses remain highly heterogeneous. Reliable biomarkers to predict therapeutic benefit are urgently needed. Class I human leukocyte antigen (HLA-I) molecules are essential for anti-tumor immunity, presenting neoantigens to cytotoxic T lymphocytes.This study investigated the relationship between germline HLA-I genotypes and treatment response in patients with esophageal cancer receiving nICT. We retrospectively analyzed 30 Chinese EC patients who underwent surgery following nICT. High-resolution sequencing was used to determine germline HLA-I genotypes. Associations between specific HLA alleles and both short-term pathologic response and long-term survival outcomes, including pathologic complete response (pCR) and event-free survival (EFS) were evaluated. HLA-A*11:01 carriers exhibited significantly prolonged EFS compared with non-carriers (P = 0.015). In contrast, the HLA-A*24:02 allele was more frequent in non-pCR patients (50.0

Background : Head and neck squamous cell carcinoma (HNSC) is a globally prevalent malignancy with high mortality rates. RNA-binding proteins (RBPs) are crucial regulators of gene expression and play significant roles in cancer development. However, a comprehensive understanding of RBPs at the single-cell level in HNSC remains limited. Objective This study aims to investigate the role of RBPs in the stepwise progression of HNSC at the single-cell level, focusing on their expression patterns, prognostic potential, and involvement in key signaling pathways. Methods We analyzed single-cell RNA-sequencing data from HNSC samples across four stages, from normal tissue to precancerous leukoplakia, then to primary cancer and finally to metastatic tumors, examining the expression of 2141 previously reported RBPs. We identified RBP-based cell clusters and explored their associations with disease stages, cell types, and cancer progression. A prognostic risk model was developed based on RBPs with significant relevance to patient outcomes. Results RBPs displayed distinct cell type-specific expression patterns across different stages of HNSC. We found a significant correlation between RBP-based cell clusters and cancer progression. Notably, a prognostic model was constructed using RBPs such as CELF2, which showed downregulation from early leukoplakia to advanced cancer stages. Fibroblast RBPs were dynamically regulated, particularly in extracellular matrix remodeling, with key proteins like CFL1 and PFN1 linked to improved prognosis. Furthermore, we identified heterogeneity in RBP regulation of the Macrophage Migration Inhibitory Factor (MIF) signaling pathway across cell types during the precancerous stage. Conclusions Our findings highlight the crucial roles of RBPs in HNSC progression and suggest their potential as therapeutic targets and prognostic markers, offering insights into personalized treatment strategies.

Radiotherapy is a standard cancer treatment that involves the induction of DNA damage. DNA damage repair (DDR) pathways maintain genomic integrity and make tumors resistant to radiotherapy and certain chemotherapies. In turn, DDR dysfunction results in cumulative DNA damage, leading to increased sensitivity for antitumor treatment. Moreover, radiotherapy has been shown to trigger antitumor immunity. Currently, immunotherapy has become a new and widely used standard strategy for treating a broad spectrum of tumor types. Notably, recent studies have demonstrated that DDR pathways play important roles in driving the response to immunotherapy. Herein, we review and discuss how DDR affects antitumor immunity induced by radiotherapy. Furthermore, we summarize the development of strategies for combining DDR inhibitors with radiotherapy and/or immunotherapy to enhance their efficacy against cancers.

OBJECTIVES:To investigate the effects of thalidomide in preventing disease relapse with 'zero' glucocorticoids (GCs) usage in IgG4-related disease (IgG4-RD). METHODS:This was a multicentre, randomised, double-blinded, placebo-controlled study, in which eligible patients in disease active status were randomised into 2 groups (group 1: GCs+Thalidomide; group 2: GCs+Placebo) at a 1:1 ratio. The primary outcome of this trial was the disease relapse rate at month 12, whereas the secondary outcomes were the disease remission rate at month 12 and the incidence of adverse events (AEs). RESULTS:A total of 60 patients were randomised, and 57 patients (GCs+Thalidomide: 29; GCs+Placebo: 28) finished the study per protocol. The relapse rates of the GCs+Thalidomide and GCs+Placebo groups at month 12 were 13.8% and 67.8%, respectively. A 100% response rate was observed in both treatment group, while the remission rates of the GCs+Thalidomide and GCs+Placebo groups were 75.8% and 32.1%, respectively. In total. 49 AEs were recorded in 35 participants, in which 4 were graded as moderate, and 45 were graded as mild. The risk-benefit analysis based on the evaluation of rates of disease relapse and moderate AEs within the 12-month follow-up showed a NNT (number needed to treat) of 2 and a NNH (number needed to harm) of 8 for thalidomide treatment. CONCLUSIONS:Thalidomide can effectively prevent relapse in IgG4-RD outweighing its side effects, which indicating that thalidomide can be a potential safe therapeutic option for disease relapse prevention in parallel with steroid sparing in IgG4-RD.

