Journal of Immunotherapy最新文献

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Effects of Immune Checkpoint Inhibitor-induced Thyroid Dysfunction on Cardiac Troponin Levels. 免疫检查点抑制剂诱导的甲状腺功能障碍对心肌肌钙蛋白水平的影响。
IF 3.2 4区 医学
Journal of Immunotherapy Pub Date : 2025-06-01 Epub Date: 2025-03-25 DOI: 10.1097/CJI.0000000000000555
Yuma Shibutani, Atsushi Kawanobe, Shinya Suzuki, Takuro Imaoka, Kazuko Tajiri
{"title":"Effects of Immune Checkpoint Inhibitor-induced Thyroid Dysfunction on Cardiac Troponin Levels.","authors":"Yuma Shibutani, Atsushi Kawanobe, Shinya Suzuki, Takuro Imaoka, Kazuko Tajiri","doi":"10.1097/CJI.0000000000000555","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000555","url":null,"abstract":"<p><p>Immune checkpoint inhibitor (ICI)-induced thyroid dysfunction is the most frequent endocrine immune-related adverse event (irAE). Thyroid hormones have various effects on the cardiovascular system; however, the impact of thyroid irAEs on the development of cardiovascular diseases is not fully understood. This retrospective study included 94 patients who received ICIs and had thyroid function and troponin T levels, markers of cardiac damage, measured at the National Cancer Center Hospital East between January 2017 and July 2022. Of the 94 patients, 36 (38%) showed elevated troponin levels after ICI treatment during the follow-up period. The median observation period was 249 days (interquartile range, 124-502 d). Thyroid irAEs [hypothyroidism (n=13) and hyperthyroidism (n=3)] associations were found in 16 (44%) of these 36 patients. None of the patients developed overt cardiovascular disease or died of heart disease, regardless of whether they experienced thyroid irAEs. The troponin levels increased with increasing thyroid stimulating hormone (TSH) levels. In particular, troponin levels were significantly elevated in patients with TSH >20 μIU/mL after ICI treatment ( P =0.009). In conclusion, thyroid irAEs may cause cardiac damage indicated by elevated troponin levels, necessitating special attention, particularly in cases of hypothyroidism where TSH exceeds 20 μIU/mL. Therefore, it is important to monitor cardiac markers along with thyroid function after ICI treatment.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":"48 5","pages":"183-188"},"PeriodicalIF":3.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144025507","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
Integrated Single-Cell and Bulk RNA Sequencing Analysis Identifies a Regulated Cell Death-Related Gene Signature for Predicting Prognosis and Therapeutic Responses in Cutaneous Melanoma. 综合单细胞和大体积RNA测序分析确定了预测皮肤黑色素瘤预后和治疗反应的调节细胞死亡相关基因标记。
IF 3.2 4区 医学
Journal of Immunotherapy Pub Date : 2025-05-30 DOI: 10.1097/CJI.0000000000000564
Jie Tang, Shixing Zhu, Linyu Zhu
{"title":"Integrated Single-Cell and Bulk RNA Sequencing Analysis Identifies a Regulated Cell Death-Related Gene Signature for Predicting Prognosis and Therapeutic Responses in Cutaneous Melanoma.","authors":"Jie Tang, Shixing Zhu, Linyu Zhu","doi":"10.1097/CJI.0000000000000564","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000564","url":null,"abstract":"<p><p>Regulated cell death (RCD) is crucial for the advancement of cancers, and providing opportunities as prognostic indicators and immunotherapy markers for patients with cutaneous melanoma (CM). Ten multiomics integrative clustering approaches were performed to identify the CM subtypes. Subsequently, WGCNA was used to screen for module genes. Furthermore, screening hub genes was conducted through machine-learning analyses. Two CM subclasses were identified based on RCD multiomics profiling, each exhibiting distinctive molecular patterns. Then, utilizing the shared cluster DEGs, prognosis DEGs, and key module genes, 30 hub genes were obtained, and an RCD.score was conducted based on these genes. The RCD.score not only reflected the characteristics of the clinical but also provided insights into immunotherapy efficacy. Specifically, low RCD.score category exhibited a more active TME and favorable prognosis, those in the low RCD.score category was more responsive to immunotherapy, suggesting an inflamed TME phenotype. The high RCD.score category had a poor prognosis and was lower responsive to immunotherapy. This research offers genetic support for the possible therapeutic advantages of focusing on RCD in the treatment of CM while also examining their underlying pathophysiological mechanisms.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144187130","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 3.2 4区 医学
