Journal of Immunotherapy最新文献

Comprehensive Analysis of a Dendritic Cell Marker Genes Signature to Predict Prognosis and Immunotherapy Response in Lung Adenocarcinoma. 全面分析树突状细胞标记基因特征以预测肺腺癌的预后和免疫疗法反应

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2025-01-01 Epub Date: 2024-04-29 DOI: 10.1097/CJI.0000000000000521

Peng Song, Yuan Li, Moyan Zhang, Baihan Lyu, Yong Cui, Shugeng Gao

{"title":"Comprehensive Analysis of a Dendritic Cell Marker Genes Signature to Predict Prognosis and Immunotherapy Response in Lung Adenocarcinoma.","authors":"Peng Song, Yuan Li, Moyan Zhang, Baihan Lyu, Yong Cui, Shugeng Gao","doi":"10.1097/CJI.0000000000000521","DOIUrl":"10.1097/CJI.0000000000000521","url":null,"abstract":"With the development of immune checkpoints inhibitors (ICIs), immunotherapy has recently taken center stage in cancer treatment. Dendritic cells exert complicated and important functions in antitumor immunity. This study aims to construct a novel dendritic cell marker gene signature (DCMGS) to predict the prognosis and immunotherapy response of lung adenocarcinoma (LUAD). DC marker genes in LUAD were identified by analysis of single-cell RNA sequencing data. 6 genes ( G0S2, KLF4, ALDH2, IER3, TXN, CD69 ) were screened as the most prognosis-related genes for constructing DCMGS on a training cohort from TCGA data set. Patients were divided into high-risk and low-risk groups by DCMGS risk score based on overall survival time. Then, the predictive ability of the risk model was validated in 6 independent cohorts. DCMGS was verified to be an independent prognostic factor in multivariate analysis. Furthermore, we performed pathway enrichment analysis to explore possible biological mechanisms of the powerful predictive ability of DCMGS, and immune cell infiltration landscape and inflammatory activities were exhibited to reflect the immune profile. Notably, we bridged DCMGS with expression of immune checkpoints and TCR/BCR repertoire diversity that can inflect immunotherapy response. Finally, the predictive ability of DCMGS in immunotherapy response was also validated by 2 cohorts that had received immunotherapy. As a result, the patients with lower DCMGS risk scores showed a better prognosis and immunotherapy response. In conclusion, DCMGS was suggested to be a promising prognostic indicator for LUAD and a desirable predictor for immunotherapy response.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"6-17"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870433","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

Brief Communication on MAGE-A4 and Coexpression of Cancer Testis Antigens in Metastatic Synovial Sarcomas: Considerations for Development of Immunotherapeutics. 关于转移性滑膜肉瘤中 MAGE-A4 和癌症睾丸抗原共表达的简要交流：开发免疫疗法的考虑因素。

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2025-01-01 Epub Date: 2024-09-03 DOI: 10.1097/CJI.0000000000000541

Hélène Vanacker, Robert Connacher, Alexandra Meurgey, Julien Bollard, Valéry Attignon, Franck Tirode, Myriam Jean-Denis, Mehdi Brahmi, Jean-Yves Blay, Ruoxi Wang, Dennis Williams, Armelle Dufresne