Immunoglobulin G4-related disease (IgG4-RD), first identified two decades ago, is an immune-mediated pro-inflammatory and profibrotic disease entity affecting multiple organs. The main histopathological features are a dense lymphoplasmacytic infiltrate rich in IgG4 + plasma cells, storiform fibrosis, and obliterative phlebitis. The precise immunopathology of IgG4-RD is still unclear. Substantial research has validated the central role of B cells in IgG4-RD, which can be further demonstrated by the responsiveness to B cell depletion treatment and the identification of multiple autoantibodies. Whether and how antibodies are pathogenic remains mechanistically undefined, warranting systematic investigation. Through integrative analysis of experimental studies and clinical findings, this review discussed the common characteristics of different classes of antibodies and their potential corresponding unique mechanisms involved in IgG4-RD. Despite belonging to distinct classes, antibodies share conserved structural features that mediate common effector functions including neutralization and opsonization. In IgG4-RD pathogenesis, the soluble IgG4 form appears non-pathogenic, whereas its membrane-bound counterpart demonstrates enhanced antigen-binding avidity and facilitates epitope spreading cascades. Among other IgG subclasses, IgG1 emerges as a more potentially pathogenic subclass of antibody. Emerging evidence from multidisciplinary investigations progressively delineates the pathogenetic contributions of IgE and IgM. Systematic interrogation of antibodies with different classes and their pathogenic mechanisms in IgG4-RD advances our understanding of disease immunopathogenesis while unveiling novel therapeutic targets with translational implications.

BACKGROUND:Neoadjuvant immunotherapy has emerged as a promising strategy for treating esophageal squamous cell carcinoma (ESCC). This study evaluates the therapeutic efficacy and safety of neoadjuvant immunochemotherapy (nICT) in ESCC and explores potential biomarkers associated with treatment outcomes. METHODS:Patients with locally advanced ESCC were enrolled and received two cycles of nICT followed by surgical resection. The primary endpoint was the pathological complete response rate, while secondary endpoints included overall survival (OS), event-free survival (EFS), safety, and the identification of predictive biomarkers. RESULTS:A total of 47 patients were enrolled in the study, with 42 undergoing surgical resection, all of whom achieved R0 resection. The rates of complete and partial pathological responses were 28.5% and 16.7%, respectively. The 1-year and 2-year EFS rates were 82% and 37.3%, while OS rates were 100% and 71.4%, respectively. The majority of treatment-related adverse events were Grade 1-2, and no surgical delays were observed. RNA sequencing analysis identified epithelial-mesenchymal transition as the most significantly enriched pathway in non-responders. Notably, higher infiltration of normal fibroblasts was associated with improved pathological response and enhanced long-term survival, while myofibroblastic cancer-associated fibroblasts (myCAF) negatively impacted treatment efficacy and clinical outcomes. CONCLUSIONS:Neoadjuvant PD-1 inhibitors combined with chemotherapy show promising potential for patients with locally advanced ESCC, inducing a robust immune response that correlates with clinical outcomes. The infiltration of myCAF emerges as a potential predictive biomarker for treatment response and disease progression, underscoring the need for further mechanistic exploration and validation in larger cohorts.

