Journal of Immunotherapy最新文献

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Association Between Metformin Use and Mortality Among Individuals With Non-Small Cell Lung Cancer Receiving Immune Checkpoint Inhibitors: A Retrospective Cohort Study. 接受免疫检查点抑制剂的非小细胞肺癌患者使用二甲双胍与死亡率之间的关系:一项回顾性队列研究
IF 2.9 4区 医学
Journal of Immunotherapy Pub Date : 2025-09-01 DOI: 10.1097/CJI.0000000000000565
Xinyi Sun, James Heyward, Joseph C Murray, G Caleb Alexander, Hemalkumar B Mehta
{"title":"Association Between Metformin Use and Mortality Among Individuals With Non-Small Cell Lung Cancer Receiving Immune Checkpoint Inhibitors: A Retrospective Cohort Study.","authors":"Xinyi Sun, James Heyward, Joseph C Murray, G Caleb Alexander, Hemalkumar B Mehta","doi":"10.1097/CJI.0000000000000565","DOIUrl":"10.1097/CJI.0000000000000565","url":null,"abstract":"<p><p>Metformin has the potential to synergistically enhance the effect of immune checkpoint inhibitors (ICI) in nonsmall cell lung cancer (NSCLC). We evaluated the association between metformin use before ICI initiation and cancer-specific and all-cause mortality among NSCLC patients. We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare data (2013-2019), including NSCLC patients with type 2 diabetes who newly initiated ICI therapy and had prior antidiabetic medication use. The exposure was metformin monotherapy versus sulfonylurea and/or dipeptidyl peptidase-4 (DPP-4) inhibitors. The primary outcome was cancer-specific mortality, and the secondary outcome was all-cause mortality. We used stabilized inverse probability of treatment weighting (sIPTW) to adjust for confounders. Fine-Gray competing risk model estimated cancer-specific mortality, while Cox proportional hazards model evaluated all-cause mortality. We included 1123 metformin users and 362 sulfonylurea/DPP-4 users. Although baseline characteristics differed, groups were well balanced after weighting. The adjusted incidence rate (aIR) of cancer-specific mortality was 82 versus 81 (aIR difference=1, 95% CI: -13 to 16), and all-cause mortality was 71 versus 67 (aIR difference=4, 95% CI: -6 to 15) per 100 person-years for metformin and sulfonylurea/DPP-4 users, respectively. Metformin use was not significantly associated with cancer-specific mortality (adjusted hazard ratio (aHR)=1.08, 95% CI: 0.88-1.33) and all-cause mortality (aHR=1.07, 95% CI: 0.90-1.26). In this large, diverse cohort of individuals with NSCLC using ICI, there was no statistically significant association between metformin use and cancer-specific or all-cause mortality.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"273-280"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144475599","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}
引用次数: 0
Investigating Overlapping Immune-related Genetic Markers in Cholangiocarcinoma and Inflammatory Bowel Disease for Predictive Prognosis. 研究胆管癌和炎症性肠病中重叠免疫相关遗传标记的预测预后
IF 2.9 4区 医学
Journal of Immunotherapy Pub Date : 2025-09-01 DOI: 10.1097/CJI.0000000000000562
Shuang Zheng, Caizheng Wang, Junhui Fu, Jinfan Shao
{"title":"Investigating Overlapping Immune-related Genetic Markers in Cholangiocarcinoma and Inflammatory Bowel Disease for Predictive Prognosis.","authors":"Shuang Zheng, Caizheng Wang, Junhui Fu, Jinfan Shao","doi":"10.1097/CJI.0000000000000562","DOIUrl":"10.1097/CJI.0000000000000562","url":null,"abstract":"<p><p>This study aims to explore the common immune-related gene characteristics of cholangiocarcinoma (CHOL) and inflammatory bowel disease (IBD) to predict disease prognosis. By analyzing the gene expression data from the TCGA, GEO, and NGDC databases, differentially expressed immune-related genes (DE-IRGs) were screened, and a prognostic model was constructed. The results showed that CCR7, OSM, S100P, ACVR1C, OSMR, SPP1, and PIK3R3 were key immune-related genes, and their expressions were closely related to the occurrence and development of CHOL and IBD. Patients