{"title":"Brief Communication on MAGE-A4 and Coexpression of Cancer Testis Antigens in Metastatic Synovial Sarcomas: Considerations for Development of Immunotherapeutics.","authors":"Hélène Vanacker, Robert Connacher, Alexandra Meurgey, Julien Bollard, Valéry Attignon, Franck Tirode, Myriam Jean-Denis, Mehdi Brahmi, Jean-Yves Blay, Ruoxi Wang, Dennis Williams, Armelle Dufresne","doi":"10.1097/CJI.0000000000000541","DOIUrl":"10.1097/CJI.0000000000000541","url":null,"abstract":"Therapeutic options for synovial sarcoma (SyS) have not evolved for several decades and the efficacy of second-line treatments is very limited. The expression of a large family of proteins known as cancer testis antigens (CTAs) in SyS has spurred the development of targeted T-cell therapies currently in clinical trials, such as those aimed at melanoma-associated antigen (MAGE)-A4 and New York esophageal squamous cell carcinoma 1 (NY-ESO-1), which have shown promising clinical efficacy. Extensive knowledge of the prevalence of expression and coexpression of CTAs is critical to design T-cell therapies with optimal coverage of the patient population. We analyzed the expression of CTAs of the MAGE-A family as well as NY-ESO-1 and preferentially expressed antigen in melanoma (PRAME) by RNA sequencing in a large cohort of 133 SyS samples from patients registered in the French sarcoma database (NETSARC+). Among MAGE-As, MAGE-A4 had the highest prevalence (65%), followed by MAGE-A10 (15%) and MAGE-A9 (13%). Almost all samples (92%) expressing any of the MAGE-As also expressed MAGE-A4. NY-ESO-1 was expressed in 65% of samples, with a large but incomplete overlap with MAGE-A4, whereas PRAME was present in 121 (91%) samples. Complementary immunohistochemical analyses were used to establish the positive correlation between RNA and protein expression for MAGE-A4 and NY-ESO-1. These data inform the strategy for optimal coverage of the SyS patient population with T-cell therapies, offering patients with SyS new options for single or combined second lines of treatment.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"27-31"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11610908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120027","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

Brief Communication: Combination of an MIP3α-Antigen Fusion Therapeutic DNA Vaccine With Treatments of IFNα and 5-Aza-2'Deoxycytidine Enhances Activated Effector CD8+ T Cells Expressing CD11c in the B16F10 Melanoma Model. 简要通讯：MIP3α-抗原融合治疗性DNA疫苗与IFNα和5-氮杂-2'脱氧胞苷治疗的结合可增强B16F10黑色素瘤模型中表达CD11c的活化效应CD8+T细胞。

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2025-01-01 Epub Date: 2024-10-14 DOI: 10.1097/CJI.0000000000000542

Kaitlyn Fessler, Jiaqi Zhang, Avinaash K Sandhu, Yinan Hui, Aakanksha R Kapoor, Samuel K Ayeh, Styliani Karanika, Petros C Karakousis, Richard B Markham, James T Gordy

{"title":"Brief Communication: Combination of an MIP3α-Antigen Fusion Therapeutic DNA Vaccine With Treatments of IFNα and 5-Aza-2'Deoxycytidine Enhances Activated Effector CD8+ T Cells Expressing CD11c in the B16F10 Melanoma Model.","authors":"Kaitlyn Fessler, Jiaqi Zhang, Avinaash K Sandhu, Yinan Hui, Aakanksha R Kapoor, Samuel K Ayeh, Styliani Karanika, Petros C Karakousis, Richard B Markham, James T Gordy","doi":"10.1097/CJI.0000000000000542","DOIUrl":"10.1097/CJI.0000000000000542","url":null,"abstract":"Previous studies in the B16F10 mouse melanoma model have demonstrated that combining a DNA vaccine comprised of regions of gp100 and tyrosinase-related protein 2 fused to macrophage-inflammatory protein 3-alpha (MIP3α) with recombinant interferon alpha (IFN) and 5-Aza-2'-deoxycytidine (5Aza) treatments resulted in significantly greater antitumor activity and immunogenicity in the tumor microenvironment (TME). This brief report details that the combination of vaccine with treatments IFN and 5Aza results in an increase in the TME of a distinct CD11c+ CD8+ T-cell population. This cell population correlates with tumor size, is primarily comprised of effector or effector memory T cells, and has a more robust response to ex vivo stimulation as compared with CD11c- CD8+ T cells. In conclusion, this combination therapy results in a greater presence of highly active effector CD8+ T cells expressing CD11c in the TME, which are likely primary contributors to treatment efficacy.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"1-5"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11617275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142467476","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