Journal of Immunotherapy Pub Date : 2025-05-19 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":"https://doi.org/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":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-19","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 3.2 4区 医学
Journal of Immunotherapy Pub Date : 2025-05-16 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":"https://doi.org/10.1097/CJI.0000000000000563","url":null,"abstract":"<p><strong>Summary: </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":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-16","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 3.2 4区 医学
Journal of Immunotherapy Pub Date : 2025-05-16 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":"https://doi.org/10.1097/CJI.0000000000000561","url":null,"abstract":"<p><strong>Summary: </strong>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":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-16","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
15-Deoxy-Δ-12,14-Prostaglandin J2 Represses Immune Escape of Lung Adenocarcinoma by Polarizing Macrophages Through Epidermal Growth Factor Receptor/Ras/Raf Pathway. 15-Deoxy-Δ-12,14-Prostaglandin J2通过表皮生长因子受体/Ras/Raf通路极化巨噬细胞抑制肺腺癌免疫逃逸
IF 3.2 4区 医学
Journal of Immunotherapy Pub Date : 2025-05-01 Epub Date: 2024-12-23 DOI: 10.1097/CJI.0000000000000546
Fan Jiang, Xiaoxiao Yang, Liqun Shan, Huiwen Miao, Chaohong Shi
{"title":"15-Deoxy-Δ-12,14-Prostaglandin J2 Represses Immune Escape of Lung Adenocarcinoma by Polarizing Macrophages Through Epidermal Growth Factor Receptor/Ras/Raf Pathway.","authors":"Fan Jiang, Xiaoxiao Yang, Liqun Shan, Huiwen Miao, Chaohong Shi","doi":"10.1097/CJI.0000000000000546","DOIUrl":"10.1097/CJI.0000000000000546","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) is a widespread and deadly form of cancer. Prostaglandin 15-deoxy-Δ-12,14-prostaglandin J2 (15d-PGJ2) possesses antioxidant, anti-inflammatory, and anticancer properties. However, it is unclear whether this effect on LUAD progression stems from its ability to influence macrophage polarization. By utilizing 3- (4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, colony formation, transwell assays, and enzyme linked immunosorbent assay (ELISA), we investigated how 15d-PGJ2 affects A549 cell viability, proliferation, apoptosis, and invasion, as well as levels of interleukin (IL)-4, IL-13, and IL-17. Human monocytic cell line THP-1 was induced into M2 macrophages using phorbol 12-myristate 13-acetate and IL-4/IL-13, followed by treatment with 15d-PGJ2. The study employed flow cytometry to observe the polarization of macrophages, quantitative reverse transcription polymerase chain reaction (qRT-PCR) to identify epidermal growth factor receptor (EGFR) expression, western blot for identifying expression of macrophage marker proteins, and examining EGFR/rat sarcoma (Ras)/rapidly accelerated fibrosarcoma (Raf) activation. In a coculture setup, CD8 + T cells were shown to have a proliferation capacity by carboxifluorescein diacetate succinimidyl ester (CFSE), a killing ability by lactate dehydrogenase, and an analysis of their interferon gamma and tumor necrosis factor alpha levels by ELISA. 15d-PGJ2 reduced invasion capacity and expression of inflammatory cytokines, lowered A549 cell viability in a dose-dependent way, and promoted apoptosis. 15d-PGJ2 facilitated the transition of M2 macrophages to the M1 type, inhibited Ras/Raf pathway activation, reduced EGFR expression in macrophages, and stimulated CD8 + T cells to enhance anti-tumor immunity. 15d-PGJ2 repressed M2 macrophage polarization and LUAD immune evasion by targeting the EGFR/Ras/Raf pathway in macrophages.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"119-126"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142877367","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
RBBP8 Is a Prognostic Biomarker Associated With Response to Immune Checkpoint Inhibitors in Advanced Gastric Cancer. RBBP8是与晚期胃癌免疫检查点抑制剂反应相关的预后生物标志物
IF 3.2 4区 医学
Journal of Immunotherapy Pub Date : 2025-05-01 Epub Date: 2025-03-04 DOI: 10.1097/CJI.0000000000000550
Taiki Nakashima, Ryu Matsumoto, Kiyonori Tanoue, Chieri Nakayama, Kazuki Sameshima, Yuto Hozaka, Takaaki Arigami, Daisuke Matsushita, Masataka Shimonosono, Yusuke Tsuruda, Ken Sasaki, Yuko Mataki, Takao Ohtsuka