in the low immune risk score (IRS) group had more abundant antitumor immune cell infiltration, while those in the high IRS group had more macrophage infiltration. In addition, the model based on these genes had good predictive ability for the diagnosis and prognosis of CHOL and IBD, with an area under the ROC curve (AUC) value exceeding 0.7. This study also predicted potential small molecule drugs that might be effective for the treatment of CHOL, such as Umbralisib and Tamoxifen. In conclusion, this study provides new biomarkers and potential targets for diagnosis, prognosis assessment, and treatment of CHOL and IBD.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"258-272"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094024","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}
引用次数: 0
CSF1-CAR Specifically Targets CSF1R + Pancreatic Cancer Cells and Tumor-Associated Macrophages. CSF1-CAR特异性靶向CSF1R+胰腺癌细胞和肿瘤相关巨噬细胞
IF 2.9 4区 医学
Journal of Immunotherapy Pub Date : 2025-09-01 DOI: 10.1097/CJI.0000000000000563
Yongjie Zhu, Ruipu Sun, Jiawei Fan, Haiyan Ma, Bin Sun
{"title":"CSF1-CAR Specifically Targets CSF1R + Pancreatic Cancer Cells and Tumor-Associated Macrophages.","authors":"Yongjie Zhu, Ruipu Sun, Jiawei Fan, Haiyan Ma, Bin Sun","doi":"10.1097/CJI.0000000000000563","DOIUrl":"10.1097/CJI.0000000000000563","url":null,"abstract":"<p><strong>Abstract: </strong>A highly suppressive tumor immune microenvironment and nonspecific target endow malignant tumors with CAR-T cells. CSF1R is highly expressed on pancreatic cancer tissues compares with normal tissues in GEPIA database and M2 macrophages mainly contributing to the suppressive tumor microenvironment (TME), suggesting that CSF1R is a suitable antigen. CSF1 is the natural ligand of CSF1R, so we constructed a CSF1-CAR and tested its cytotoxic effect on tumor cells and macrophages in vitro. Our results demonstrated that CSF1-CAR-T cells can lyse tumor cells dependent on CSF1R expression. Meanwhile, CSF1-CAR-T also lyse CSF1R + M2 macrophages, suggesting that CSF1-CAR-T cells play a role in eliminating tumor cells and remodeling the TME.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"237-243"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078495","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}
引用次数: 0
Harnessing Calmodulin-Related Genes to Build a Prognostic Model in Esophageal Squamous Cell Carcinoma for a Comprehensive Analysis of Single-Cell Immune Characteristics and Drug Efficacy. 利用钙调素相关基因构建食管鳞状细胞癌预后模型,综合分析单细胞免疫特性和药物疗效。
IF 2.9 4区 医学
Journal of Immunotherapy Pub Date : 2025-09-01 DOI: 10.1097/CJI.0000000000000561
Shasha Cao, Shumin Lun, Lijuan Duan, Zhaowei Gao, Xiaoxiao Wang, Yutong Li, Yaowen Zhang
{"title":"Harnessing Calmodulin-Related Genes to Build a Prognostic Model in Esophageal Squamous Cell Carcinoma for a Comprehensive Analysis of Single-Cell Immune Characteristics and Drug Efficacy.","authors":"Shasha Cao, Shumin Lun, Lijuan Duan, Zhaowei Gao, Xiaoxiao Wang, Yutong Li, Yaowen Zhang","doi":"10.1097/CJI.0000000000000561","DOIUrl":"10.1097/CJI.0000000000000561","url":null,"abstract":"<p><p>Calmodulin (CALM) has a bearing on the prognosis of various cancers. However, the prognostic value of CALM in esophageal squamous cell carcinoma (ESCC) remains unelucidated. Differentially expressed genes (DEGs) were screened between normal and tumor groups of TCGA-ESCC sets. The intersection of DEGs with calmodulin-related genes (CRGs) yielded differentially expressed CRGs (DE-CRGs). A prognostic model was established using LASSO Cox regression analysis and multivariate Cox regression analysis. qPCR validated the expression of prognostic feature genes. Analysis of gene expression patterns of different cellular clusters was based on single-cell sequencing data. Lastly, GSEA enrichment, immune infiltration, mutational profiling, drug sensitivity, and molecular docking as well as cellular thermal shift