Journal of Immunotherapy最新文献

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":"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.","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.

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":"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.","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

Combined CLEC2d Expression and CD58 Loss Mitigate Rejection of Allogeneic T Cells.

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":"https://doi.org/10.1097/CJI.0000000000000552","url":null,"abstract":"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.","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

The Impact of Chronic Obstructive Pulmonary Disease on Immune Checkpoint Inhibitor Effectiveness in Non-small Cell Lung Cancer: A Population Health Study.

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":"Summary: 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.","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

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":"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.","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

Machine Learning-enhanced Signature of Metastasis-related T Cell Marker Genes for Predicting Overall Survival in Malignant Melanoma. 机器学习增强型转移相关 T 细胞标记基因特征用于预测恶性黑色素瘤的总生存期

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2025-04-01 Epub Date: 2024-11-07 DOI: 10.1097/CJI.0000000000000544

Chaoxin Fan, Yimeng Li, Aimin Jiang, Rui Zhao

{"title":"Machine Learning-enhanced Signature of Metastasis-related T Cell Marker Genes for Predicting Overall Survival in Malignant Melanoma.","authors":"Chaoxin Fan, Yimeng Li, Aimin Jiang, Rui Zhao","doi":"10.1097/CJI.0000000000000544","DOIUrl":"10.1097/CJI.0000000000000544","url":null,"abstract":"In this study, we aimed to investigate disparities in the tumor immune microenvironment (TME) between primary and metastatic malignant melanoma (MM) using single-cell RNA sequencing (scRNA- seq ) and to identify metastasis-related T cell marker genes (MRTMGs) for predicting patient survival using machine learning techniques. We identified 6 distinct T cell clusters in 10×scRNA-seq data utilizing the Uniform Manifold Approximation and Projection (UMAP) algorithm. Four machine learning algorithms highlighted SRGN, PMEL, GPR143, EIF4A2, and DSP as pivotal MRTMGs, forming the foundation of the MRTMGs signature. A high MRTMGs signature was found to be correlated with poorer overall survival (OS) and suppression of antitumor immunity in MM patients. We developed a nomogram that combines the MRTMGs signature with the T stage and N stage, which accurately predicts 1-year, 3-year, and 5-year OS probabilities. Furthermore, in an immunotherapy cohort, a high MRTMG signature was associated with an unfavorable response to anti-programmed death 1 (PD-1) therapy. In conclusion, primary and metastatic MM display distinct TME landscapes with different T cell subsets playing crucial roles in metastasis. The MRTMGs signature, established through machine learning, holds potential as a valuable biomarker for predicting the survival of MM patients and their response to anti-PD-1 therapy.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"97-108"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590740","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

Secondary Hemophagocytic Lymphohistiocytosis Syndrome Developing in a Patient With Chronic Lymphocytic Leukemia Under a Long-term Ibrutinib Therapy: A Case Report and Literature Review. 慢性淋巴细胞白血病患者长期接受依鲁替尼治疗后发生继发性噬血细胞淋巴组织细胞增多综合征：1例报告及文献复习。

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2025-04-01 Epub Date: 2024-12-27 DOI: 10.1097/CJI.0000000000000547

Liang Gao, Lihong Wang, Bingjie Wang, Qian Wang, Xinan Cen, Yujun Dong

{"title":"Secondary Hemophagocytic Lymphohistiocytosis Syndrome Developing in a Patient With Chronic Lymphocytic Leukemia Under a Long-term Ibrutinib Therapy: A Case Report and Literature Review.","authors":"Liang Gao, Lihong Wang, Bingjie Wang, Qian Wang, Xinan Cen, Yujun Dong","doi":"10.1097/CJI.0000000000000547","DOIUrl":"10.1097/CJI.0000000000000547","url":null,"abstract":"Secondary hemophagocytic lymphohistiocytosis (HLH) syndrome, a fatal disorder characterized by NK/T-cell deficiency, cytokine storm, and organ damage, is rare in chronic lymphocytic leukemia (CLL). Ibrutinib, the first generation of irreversible Bruton's tyrosine kinase inhibitor, has been the first-line therapy for CLL. As an off-target effect, it can also block IL-2 inducible T-cell kinase (ITK), which is essential in maintaining normal NK and T-cell functions. Up to now, 4 cases reported secondary HLH developed in CLL patients shortly after ibrutinib therapy, which indicated ibrutinib might be associated with HLH via NK/T cell damage as a result of ITK inhibition. We herein report the first case describing EBV-driven HLH developed in a CLL patient under long-term ibrutinib monotherapy (4 year), also showing concurrent NK and T cell deficiency. Therefore, the relationship between the long-term use of ibrutinib and the pathophysiology of HLH, as well as the mediating role of NK/T cell disorder caused by ITK blockade therein, deserves attention and further studies.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"109-112"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895035","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

Multi-institutional Analysis of Immune-Oncology Combination Therapy for Metastatic MiT Family Translocation Renal Cell Carcinoma.