{"title":"RBBP8 Is a Prognostic Biomarker Associated With Response to Immune Checkpoint Inhibitors in Advanced Gastric Cancer.","authors":"Taiki Nakashima, Ryu Matsumoto, Kiyonori Tanoue, Chieri Nakayama, Kazuki Sameshima, Yuto Hozaka, Takaaki Arigami, Daisuke Matsushita, Masataka Shimonosono, Yusuke Tsuruda, Ken Sasaki, Yuko Mataki, Takao Ohtsuka","doi":"10.1097/CJI.0000000000000550","DOIUrl":"10.1097/CJI.0000000000000550","url":null,"abstract":"<p><p>The current biomarkers for immune checkpoint inhibitor (ICI) therapy have several limitations, and new ones are being explored. Retinoblastoma-binding protein 8 (RBBP8) is associated with tumor-infiltrating immune cells (TIIC) and immune checkpoint molecules. Therefore, RBBP8 may serve as a novel biomarker for ICI therapy. Thus, in this study, we investigated the relationship between RBBP8 expression and the tumor immune environment in 58 patients with pathologic T3-4 gastric cancer who underwent radical gastrectomy. Immunohistochemistry of primary tumor specimens was performed to evaluate RBBP8, TIIC, and programmed cell death ligand 1 expression. Kaplan-Meier survival and prognostic factor analyses were also performed using Cox proportional hazards regression models. Patients were divided into RBBP8 high (HG, n=29) and low (LG, n=29) expression groups, using the median RBBP8 expression as the cutoff. The LG had a significantly worse overall survival rate than the HG (log-rank test, P =0.029). Furthermore, the overall survival rate of patients in LG who were treated with ICI (n=7) was worse than that of those in HG (n=9; log-rank P =0.005). Multivariate analysis identified extensive lymph node metastasis and low RBBP8 expression as independent prognostic factors. The HG and LG showed no significant difference in the number of TIICs; however, there was a difference in the number ratios of CD4+/CD8+ ( P =0.012) and CD4+/CD3+ cells ( P <0.001). Therefore, RBBP8 expression in patients with advanced gastric cancer is a prognostic marker that affects the proportion of CD4+ T-cell infiltration and may also be a biomarker for predicting ICI treatment response.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"147-158"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143541712","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
The Impact of Chronic Obstructive Pulmonary Disease on Immune Checkpoint Inhibitor Effectiveness in Non-small Cell Lung Cancer: A Population Health Study. 慢性阻塞性肺疾病对非小细胞肺癌免疫检查点抑制剂有效性的影响:一项人群健康研究
IF 3.2 4区 医学
Journal of Immunotherapy Pub Date : 2025-05-01 Epub Date: 2025-02-20 DOI: 10.1097/CJI.0000000000000551
Sze Wah Samuel Chan, Gregory R Pond, John R Goffin
{"title":"The Impact of Chronic Obstructive Pulmonary Disease on Immune Checkpoint Inhibitor Effectiveness in Non-small Cell Lung Cancer: A Population Health Study.","authors":"Sze Wah Samuel Chan, Gregory R Pond, John R Goffin","doi":"10.1097/CJI.0000000000000551","DOIUrl":"10.1097/CJI.0000000000000551","url":null,"abstract":"<p><strong>Summary: </strong>Chronic obstructive pulmonary disease (COPD) and lung cancer are associated diseases. COPD confers a negative prognosis in NSCLC, but the clinical benefit of immune checkpoint inhibitors (ICI) in this population is unclear. A population-level analysis of patients in Ontario, Canada was performed through the ICES (formerly known as the Institute for Clinical Evaluative Sciences) administrative database. Patients with NSCLC and treated with PD-1/PD-L1 immune checkpoint inhibitors between Jan 2010 and Dec 2020 were included. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using Cox proportional hazards regression. Hospitalizations and duration of treatment were compared secondarily using logistic and linear regression. A total of 4306 patients received ICI and 54% of patients had a diagnosis of COPD. Median (95% CI) OS was 9.2 (8.5-9.9) months for patients with COPD and 8.2 (7.3-8.8) for patients without COPD, which was not significantly different (adjusted hazard ratio (aHR) = 0.94, 95% CI, 0.87-1.01, P = 0.092). Similarly, the median time on treatment was not different (85 vs. 99 days, multivariable P = 0.10). However, the 90-day hospitalization rate was decreased in the COPD population (multivariable odds ratio 0.76, 95% CI 0.62-0.94, P = 0.011). Among patients with NSCLC receiving ICI, our data suggest that a diagnosis of COPD does not result in shortened treatment, poorer survival, or higher rates of hospitalization. COPD itself should not be considered a contraindication to ICI.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"138-146"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458204","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
Combined CLEC2d Expression and CD58 Loss Mitigate Rejection of Allogeneic T Cells. CLEC2d联合表达和CD58缺失减轻同种异体T细胞的排斥反应。