assay (CETSA) were conducted for ESCC patients. A prognosis model with excellent predictive capability was created based on 4 feature genes (ATP2B3, CALB1, KCNQ1, and MYO1G). The qPCR results demonstrated that ATP2B3 and KCNQ1 were significantly downregulated in human ESCC cells, whereas CALB1 and MYO1G were upregulated ( P <0.05). Single-cell analysis uncovered that MYO1G and KCNQ1 were mainly expressed in different cell clusters. Furthermore, this risk model was strongly associated with functional pathway enrichment, immune cell infiltration, and somatic mutations. We also identified AZD-8055 may be potential therapy for ESCC patients. The CETSA experiment demonstrated the existence of a favorable binding thermal stability between AZD-8055 and MYO1G. This research may identify potential biomarkers for predicting the prognosis of ESCC patients.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"244-257"},"PeriodicalIF":2.9,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078544","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}
引用次数: 0
Dual Roles of EZH2 in Tumor Proliferation and Immune Evasion in Lung Squamous Cell Carcinoma: A Pathway to Novel Immunotherapeutic Approaches. EZH2在肺鳞状细胞癌的肿瘤增殖和免疫逃避中的双重作用:一种新的免疫治疗途径
IF 2.9 4区 医学
Journal of Immunotherapy Pub Date : 2025-07-01 Epub Date: 2025-06-04 DOI: 10.1097/CJI.0000000000000560
Ling Xu, Chun Ye, Shuihong Yu
{"title":"Dual Roles of EZH2 in Tumor Proliferation and Immune Evasion in Lung Squamous Cell Carcinoma: A Pathway to Novel Immunotherapeutic Approaches.","authors":"Ling Xu, Chun Ye, Shuihong Yu","doi":"10.1097/CJI.0000000000000560","DOIUrl":"10.1097/CJI.0000000000000560","url":null,"abstract":"<p><strong>Abstract: </strong>Lung squamous cell carcinoma (LUSC) remains a major clinical challenge due to its aggressive nature and poor prognosis. Enhancer of zeste homolog 2 (EZH2), a key epigenetic regulator within the polycomb repressive complex 2 (PRC2), has emerged as a critical player in cancer progression. This study investigates the dual role of EZH2 in driving tumor proliferation and modulating the immune microenvironment in LUSC. Bioinformatics analysis revealed significant upregulation of EZH2 in LUSC tissues compared with normal counterparts, with high EZH2 expression correlating with improved overall survival in early-stage patients. Functional assays in EZH2 knockout LUSC cell lines demonstrated reduced tumor cell proliferation, migration, and invasion alongside enhanced apoptosis and cell cycle arrest. Furthermore, in vivo studies using an EZH2 knockout mouse model showed decreased tumor growth and increased immune cell infiltration, including CD8+ T cells, macrophages, and neutrophils. These findings highlight the pivotal role of EZH2 in promoting tumor progression and orchestrating immune evasion mechanisms in LUSC. Given its multifaceted influence on tumor biology and the immune landscape, EZH2 represents a promising therapeutic target for improving outcomes in LUSC patients. Future studies should explore the therapeutic potential of targeting EZH2 to enhance immune responses and overcome resistance to current treatments.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":"48 6","pages":"221-230"},"PeriodicalIF":2.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216047","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}
引用次数: 0
Integrative Multi-Omics Analysis Reveals Molecular Subtypes of Ovarian Cancer and Constructs Prognostic Models. 综合多组学分析揭示卵巢癌分子亚型并构建预后模型。
IF 2.9 4区 医学
Journal of Immunotherapy Pub Date : 2025-07-01 Epub Date: 2025-04-09 DOI: 10.1097/CJI.0000000000000557
Min Zhou, Jie Pi, Yuzi Zhao
