Journal of Immunotherapy最新文献

{"title":"DLGAP5 Drives Lung Cancer Progression: Combined Bioinformatics and Clinical Prognostic Analysis.","authors":"Min She, Chang Li, Fuxiang Li","doi":"10.1097/CJI.0000000000000597","DOIUrl":"10.1097/CJI.0000000000000597","url":null,"abstract":"<p><p>DLGAP5 has emerged as a potential biomarker implicated in tumor progression across various cancers, yet its prognostic value in lung cancer remains to be fully elucidated. In this study, we integrated comprehensive bioinformatics analyses with clinical data to investigate the expression patterns of DLGAP5 and its association with patient outcomes in lung cancer. Expression profiling revealed that DLGAP5 levels varied modestly across clinical subgroups defined by age, sex, tumor stage, and grade, with no statistically significant differences observed. Survival analyses demonstrated that elevated DLGAP5 expression was significantly correlated with reduced overall survival, while disease-free survival showed no marked difference. Multivariate Cox regression and clinical prognostic models further confirmed DLGAP5 as an independent risk factor associated with poorer prognosis (HR=2.35, 95% CI: 1.10-5.03, P =0.021). Functional enrichment analyses of differentially expressed genes between the low-DLGAP5 expression group and high-DLGAP5 expression group identified key biological processes and pathways, including transcriptional regulation and cytoskeletal organization, potentially mediating DLGAP5's role in lung cancer progression. These findings provide robust evidence supporting the prognostic relevance of DLGAP5 in lung cancer and underscore its potential utility as a therapeutic target.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"183-191"},"PeriodicalIF":2.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of 2 Ubiquitin-Proteasome System-Related Subtypes in Esophageal Squamous Cell Carcinoma for Prognostic and Immunotherapeutic Response Prediction.","authors":"Chao Jiang, Meng Shen, Jing Zhu, Xiu Zhang, Kai Chen","doi":"10.1097/CJI.0000000000000587","DOIUrl":"10.1097/CJI.0000000000000587","url":null,"abstract":"<p><strong>Summary: </strong>Ubiquitin-proteasome system (UPS) is implicated in pathogenesis and progression of esophageal squamous cell carcinoma (ESCC), representing a promising therapeutic target. However, clinical significance of UPS in ESCC remains incompletely elucidated. UPS genes associated with ESCC survival were first screened through univariate Cox regression analysis. Consensus clustering was performed on TCGA-ESCC cohort based on these genes. Functional enrichment, tumor immune microenvironment analysis, and somatic mutation profiling were conducted for different clusters. Potential therapeutics and biomarkers were evaluated, and miRNA-TF-hub gene regulatory network was constructed. ESCC samples were stratified into 2 distinct clusters (cluster 1 and cluster 2), with cluster 1 demonstrating superior overall survival. Differential analysis revealed enrichment in cell adhesion and calcium signaling pathways. Immune infiltration analysis indicated elevated CD8+ T cells, mast cells, neutrophils, and TILs in cluster 2, alongside lower TIDE scores. TP53 exhibited the highest mutation frequency (93% vs. 86% in cluster 1 vs. cluster 2). Selumetinib, entinostat, and erlotinib were identified as candidate drugs for cluster 2, whereas tozasertib, alpelisib, and cediranib showed higher suitability for cluster 1. Ten potential biomarkers, 13 transcription factors, and 2 miRNAs were characterized. This study elucidates the role of UPS in ESCC progression and provides a framework for personalized treatment strategies.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"192-201"},"PeriodicalIF":2.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sugemalimab for Post-PD-1 Progression in Non-small Cell Lung Cancer.","authors":"Li Xu, Xingxiang Pu, Qianzhi Wang, Liyu Liu, Yi Kong, Kang Li, Yan Xu, Jia Li, Fang Xu, Shuzhi Liang, Lin Wu, Bolin Chen","doi":"10.1097/CJI.0000000000000602","DOIUrl":"10.1097/CJI.0000000000000602","url":null,"abstract":"<p><p>This single-center, retrospective real-world study investigated the effectiveness and safety of sugemalimab-based rechallenge in patients with advanced non-small cell lung cancer who experienced disease progression after prior programmed cell death protein 1 (PD-1) inhibitor therapy. Eligible patients had previously achieved clinical benefit (progression-free survival [PFS] ≥6 