IF 3.2 4区 医学
Journal of Immunotherapy Pub Date : 2025-05-01 Epub Date: 2025-04-02 DOI: 10.1097/CJI.0000000000000552
Lindsey J Coholan, Cisem Karaca, Faith M Musenge, Moriah L White, Adam J Camblin, Dominique Leboeuf, Colby R Maldini
{"title":"Combined CLEC2d Expression and CD58 Loss Mitigate Rejection of Allogeneic T Cells.","authors":"Lindsey J Coholan, Cisem Karaca, Faith M Musenge, Moriah L White, Adam J Camblin, Dominique Leboeuf, Colby R Maldini","doi":"10.1097/CJI.0000000000000552","DOIUrl":"10.1097/CJI.0000000000000552","url":null,"abstract":"<p><p>Immunogenicity of allogeneic chimeric antigen receptor (CAR) T cell therapies may preclude durable therapeutic responses and broad clinical implementation. Although genetic knockout (KO) of beta-2-microglobulin (B2M) is commonly employed to abrogate HLA class I expression thereby preventing allorecognition by recipient T cells, this deficiency induces missing-self responses by natural killer (NK) cells. Here, we demonstrated that forced expression of a chimeric membrane-bound CLEC2d, an inhibitory ligand of CD161, and concurrent loss of CD58 (LFA-3), an adhesion ligand of CD2, substantially mitigated NK cell responses against allogeneic B2MKO T cells. This combination reduced in vitro NK cell-dependent lysis to a greater extent than either strategy alone and increased the in vivo persistence of these cells after infusion into NK cell-replete humanized mice. Collectively, these findings demonstrate that the convergence of orthogonal genome engineering approaches effectively averts NK cell-driven rejection of allogeneic T cells for immunotherapy.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":"48 4","pages":"127-137"},"PeriodicalIF":3.2,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763638","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
Comparison of Antitumor Effects of Combinations of Immune Checkpoint Inhibitors With Dendritic Cells Intratumorally Injected into Irradiated Mouse Adenocarcinoma. 免疫检查点抑制剂联合树突状细胞瘤内注射辐照小鼠腺癌的抗肿瘤效果比较。
IF 3.2 4区 医学
Journal of Immunotherapy Pub Date : 2025-04-01 Epub Date: 2024-12-27 DOI: 10.1097/CJI.0000000000000548
Ga-Young Park, Woo-Chang Son, Hong-Rae Lee, Eun-Kyoung Koh, Hyun Bon Kang, Jin Hoo Song, Dong Won Kim, YoungHee Kim, You-Soo Park
{"title":"Comparison of Antitumor Effects of Combinations of Immune Checkpoint Inhibitors With Dendritic Cells Intratumorally Injected into Irradiated Mouse Adenocarcinoma.","authors":"Ga-Young Park, Woo-Chang Son, Hong-Rae Lee, Eun-Kyoung Koh, Hyun Bon Kang, Jin Hoo Song, Dong Won Kim, YoungHee Kim, You-Soo Park","doi":"10.1097/CJI.0000000000000548","DOIUrl":"10.1097/CJI.0000000000000548","url":null,"abstract":"<p><p>Dendritic cells (DCs) are specialized immune cells that play a crucial role in presenting antigens and activating cytotoxic T lymphocytes to combat tumors. The immune checkpoint receptor programmed cell death-1 (PD-1) can bind to its ligand programmed cell death-ligand 1 (PD-L1), which is expressed on the surface of cancer cells. This interaction suppresses T-cell activation and promotes immune tolerance. Radiation therapy can increase the expression of PD-L1 on tumor cells, which can lead to a decrease in the effectiveness of the treatment, and detailed studies are needed to understand the mechanisms. As many patients develop resistance to chemotherapy and radiotherapy-either through lack of response or cancer recurrence-there is a critical need to maximize synergistic effects by selecting combination treatments that offer improved therapeutic efficacy with minimal side effects. In the present study, immature DCs (iDCs) were introduced directly into irradiated tumor sites (referred as IR/iDCs), and immune checkpoint blockades (ICBs) were administered intraperitoneally. We confirmed the antitumor effect of combining IR/iDCs and ICBs by examining tumor growth and mouse survival. The proportion of CD4 + and CD8 + T cells in splenocytes increased in the IR/iDCs-treated groups. Combining IR/iDCs with an anti-PD-L1 antibody led to a significant reduction in distant tumor growth and improved mouse survival rates compared with IR/iDCs alone or IR/iDCs + anti-PD-1 antibody. These findings suggest that integrating radiotherapy, DC-based immunotherapy, and ICB, specifically targeting PD-L1, may be an effective cancer treatment strategy.</p>","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"89-96"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895032","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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