{"title":"Integrative Multi-Omics Analysis Reveals Molecular Subtypes of Ovarian Cancer and Constructs Prognostic Models.","authors":"Min Zhou, Jie Pi, Yuzi Zhao","doi":"10.1097/CJI.0000000000000557","DOIUrl":"10.1097/CJI.0000000000000557","url":null,"abstract":"<p><strong>Abstract: </strong>Ovarian cancer (OV) remains the most lethal gynecological malignancy. The aim of this study was to identify molecular subtypes of OV through integrative multi-omics analysis and construct machine learning-based prognostic models for predicting the efficacy of immunotherapy. In here, the mutation, copy number variation, RNA sequencing expression profiles, and clinical information were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Multi-omics data were stratified using the MOVICS package, identifying different molecular subtypes. Our analysis identified 2 molecular subtypes (CS1 and CS2) with significant survival differences. Transcriptional regulatory network analysis revealed differential activation of transcription factors such as FOXA1 and GATA3 in CS1, whereas AR and ESR2 were enriched in CS2. A robust prognostic signature comprising 5 key genes was developed through the integration of 10 machine learning algorithms, demonstrating high predictive power across data sets. Immune cell infiltration analysis revealed that anti-tumor immune cells were more abundant in low-risk groups, whereas pro-tumor immune cells predominated in high-risk groups. Furthermore, low-risk patients exhibited better immunotherapy responses and higher tumor mutational burden (TMB). In conclusion, our findings underscore the potential of multi-omics integration in unveiling novel OV subtypes and constructing predictive models that inform personalized treatment strategies. Future research should focus on validating these findings in larger cohorts to enhance OV management through targeted therapeutic approaches.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"197-208"},"PeriodicalIF":2.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811550","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}
引用次数: 0
Effects of Antibiotics on First-line Immunotherapy in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma. 抗生素对鼻咽癌复发或转移患者一线免疫治疗的影响。
IF 3.2 4区 医学
Journal of Immunotherapy Pub Date : 2025-07-01 Epub Date: 2025-04-10 DOI: 10.1097/CJI.0000000000000556
Yuting Fang, Binhao Wu, Rong Zhang, Xiaozhong Chen, Feng Jiang, Qifeng Jin, Ting Jin, Shuang Huang, Changjuan Tao, Mengyun Qiang, Yongfeng Piao, Yonghong Hua, Xinglai Feng, Caineng Cao
{"title":"Effects of Antibiotics on First-line Immunotherapy in Patients With Recurrent or Metastatic Nasopharyngeal Carcinoma.","authors":"Yuting Fang, Binhao Wu, Rong Zhang, Xiaozhong Chen, Feng Jiang, Qifeng Jin, Ting Jin, Shuang Huang, Changjuan Tao, Mengyun Qiang, Yongfeng Piao, Yonghong Hua, Xinglai Feng, Caineng Cao","doi":"10.1097/CJI.0000000000000556","DOIUrl":"10.1097/CJI.0000000000000556","url":null,"abstract":"<p><p>Immunotherapy combined with chemotherapy has become the first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). However, the impact of antibiotic (ATB) use on the efficacy of immunotherapy in RM-NPC remains unclear. A total of 200 patients with RM-NPC who started first-line immunotherapy between October 2021 and September 2023 were included. Forty-six patients received ATB within 60 days before and 42 days after the first infusion of immunotherapy (group ATB+), and the remaining 154 patients were in group ATB-. The median progression-free survival (PFS) times of the ATB+ and ATB- groups were 11.20 and 19.87 months, respectively ( P = 0.061). The 2-year overall survival (OS) rates of the ATB+ and ATB- groups were 52.6% and 76.7%, respectively ( P = 0.001). In multivariate analysis, ATB use was significantly associated with worse OS (hazard ratio = 2.549, P = 0.002). No significant differences were observed between the 2 groups in terms of grade 3+ treatment-related adverse events. ATB use in RM-NPC may reduce the effectiveness of first-line immunotherapy.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"231-236"},"PeriodicalIF":3.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144011811","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}