AIMS:Left ventricular (LV) strain derived by three-dimensional (3D) speckle-tracking echocardiography (STE) has been demonstrated to be correlated with myocardial fibrosis (MF). However, whether 3D-STE parameters provided a similar estimation of LV MF compared with two-dimensional (2D) STE indices and late gadolinium enhancement (LGE) of cardiac magnetic resonance (CMR) imaging against histological MF remains unknown. The aim of this study was to determine whether 3D-STE parameters were similar to 2D-STE indices and LGE CMR in assessing LV MF in patients with end-stage heart failure (HF) against histological MF. METHODS:Speckle-tracking echocardiography and CMR were performed in 109 patients with end-stage HF who underwent heart transplantation. Left ventricular global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were obtained from 2D-STE and 3D-STE. The degree of MF was assessed using LGE CMR and Masson's staining of the LV myocardial samples. One hundred nine patients were divided into 3 groups based on the tertiles of histologic MF. RESULTS:Myocardial fibrosis was strongly correlated with 3D-GLS (r = 0.70, P < .001), moderately correlated with LGE extent and 2D-GLS (r = 0.64, r = 0.58; P < .001 for each), and weakly correlated with 3D-GRS, 3D-GCS, 2D-GRS, and 2D-GCS (r = -0.40, r = 0.29, r = -0.38, r = 0.25; P < .01 for each). The correlation of 3D-GLS with LV MF was similar to that of LGE with LV MF (0.70 vs 0.64; P = .427). The correlations of segmental 3D longitudinal strain with regional MF were similar to that of segmental LGE with regional MF for both the ventricular septum and LV lateral wall (r = 0.68 vs 0.57, r = 0.71 vs 0.62, P > .05 for both). The positive and negative predictive values, as well as the area under the curve for identifying severe MF, were comparable among 3D-GLS, 2D-GLS, and LGE. The model with 3D-GLS (R2 = 0.53, P < .001; Akaike information criterion = 413) was similar to that with LGE (R2 = 0.50, P < .001; Akaike information criterion = 418) for reflecting the degree of LV MF. CONCLUSIONS:Three-dimensional GLS can be considered a novel functional parameter that may correlate with the extent of LV MF in patients with end-stage HF, demonstrating accuracy comparable to that of 2D-GLS and LGE CMR in identifying severe MF.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with limited treatment efficacy and frequent resistance to conventional therapies. Recent advances have uncovered the critical influence of the human microbiota—complex communities of bacteria, viruses, fungi, and other microorganisms—on lung cancer pathogenesis and therapeutic responses. This review synthesizes current knowledge on the compositional and functional roles of microbiota across multiple body sites, including the gut, lung, tumor microenvironment, circulation, and oral cavity, highlighting their contributions to tumor initiation, progression, metastasis, and immune regulation. We emphasize the bidirectional communication between microbial metabolites and host immune pathways, particularly the gut–lung axis, which modulates systemic and local antitumor immunity. Importantly, microbiota composition has been linked to differential responses and toxicities in chemotherapy, radiotherapy, targeted therapy, and immune checkpoint blockade. Microbiota-targeted interventions, such as probiotics, fecal microbiota transplantation, and selective antibiotics, show promising potential to enhance treatment efficacy and mitigate adverse effects. However, challenges remain in clinical translation due to interindividual microbiome variability, mechanistic complexities, and limited longitudinal data. Future research integrating multi-omics, microbial functional profiling, and controlled clinical trials is essential to harness the microbiome as a precision medicine tool in lung cancer management. This review provides a comprehensive overview of the emerging role of microbiota in lung cancer development and therapy, offering new perspectives for innovative therapeutic strategies.

ABSTRACT:Research on IgG4-related disease (IgG4-RD), an autoimmune condition recognized to be a unique disease entity only two decades ago, has processed from describing patients' symptoms and signs to summarizing its critical pathological features, and further to investigating key pathogenic mechanisms. Challenges in gaining a better understanding of the disease, however, stem from its relative rarity-potentially attributed to underrecognition-and the absence of ideal experimental animal models. Recently, with the development of various high-throughput techniques, "omics" studies at different levels (particularly the single-cell omics) have shown promise in providing detailed molecular features of IgG4-RD. While, the application of omics approaches in IgG4-RD is still at an early stage. In this paper, we review the current progress of omics research in IgG4-RD and discuss the value of machine learning methods in analyzing the data with high dimensionality.