mo), an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and no actionable driver alterations. Nineteen patients received sugemalimab every 3 weeks as monotherapy or in combination with chemotherapy and/or antiangiogenic agents. The objective response rate was 26.3% (5/19; 95% CI: 9.1-51.2), and the disease control rate was 89.5% (17/19; 95% CI: 66.9-98.7), with a median PFS of 4.4 months. Higher programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) correlated with prolonged PFS (TPS ≥50% vs. TPS <1%: 6.1 vs. 2.8 mo; hazard ratio (HR) 0.4, 95% CI: 0.1-0.8). Hypothyroidism was the most common treatment-related adverse event, while grade 3/4 events were uncommon. These findings indicate measurable activity of sugemalimab-based rechallenge in a pre-enriched population and support prospective validation with biomarker-informed stratification.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"202-208"},"PeriodicalIF":2.9,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Molecular Subtypes and a Novel Prognostic Model for Lung Squamous Cell Carcinoma Based on Adenylate Uridylate (AU)-Rich Element Genes.","authors":"Junchao Huang, Siyang Chen, Yakun Liu","doi":"10.1097/CJI.0000000000000580","DOIUrl":"10.1097/CJI.0000000000000580","url":null,"abstract":"<p><p>Adenylate uridylate-rich element genes (AREGs) are crucial in modulating gene expression following transcription. However, the comprehensive role of AREGs in lung squamous carcinoma (LUSC) r emains inadequately understood. Transcriptome data from TCGA and GTEx databases to identify differentially expressed AREGs. Clustering algorithms were used to identify AREGs-related subtypes, and a prognostic model was developed through univariate/multivariate and LASSO regression analyses. Following this, we created a nomogram integrating clinical pathologic characteristics and the risk model. The immune microenvironment was evaluated using CIBERSORT, ESTIMATE, and MCPcounter analyses. We examined the mRNA expression of the signature genes in normal and lung squamous carcinoma cells using RT-qPCR. Finally, we assessed the sensitivity to drugs based on the signature genes in risk patients. Patients with the 2 identified molecular subtypes exhibit distinct prognoses and immune microenvironments. We identified 5 genes with prognostic significance that can serve as independent predictors in clinical practice. The low-risk patients demonstrates more favorable prognostic outcomes, while the high-risk patients show elevated immune scores and increased immune cell infiltration, suggesting a favorable response to immunotherapy. RT-qPCR results showed upregulation of FAM83A and TINAGL1 and downregulation of FGG and ADH1C in LUSC. In addition, the low-risk patients show increased sensitivity to vinorelbine. The molecular subtypes and prognostic model based on AREGs demonstrate reliable clinical prognostic value. This finding may contribute to personalized and precise treatment for patients with LUSC, offering new insights for improving patient outcomes.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"137-151"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145124927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Life-Threatening Radiation Necrosis After Complete Response to Pembrolizumab in a Patient With a Metastatic Silent PIT1 Pituitary Neuroendocrine Tumor (PitNET).","authors":"Dario De Alcubierre, Tiziana Feola, Francesca Gianno, Monica Verrico, Francesca Carbonara, Eugenio Venditti, Andrea M Isidori, Vincenzo Esposito, Giuseppe Minniti, Marie-Lise Jaffrain-Rea","doi":"10.1097/CJI.0000000000000601","DOIUrl":"10.1097/CJI.0000000000000601","url":null,"abstract":"<p><p>Metastatic pituitary neuroendocrine tumors (metPitNETs) are rare neoplasms with limited therapeutic options. Temozolomide is the first-line therapy, but primary or secondary resistance frequently occurs. Immune checkpoint inhibitors (ICIs) are emerging as a promising second-line option; however, clinical experience remains limited. We report the long-term follow-up of a 62-year-old male patient who received pembrolizumab (PBZ) treatment for a silent metPitNET derived from the PIT1 lineage after multiple surgical and radiation therapies and temozolomide failure. PBZ was proposed based on extensive PD-L1 expression by tumor cells. A remarkable clinical, radiologic, and metabolic response was soon observed, progressively leading to complete disease remission after 21 months of treatment, with moderate immune-related adverse events. However, an unexpected rapid