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2025-04-01 Epub Date: 2025-02-04 DOI: 10.1097/CJI.0000000000000549

Yasser Ged, Amina Touma, Luis Meza Contreras, Roy Elias, Joseph Van Galen, Olivia Cupo, Ezra Baraban, Nirmish Singla, Chung-Han Lee, Sumanta Pal, Matthew Zibelman, Ritesh R Kotecha

{"title":"Multi-institutional Analysis of Immune-Oncology Combination Therapy for Metastatic MiT Family Translocation Renal Cell Carcinoma.","authors":"Yasser Ged, Amina Touma, Luis Meza Contreras, Roy Elias, Joseph Van Galen, Olivia Cupo, Ezra Baraban, Nirmish Singla, Chung-Han Lee, Sumanta Pal, Matthew Zibelman, Ritesh R Kotecha","doi":"10.1097/CJI.0000000000000549","DOIUrl":"10.1097/CJI.0000000000000549","url":null,"abstract":"Summary: Metastatic translocation renal cell carcinomas (mtRCCs) are rare and aggressive tumors with limited treatment options. Recent studies demonstrated promising activity of immune-oncology (IO) combinations in mtRCC. However, the effectiveness of dual IO combinations versus IO plus VEGF-TKI combinations remains unclear. We conducted a retrospective analysis of IO combinations in mtRCC patients at 4 institutions. Eligible patients had confirmed mtRCC by genitourinary pathologist and received IO combination therapy (IO+IO or IO+VEGF-TKI). Clinical data and treatment outcomes were recorded from the start of systemic therapy. Objective response rate (ORR) was retrospectively evaluated, and time to treatment failure (TTF), and overall survival (OS) were compared for IO+IO and IO+VEGF-TKI groups. We identified 22 mtRCC patients who received IO combinations, all confirmed to have TFE3 rearrangement by FISH. Most patients were female (68%) with a median age of 41 years (16-79). Treatment breakdown included: IO+IO (n=8, 36%) and IO+VEGF-TKI (n=14, 64%). In the evaluable patients for the efficacy analysis, ORR was 14% (1/7) for the IO+IO group and 54% (6/11) for the IO+VEGF-TKI group. With a median follow-up of 32.4 months, the median TTF was 1.2 months and 6.2 months in the IO+IO and IO+VEGF-TKI groups, respectively ( P =0.12). There was no statistically significant difference in median OS between both groups, 36.7 months in the IO+IO group and 15.6 months in IO+VEGF-TKI ( P =0.9). Our findings demonstrate that IO+VEGF-TKI resulted in higher ORR and TTF point estimates without statistically detectable differences, compared with IO+IO therapy. Larger studies are needed to validate these findings and optimize treatment selection.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"113-117"},"PeriodicalIF":3.2,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123060","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

Identification of Endoplasmic Reticulum Stress-related Genes for Predicting Prognosis, Immunotherapy Response, and Drug Sensitivity in Thyroid Cancer.

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2025-03-26 DOI: 10.1097/CJI.0000000000000554

Lu Zhao, Shuangmei Zhu, Wenxia Ye, Lifen Chen

{"title":"Identification of Endoplasmic Reticulum Stress-related Genes for Predicting Prognosis, Immunotherapy Response, and Drug Sensitivity in Thyroid Cancer.","authors":"Lu Zhao, Shuangmei Zhu, Wenxia Ye, Lifen Chen","doi":"10.1097/CJI.0000000000000554","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000554","url":null,"abstract":"ER stress has emerged as a promising target for cancer therapy. RNA sequencing data of patients with THCA were obtained from the TCGA database to identify differentially expressed genes associated with ER stress. Signature genes were selected through univariate Cox regression, LASSO, and multivariate Cox regression analyses. The predictive performance of the model was assessed using Kaplan-Meier survival analysis and ROC curves. GSEA was conducted to explore pathway enrichment between high-risk and low-risk groups. The immune landscape of risk groups was characterized using ssGSEA, ESTIMATE and CIBERSORT algorithms. Quantitative real-time PCR was employed to investigate the mRNA expression of the signature genes. Finally, immunotherapy response and potential drug sensitivity were evaluated. The prognostic model based on the signature genes ANK2, APOE, ERP27, FPR2, and NOS1, demonstrated robust predictive performance. GSEA results revealed distinct pathway enrichment patterns in the high-risk and low-risk groups. Furthermore, ssGSEA revealed that low-risk patients exhibited enhanced immune-related functions and increased immune cell infiltration. The RT-qPCR results revealed that in thyroid cancer cells, APOE and ERP27 expression levels were elevated, and ANK1, NOS1, and FPR2 expression levels were decreased. Immunotherapy, as well as Palbociclib and Perifosine, were predicted to be more effective for low-risk patients. Conversely, high-risk patients were more likely to benefit from Axitinib, Imatinib, Nilotinib, and Temsirolimus. This study identified 5 signature genes as potential biomarkers and therapeutic targets for THCA. These findings provide novel insights into the prognosis and targeted therapy of THCA, offering a foundation for furture clinical applications.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710257","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 Immune Checkpoint Inhibitor-induced Thyroid Dysfunction on Cardiac Troponin Levels.

IF 3.2 4区医学

Journal of Immunotherapy Pub 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":"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.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710253","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