RAD51 Expression as a Biomarker to Predict Efficacy of Platinum-Based Chemotherapy and PD-L1 Blockade for Muscle-Invasive Bladder Cancer. 以 RAD51 表达为生物标记物预测铂类化疗和 PD-L1 阻断剂治疗肌肉浸润性膀胱癌的疗效

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2025-01-01 Epub Date: 2024-05-27 DOI: 10.1097/CJI.0000000000000525

Bingyu Li, Kaifeng Jin, Zhaopei Liu, Xiaohe Su, Ziyue Xu, Ge Liu, Jingtong Xu, Yuan Chang, Yiwei Wang, Yu Zhu, Le Xu, Zewei Wang, Hailong Liu, Weijuan Zhang

{"title":"RAD51 Expression as a Biomarker to Predict Efficacy of Platinum-Based Chemotherapy and PD-L1 Blockade for Muscle-Invasive Bladder Cancer.","authors":"Bingyu Li, Kaifeng Jin, Zhaopei Liu, Xiaohe Su, Ziyue Xu, Ge Liu, Jingtong Xu, Yuan Chang, Yiwei Wang, Yu Zhu, Le Xu, Zewei Wang, Hailong Liu, Weijuan Zhang","doi":"10.1097/CJI.0000000000000525","DOIUrl":"10.1097/CJI.0000000000000525","url":null,"abstract":"RAD51, a key recombinase that catalyzes homologous recombination (HR), is commonly overexpressed in multiple cancers. It is curial for DNA damage repair (DDR) to maintain genomic integrity which could further determine the therapeutic response. Herein, we attempt to explore the clinical value of RAD51 in therapeutic guidance in muscle-invasive bladder cancer (MIBC). In this retrospective study, a total of 823 patients with MIBC were included. Zhongshan hospital (ZSHS) cohort (n=134) and The Cancer Genome Atlas-Bladder Cancer (TCGA-BLCA) cohort (n=391) were included for the investigation of chemotherapeutic response. The IMvigor210 cohort (n=298) was utilized to interrogate the predictive efficacy of RAD51 status to programmed cell death ligand-1 (PD-L1) blockade. In addition, the association of RAD51 with genomic instability and tumor immune contexture was investigated. Patients with RAD51 overexpression were more likely to benefit from both platinum-based chemotherapy and immunotherapy rather than RAD51-low patients. The TMB high PD-L1 high RAD51 high subgroup possessed the best clinical benefits from PD-L1 blockade. RAD51-high tumors featured by genomic instability were correlated to highly inflamed and immunogenic contexture with activated immunotherapeutic pathway in MIBC. RAD51 could serve as a prognosticator for treatment response to platinum-based chemotherapy and PD-L1 inhibitor in MIBC patients. Besides, it could also improve the predictive efficacy of TMB and PD-L1.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"18-26"},"PeriodicalIF":3.2,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141154982","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

Corneal Transplant Rejection Following Durvalumab Therapy in a Patient With NSCLC: A Case Report. 一名 NSCLC 患者接受 Durvalumab 治疗后出现角膜移植排斥反应：病例报告。

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2025-01-01 Epub Date: 2024-07-30 DOI: 10.1097/CJI.0000000000000536

Luise Froessl, Puja Panwar, Subir Bhatia, Jonathan Dowell

引用次数: 0

Efficacy and Safety of Immune Checkpoint Inhibitors on Advanced Cervical Cancer: A Systematic Review and Meta-analysis.