neurological deterioration occurred, due to the progression of a pseudotumoral temporal radionecrosis surrounded by an impressive vasogenic oedema, requiring emergency neurosurgery 7 weeks after PBZ withdrawal. The temporal mass had progressively developed on a previous small temporal metastasis treated through stereotactic radiosurgery, the corresponding area was hypometabolic at 18 FDG PET-CT imaging, and histopathologic examination confirmed extensive radionecrosis and the absence of residual tumor cells. This is the first documented complete response to ICI in a PIT1-derived metPitNET. However, this remarkable response was complicated by the severe evolution of a brain radionecrosis, probably favoured by long-term PBZ. This case underscores the need for multidisciplinary expertise to differentiate treatment effects from neoplastic progression and to carefully follow-up the patients for potentially severe late treatment-related complications. It also questions the optimal duration of treatment in responsive cases.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"178-182"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13061375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147271152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic and Epitranscriptomic Modulation by STAT1: Unraveling T Helper Cell Differentiation in NSCLC.","authors":"Roshni Bibi, Melvin George, Koustav Sarkar","doi":"10.1097/CJI.0000000000000582","DOIUrl":"10.1097/CJI.0000000000000582","url":null,"abstract":"<p><strong>Abstract: </strong>The lack of targetable mutations in 50% of NSCLC cases and resistance to therapies underscore the need for alternative treatments, with epigenetic strategies potentially regulating tumor suppressor genes to inhibit growth. Our focus is to understand the STAT1-mediated epigenetic and epitranscriptomic modulations, such as R-loop formation, histone methylation/demethylation, histone acetylation and deacetylation, DNA methylation, and m6A RNA methylation, in T helper cell (TH) differentiation to evoke tumor-protective immune responses in non-small cell lung cancer (NSCLC) by knocking out (KO) and overexpressing (OE) STAT1. Peripheral blood mononuclear cells (PBMCs) were isolated from NSCLC patients and healthy controls using Ficoll-Hypaque density-gradient centrifugation. CD4+ T cells were purified with magnetic activated cell sorting (MACS). Subsequently, CRISPR/Cas9 knock-out and overexpression techniques were applied, followed by qRT-PCR to evaluate 5-mC, m6A RNA methylation, gene expression, and transcription factor enrichment. Mutations in STAT1 can cause severe immunodeficiency and malignancy, linked to genomic instability from R-loops-DNA-RNA hybrids that lead to DNA breaks through transcription-coupled nucleotide excision repair. Our study examines epigenetic regulators in CD4+ T helper cells from NSCLC patients, focusing on the effects of STAT1 depletion and overexpression on R-loop formation at key gene loci specific to T helper cells. Depletion of STAT1 increased R-loop frequencies, DNA methylation, histone deacetylation, and histone methylation, whereas its overexpression decreased them. Abnormal epitranscriptomic alterations, including m 6 A RNA methylation, were observed, indicating that STAT1 is crucial for T helper cell differentiation and immune responses in NSCLC, presenting promising avenues for targeted therapeutic interventions.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"152-163"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145286278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival Benefit of Immunotherapy in Patients With Stage IV Microsatellite Stable Rectal Cancer: A Propensity-Score Matched Analysis.","authors":"Sameh Hany Emile, Nir Horesh, Zoe Garoufalia, Anjelli Wignakumar, Ebram Salama, Steven D Wexner","doi":"10.1097/CJI.0000000000000600","DOIUrl":"10.1097/CJI.0000000000000600","url":null,"abstract":"<p><p>This study aimed to assess factors associated with overall survival (OS) in patients with microsatellite stable (MSS) stage IV rectal cancer treated with immunotherapy. In this retrospective review of the NCDB (2015-2021), patients with MSS stage IV rectal adenocarcinoma were divided into immunotherapy and control groups, and propensity-score matched and compared. Multivariable Cox regression analysis was performed to assess the effect of immunotherapy and KRAS genotype on OS. Of 6489 included patients (64.6% males), immunotherapy was given to 47.9%. After matching for