引用次数: 0
Identification of Immune Characteristics of 2 Subtypes of Breast Cancer by Combining Polyamine Metabolism-related Genes to Help With Immunotherapy. 联合多胺代谢相关基因帮助免疫治疗鉴定2种亚型乳腺癌的免疫特性
IF 2.9 4区 医学
Journal of Immunotherapy Pub Date : 2025-07-01 Epub Date: 2025-04-30 DOI: 10.1097/CJI.0000000000000559
Xiuwen Yi, Bin Tang, Qinghua Mo, Yulan Tang, Wei Fu, Lingling Zhang, Liming Xie
{"title":"Identification of Immune Characteristics of 2 Subtypes of Breast Cancer by Combining Polyamine Metabolism-related Genes to Help With Immunotherapy.","authors":"Xiuwen Yi, Bin Tang, Qinghua Mo, Yulan Tang, Wei Fu, Lingling Zhang, Liming Xie","doi":"10.1097/CJI.0000000000000559","DOIUrl":"10.1097/CJI.0000000000000559","url":null,"abstract":"<p><p>This project aims to explore the clustering value of polyamine metabolism-related genes (PMRGs) in breast cancer (BC) to assist treatment. ConsensusClusterPlus R package was employed to cluster BC patients based on the expression of PMRGs. Using the edgeR R package, we analyzed differentially expressed genes (DEGs) of different molecular clusters. Core genes were screened and enriched by the PPI network. Univariate COX was applied to determine genes tightly linked with survival. ConsensusClusterPlus R package was employed to cluster PMRGs. Differences in immune infiltration and expression of immune checkpoints between 2 subgroups were analyzed. Response to immunotherapy was assessed based on the expression level of immunophenoscore (IPS). Drug sensitivity of different PMRG clusters was assessed by pRRophitic R package. We clustered BC patients into 2 different subtypes with different survival rates and biological functions based on the expression of 16 PMRGs. Application of univariate COX analysis identified genes greatly associated with survival and divided BC patients into 2 different PMRG clusters. Patients in the 2 clusters exhibited differences in overall survival rate and immune cell infiltration levels, with multiple immune cells displaying higher immune levels in PMRG cluster 2. PMRG cluster 2 demonstrated higher expression of HLA and IC as well as IPS. Cluster 1 exhibited higher sensitivity to (5Z)-7-Oxozeaenol, 5-Fluorouracil, and 681640, while cluster 2 exhibited higher sensitivity to A-443654 and A-770041. We identified 2 clusters of PMRG with significant differences in the immune microenvironment in BC and predicted potential drugs, aiming to find new directions for clinical treatment of BC.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"209-220"},"PeriodicalIF":2.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144004130","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}
引用次数: 0
Immune Profiling of Uveal Melanoma Liver Metastases and Response to Checkpoint Inhibitors. 葡萄膜黑色素瘤肝转移的免疫分析和对检查点抑制剂的反应。
IF 2.9 4区 医学
Journal of Immunotherapy Pub Date : 2025-06-01 Epub Date: 2025-04-15 DOI: 10.1097/CJI.0000000000000558
Yusra F Shao, Yasmine Baca, Andrew Hinton, Joanne Xiu, Ari VanderWalde, Matthew Hadfield, Soo J Park, Sourat Darabi, Takami Sato, Justin C Moser
{"title":"Immune Profiling of Uveal Melanoma Liver Metastases and Response to Checkpoint Inhibitors.","authors":"Yusra F Shao, Yasmine Baca, Andrew Hinton, Joanne Xiu, Ari VanderWalde, Matthew Hadfield, Soo J Park, Sourat Darabi, Takami Sato, Justin C Moser","doi":"10.1097/CJI.0000000000000558","DOIUrl":"10.1097/CJI.0000000000000558","url":null,"abstract":"<p><p>Responses to immune checkpoint inhibitors (ICIs) differ significantly between uveal melanoma (UM) and cutaneous melanoma (CM) patients. We investigated the immune profile of metastatic UM(mUM) patients and identified markers that are predictive of improved survival. Metastatic liver samples from 189 UM patients and 48 CM patients were analyzed at genomic and transcriptional levels, and survival analysis was performed on a subgroup of 76 ICI-treated mUM patients. UM liver metastases seem to preserve the