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2024-12-05 DOI: 10.1097/CJI.0000000000000545

Wenhui Wang, Xiaoning Bi, Ye Feng, Xue Ming, Guo Saina, Wang Kun, Bin Ling, Huan Yu

{"title":"Efficacy and Safety of Immune Checkpoint Inhibitors on Advanced Cervical Cancer: A Systematic Review and Meta-analysis.","authors":"Wenhui Wang, Xiaoning Bi, Ye Feng, Xue Ming, Guo Saina, Wang Kun, Bin Ling, Huan Yu","doi":"10.1097/CJI.0000000000000545","DOIUrl":"https://doi.org/10.1097/CJI.0000000000000545","url":null,"abstract":"This study aims to evaluate the efficacy and safety of immune checkpoint inhibitors (ICIs) in patients with histologically proven advanced cervical cancer. MEDLINE (through PubMed), Web of Science, Embase, and the Cochrane Library were comprehensively searched. Eligible studies were clinical trials investigating the efficacy and safety on ICIs in patients with confirmed advanced cervical cancer. Response rates and adverse events rates were pooled using either a random-effects model or a fixed-effects model based on the I2 value. A total of 12 clinical trials with 523 women diagnosed with advanced cervical cancer were included. Programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors were identified. The pooled objective response (OR) rate, complete response (CR) rate, partial response (PR) rate, and stable disease (SD) rate of PD1 antibodies were 0.24 (95% CIs: 0.11-0.39; I2=90%, P<0.01), 0.03 (95% CIs: 0.02-0.05; I2=0%, P =0.92), 0.20 (95% CIs: 0.08-0.36; I2=91%, P<0.01), 0.31 (95% CIs: 0.23-0.40; I2=79%, P<0.01), respectively. Adverse events (AEs) rate of any grade was 0.81 (95% CIs: 0.72-0.88; I2=83%, P<0.01). This study indicates that PD-1/PD-L1 inhibitors reveal acceptable clinical responses and tolerable adverse events in the treatment of advanced cervical cancer. Well-designed clinical trials investigating the efficacy and safety of immune checkpoint inhibitors (ICIs) are needed.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785800","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

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 : 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":""},"PeriodicalIF":3.2,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Generation and Characterization of Ex Vivo Expanded Tumor-infiltrating Lymphocytes From Renal Cell Carcinoma Tumors for Adoptive Cell Therapy. 用于采用细胞疗法的肾细胞癌瘤体外扩增肿瘤浸润淋巴细胞的生成与特征描述

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2024-11-01 Epub Date: 2024-07-15 DOI: 10.1097/CJI.0000000000000533

David J Einstein, Brian Halbert, Thomas Denize, Sayed Matar, Destiny J West, Mamta Gupta, Emanuelle Andrianopoulos, Virginia Seery, Courtney Herman, Kenneth Onimus, Adrian Wells, Brittany Bunch, Sabina Signoretti, Arvind Natarajan, Anand Veerapathran, David F McDermott

{"title":"Generation and Characterization of Ex Vivo Expanded Tumor-infiltrating Lymphocytes From Renal Cell Carcinoma Tumors for Adoptive Cell Therapy.","authors":"David J Einstein, Brian Halbert, Thomas Denize, Sayed Matar, Destiny J West, Mamta Gupta, Emanuelle Andrianopoulos, Virginia Seery, Courtney Herman, Kenneth Onimus, Adrian Wells, Brittany Bunch, Sabina Signoretti, Arvind Natarajan, Anand Veerapathran, David F McDermott","doi":"10.1097/CJI.0000000000000533","DOIUrl":"10.1097/CJI.0000000000000533","url":null,"abstract":"Autologous therapeutic tumor-infiltrating lymphocyte (TIL) therapy is a promising strategy to enhance antitumor immunity. Optimization of ex vivo TIL expansion could expand current immunotherapy options. Previous attempts to generate TIL in renal cell carcinoma (RCC) have been technically challenging. We applied a second-generation manufacturing process, currently used to generate the melanoma TIL product lifileucel, in RCC. Resected primary and metastatic RCC samples were processed using the Gen 2 manufacturing process comprising of pre-Rapid Expansion Protocol (pre-REP) and REP steps. We assessed REP TILs for viability and performed phenotypic and functional characterization. We correlated the tumor immune microenvironment (TIME) with successful TIL expansion. Eight of 11 RCC samples underwent successful REP. Three failed cases demonstrated low CD8/FoxP3 ratio and high expression of PD-1 within FoxP3 cells. Expression of exhaustion markers differed between the TIME and expanded TILs; the latter had a TIM3-high/PD-1-low phenotype but retained functional capacity comparable to lifileucel. The Gen 2 manufacturing process used for lifileucel successfully expanded functional TILs from RCC samples, enabling further study in a clinical trial. TIME features such as low CD8/FoxP3 ratio and high PD-1 expression within FoxP3 cells warrant study as potential biomarkers of successful TIL expansion.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"361-368"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141600244","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