age, insurance type, liver metastases, surgery, radiation therapy, and chemotherapy, there were 2422 patients in each group. In the matched cohort, immunotherapy was associated with a similar median OS to the control group [31.8 (95% CI: 27.8-32.2) months vs 29.7 (95% CI: 27.8-32.2) months, P = 0.062]. Immunotherapy was not independently associated with improved OS (HR: 0.88, 95% CI: 0.69-1.14, P = 0.341) but was associated with longer median OS in black patients (25.8 vs 19.1 mo, P = 0.019), patients with bone metastases (22.1 vs 10.7, P < 0.001) and with KRAS mutation (27.4 vs 24.3 mo, P = 0.003). There was no survival benefit from immunotherapy when combined with radical resection, radiation therapy, or chemotherapy. In conclusion, immunotherapy was associated with a modest increase in OS of MSS stage IV rectal cancers, but not independently associated with improved survival. Black patients with bone metastases and KRAS mutations may have survival benefit from immunotherapy. Increased OS with immunotherapy was noted only in patients who did not have surgery, radiation, or chemotherapy. These results seem somewhat disappointing given the enthusiasm for immunotherapy.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"164-172"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146142433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brief Communication: Severe Immuno-Induced Rhinosinusitis With Deafness After Ipilimumab and Nivolumab Combination for Melanoma, and Review of the Literature.","authors":"Maëva Boyer, Mélodie Kerimian, Alix Ribadeau Dumas, Skander Korbi, Caroline Dutriaux, Margot Bouquerel, Marie Guicheney, Sorilla Prey","doi":"10.1097/CJI.0000000000000592","DOIUrl":"10.1097/CJI.0000000000000592","url":null,"abstract":"<p><p>Immunotherapy with immune checkpoint inhibitors (ICI) is widely used to treat cancers, and reports of rare immune-related adverse events (irAEs) are increasing. Ear, nose, and throat (ENT) irAEs are often underestimated, as patients rarely report rhinorrhea and most cases of sinusitis are asymptomatic, detected only during tumor CT assessments. We report a rare case of severe rhinosinusitis with hearing loss after ipilimumab and nivolumab combination therapy for melanoma. Due to steroid dependency, the patient was successfully treated with intravenous infliximab but was left with residual deafness. Physicians should be aware of these potentially serious ENT complications, which can affect quality of life, to allow timely referral to an ENT specialist. In severe cases, multidisciplinary care is needed to consider steroid-sparing treatments such as infliximab.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"173-177"},"PeriodicalIF":2.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145809841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy-Associated Autoimmune Hemolytic Anemia: Two Case Reports and a Literature Review.","authors":"Mariana C Gouveia, Yumi R Shinkado, Ana Z L Pereira, João H L Feldmann, Erick M Xavier, Rodrigo R Munhoz, Mariana Scaranti","doi":"10.1097/CJI.0000000000000606","DOIUrl":"10.1097/CJI.0000000000000606","url":null,"abstract":"<p><p>The advent of immune checkpoint inhibitors (ICIs) has transformed the treatment landscape of various malignancies. While these therapies have demonstrated significant efficacy, they are often accompanied by immune-related adverse events (irAEs). Among these, hematologic immune-related toxicities are notably rare. Here, we describe 2 cases of immunotherapy-associated autoimmune hemolytic anemia (ir-AIHA) following the use of programmed cell death 1 (PD-1) ICIs in patients with locally advanced melanoma and cervical cancer. With the increasing use of ICIs, it is essential for physicians to maintain a high index of clinical suspicion for this rare but serious irAE, ensuring timely diagnosis and effective management to optimize patient outcomes.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: NUSAP1 Promotes Immunity and Apoptosis by the SHCBP1/JAK2/STAT3 Phosphorylation Pathway to Induce Dendritic Cell Generation in Hepatocellular Carcinoma.","authors":"Guojie Chen, WenYa Li, Ruomu Ge, Ting Guo, Yuhan Zhang, Chenglin Zhou, Mei Lin","doi":"10.1097/CJI.0000000000000599","DOIUrl":"10.1097/CJI.0000000000000599","url":null,"abstract":"","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":"49 3","pages":"135"},"PeriodicalIF":2.9,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147443567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}