genomic and immune characteristics of primary UM (pUM), with a low prevalence of ICI markers and high mutation rates of GNA11, GNAQ, BAP1, and SF3B. Compared with mCM, UM liver metastasis showed lower infiltration of several immune cells, but a greater proportion of M2 macrophages. Compared with UM liver metastases, CM liver metastases showed higher expression of G2M checkpoint and EF2 target genes. Among the mUM and mCM samples, expression of G2M and E2F pathway genes was highest in tumors with high TMB values and T-cell inflamed scores. A longer median overall survival (OS) was observed in mUM patients with higher expression of LAG3, HLA class I, or HLA class II; which may represent a small proportion of immune hot tumors. Expression patterns of G2M checkpoint and E2F targets suggest a possible contribution to immunotherapy response.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":"48 5","pages":"189-195"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022437","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}
引用次数: 0
High Expression of Calreticulin Affected the Tumor Microenvironment and Correlated With Worse Prognosis in Patients With Triple-Negative Breast Cancer. 高表达钙网蛋白影响三阴性乳腺癌患者肿瘤微环境并与不良预后相关
IF 2.9 4区 医学
Journal of Immunotherapy Pub Date : 2025-06-01 Epub Date: 2025-03-24 DOI: 10.1097/CJI.0000000000000553
Xi Cao, Xinyu Ren, Yu Song, Qiang Sun, Feng Mao, Songjie Shen, Chang Chen, Yidong Zhou
{"title":"High Expression of Calreticulin Affected the Tumor Microenvironment and Correlated With Worse Prognosis in Patients With Triple-Negative Breast Cancer.","authors":"Xi Cao, Xinyu Ren, Yu Song, Qiang Sun, Feng Mao, Songjie Shen, Chang Chen, Yidong Zhou","doi":"10.1097/CJI.0000000000000553","DOIUrl":"10.1097/CJI.0000000000000553","url":null,"abstract":"<p><p>Calreticulin (CALR) preserves reticular homeostasis by maintaining correct protein folding within the endoplasmic reticulum. Immunogenic cell death (ICD) is a regulated form of cell death and could activate adaptive immune response. As one of the damage-associated molecular patterns during ICD process, surface-exposed CALR resulted in the activation of adaptive immune response. Here, we evaluated the expression patterns of CALR in a cohort of 231 untreated triple-negative breast cancer (TNBC) and determined correlations between CALR expression and clinicopathologic parameters, programmed cell death ligand 1 (PD-L1) expression in immune cells (ICs), and survival. In addition, we analyzed a TNBC data set from The Cancer Genome Atlas to explore the relationship between mRNA expression of CALR and clinicopathologic features, IC infiltration, and survival. Tissue microarray results showed that high CLAR was strongly correlated with advanced stage ( P = 0.022), shorter disease-free survival ( P = 0.008) and overall survival ( P = 0.002), and independently predicted prognosis in TNBC. Spearman analyses demonstrated that CALR negatively correlated with PD-L1 in ICs ( r = -0.198, P = 0.003). Patients with low CALR and high PD-L1 in ICs had the best disease-free survival ( P = 0.013) and overall survival ( P = 0.004) compared with other patients, especially the patients with high CALR and low PD-L1 in ICs. In the \"The Cancer Genome Atlas\" cohort, CALR mRNA expression in tumors was significantly higher than that in normal tissues ( P < 0.001). CALR expression was strongly and positively related to other ICD-related genes. These findings demonstrated that the expression of CALR could independently predict the prognosis in patients with TNBC, and it may play a potential synergistic role in treatments involving immunotherapy.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"173-182"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12052058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692408","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}
引用次数: 0
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