BACKGROUND:Head and neck squamous cell carcinoma (HNSC) is the seventh most common cancer worldwide. Although there are several options for the treatment of HNSC, there is still a lack of better biomarkers to accurately predict the response to treatment and thus be more able to correctly treat the therapeutic modality.METHODS:First, we typed cases from the TCGA-HNSC cohort into subtypes by a Bayesian non-negative matrix factorization (BayesNMF)-based consensus clustering approach. Subsequently, genomic and proteomic data from HNSC cell lines were integrated to identify biomarkers of response to targeted therapies and immunotherapies. Finally, associations between HNSC subtypes and CD8 T-cell-associated effector molecules, common immune checkpoint genes, were compared to assess the potential of HNSC subtypes as clinically predictive immune checkpoint blockade therapy.RESULTS:The 500 HNSC cases from TCGA were put through a consensus clustering approach to identify six HNSC expression subtypes. In addition, subtypes with unique proteomics and dependency profiles were defined based on HNSC cell line histology and proteomics data. Subtype 4 (S4) exhibits hyperproliferative and hyperimmune properties, and S4-associated cell lines show specific vulnerability to ADAT2, EIF5AL1, and PAK2. PD-L1 and CASP1 inhibitors have therapeutic potential in S4, and we have also demonstrated that S4 is more responsive to immune checkpoint blockade therapy.CONCLUSION:Overall, our HNSC typing approach identified robust tumor-expressing subtypes, and data from multiple screens also revealed subtype-specific biology and vulnerabilities. These HNSC expression subtypes and their biomarkers will help develop more effective therapeutic strategies.

INTRODUCTION:SETD1A is upregulated in non-small cell lung cancer (NSCLC) tissues. This study investigated the molecular mechanism of the SETD1A/WTAPP1/WTAP axis in NSCLC.METHODS:Ferroptosis is a unique cell death mode driven by iron-reliant phospholipid peroxidation, which is regulated by multiple cellular metabolic pathways, including REDOX homeostasis, iron metabolism, mitochondrial activity and metabolism of amino acids, lipids and sugars. Thus, the levels of ferroptosis markers (MDA, SOD, GSH) were measured in vitro, and NSCLC cell behaviors were assessed. SETD1A-mediated H3K4me3 methylation was analyzed. SETD1A-exerted effects on ferroptosis and tumor growth in vivo were verified in nude mouse models.RESULTS:SETD1A was highly expressed in NSCLC cells. Silencing SETD1A suppressed NSCLC cell proliferation and migration, inhibited MDA, and enhanced GPX4, SOD, and GSH levels. SETD1A elevated WTAP expression through WTAPP1 upregulation by mediating H3K4me3 methylation in the WTAPP1 promoter region. WTAPP1 overexpression partly averted the promotional effect of silencing SETD1A on NSCLC cell ferroptosis. WTAP interference abrogated the inhibitory effects of WTAPP1 on NSCLC cell ferroptosis. Silencing SETD1A facilitated ferroptosis and accelerated tumor growth in nude mice through the WTAPP1/WTAP axis.CONCLUSION:SETD1A amplified WTAP expression through WTAPP1 upregulation by mediating H3K4me3 modification in the WTAPP1 promoter region, thus promoting NSCLC cell proliferation and migration and inhibiting ferroptosis.

PURPOSE:There is currently limited information on the utility of transthoracic echocardiography (TTE)-derived Doppler parameters for assessing bioprosthetic tricuspid valve (BTV) dysfunction. Our study aimed to establish the precision and appropriate reference ranges for routinely collected transthoracic Doppler parameters in the assessment of BTV dysfunction. METHODS:We retrospectively evaluated 100 BTV patients who underwent TTE. Based on redo surgical confirmation or more than 2 repeat TTE or transesophageal echocardiography (TEE) examinations, patients were allocated to normal (n = 61), regurgitant (n = 24), or stenotic (n = 15) BTV group. Univariate and multivariate binary logistic regression were performed to identify TTE Doppler parameters that detected BTV dysfunction. RESULTS:The VTI ratio (VTITV/VTILVOT) was the most accurate Doppler parameter for detecting BTV dysfunction, with a ratio of >2.8 showing 84.6% sensitivity and 90.2% specificity. VTI ratio > 3.2, mean gradient (MGTV) > 6.2 mmHg and pressure half-time > 218 ms detected significant BTV stenosis, with sensitivities of 100%, 93.3% and 93.3% and specificities of 82.4%, 75.3% and 87.1%, respectively. After multivariate analysis, the VTI ratio > 2.8 (OR = 9.00, 95% CI = 2.13-41.61, p = .003) and MGTV > 5.1 mmHg (OR = 6.50, 95% CI = 1.69-27.78, p = .008) were the independent associations of BTV dysfunction. With these cutoff values, 75.0%-92.2% of normal and 62.5%-96.0% of dysfunctional BTV were identified. CONCLUSIONS:Doppler parameters from TTE can accurately identify BTV dysfunction, particularly with VTI ratio > 2.8 and MGTV > 5.1 mmHg, to assess the need for additional testing with TEE.

Background and aimsTranscatheter tricuspid valve replacement (TTVR) has recently emerged as a novel therapeutic approach for managing severe tricuspid regurgitation (TR). However, surgical tricuspid valve replacement (STVR) continues to be the predominant treatment modality. There are limited comparative data on both procedures. This study aimed to compare clinical and echocardiographic outcomes between patients who underwent mini-thoracotomy transatrial LuX-Valve TTVR and those who underwent STVR.MethodsThis study prospectively collected patients with severe TR who underwent TTVR (n = 29) or isolated STVR (n = 59) at Wuhan Union Hospital from 2019 to 2022. All TTVR patients received the LuX-Valve via a mini-thoracotomy and transatrial approach. The clinical and echocardiographic outcomes were compared at 30-day and one-year follow-ups.ResultsAt baseline, patients with LuX-Valve TTVR had higher surgical risk scores and a greater proportion of right ventricular dysfunction compared with STVR. In the early postoperative period, the STVR group had a greater decrease in right ventricular function. Hospital length of stay (LOS), intensive care unit LOS, total procedure time, and tracheal intubation time were shorter in the TTVR than in the STVR group. The incidence of postoperative paravalvular leaks was higher among patients who underwent TTVR. Compared to the STVR group, the pacemaker implantation rate was lower in the TTVR group. During follow-up, the peak tricuspid valve velocity and mean gradient in the TTVR group were consistently lower than those in the STVR group. There was similar mortality between TTVR and STVR at 30-day and one-year follow-ups.ConclusionsThe mini-thoracotomy transatria LuX-Valve TTVR has a higher incidence of paravalvular leaks and a lower rate of pacemaker implantation than STVR, with similar 30-day and one-year mortality rates. In some respects, mini-thoracotomy transatrial LuX-Valve TTVR may be a feasible and safe treatment option for specific populations, or it could potentially serve as an alternative therapy to supplement conventional STVR. Further follow-up is required to assess differences in long-term clinical outcomes and valve durability.

Immune checkpoint inhibitor (ICI) treatment has the potential to induce durable disease remission. However, the current combined positive score (CPS) is insufficient accurate for predicting which patients will benefit from it. In the present study, a real-world retrospective study was conducted on 56 patients of HNSCC who received ICI treatment. Then the treatment that patient received and levels of pre-treatment blood inflammatory markers (NLR, MLR and PLR) were identified to develop a model for predicting immunotherapy response. Notably, the model achieved an area under the curve (AUC) of 0.877 (95 % CI 0.769-0.985) , providing a larger net benefit than the CPS marker (AUC=0.614, 95 % CI 0.466-0.762). Furthermore, the internal validation of the prediction model showed a C-index of 0.835. Patients with high score of the model would get improved PFS than those with low score. Therefore, the prediction model for patients with local advanced or R/M HNSCC receiving ICI treatment, which represented an better efficient prediction of immunotherapy response than CPS marker.