Blood Tumor Mutational Burden Alone Is Not a Good Predictive Biomarker for Response to Immune Checkpoint Inhibitors in Patients With Gastrointestinal Tumors. 仅凭血液肿瘤突变负荷不能很好地预测胃肠道肿瘤患者对免疫检查点抑制剂反应的生物标志物

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2024-11-01 Epub Date: 2024-07-16 DOI: 10.1097/CJI.0000000000000532

James Yu, Robin Park, Ruoyu Miao, Iman Imanirad, Moazzam Shahzad, Jose M Laborde, Todd C Knepper, Christine M Walko, Richard Kim

{"title":"Blood Tumor Mutational Burden Alone Is Not a Good Predictive Biomarker for Response to Immune Checkpoint Inhibitors in Patients With Gastrointestinal Tumors.","authors":"James Yu, Robin Park, Ruoyu Miao, Iman Imanirad, Moazzam Shahzad, Jose M Laborde, Todd C Knepper, Christine M Walko, Richard Kim","doi":"10.1097/CJI.0000000000000532","DOIUrl":"10.1097/CJI.0000000000000532","url":null,"abstract":"There has been a controversy about the predictive value of tissue-TMB-H for immune checkpoint inhibitors (ICIs) with limited data regarding blood-TMB (bTMB) in GI tumors. We aim to evaluate the predictive value of bTMB compared with MSI-H in GI tumors. Patients with unresectable/metastatic GI cancer, harboring either MSS with bTMB-H (≥10 mut/Mb) or dMMR/MSI-H who received ICI were included. We compared ICIs' efficacy between MSS-bTMB-H (N=45) versus MSI-H (N=50) in GI tumors. Ninety-five patients were identified with the majority having colorectal (49.5%) or esophagogastric (34.7%) cancers. MSS-bTMB-H group had more esophagogastric cancer and later-line ICI recipients, with no significant differences in other known prognostic variables. At a median follow-up of 9.4 months, MSI-H group showed superior ORR (58.0% vs. 26.7%), DCR (84.0% vs. 42.2%), DoR (not-reached vs. 7.6 mo), PFS (22.5 vs. 3.8 mo), and OS (Not-reached vs. 10.1 mo) compared with MSS-bTMB-H. Multivariable analysis showed that MSI-H was an independent favorable factor over MSS-bTMB-H for PFS (HR=0.31, CI 0.15-0.63, P =0.001) and OS (HR=0.33, CI 0.14-0.80, P =0.014). MSI-H group showed favorable outcomes compared with MSS-bTMB-16+ (ORR: 58.0% vs. 26.9%; DCR: 84.0% vs. 42.3%; PFS:22.5 vs. 4.0 mo) and MSS-bTMB-20+ (ORR: 58.0% vs. 31.6%; DCR: 84.0% vs. 42.1%; PFS:22.5 vs. 3.2 mo). There was no difference between MSS-bTMB10-15 compared with MSS-bTMB-16+ in ORR, DCR, and PFS, or between MSS-bTMB10-19 compared with MSS-bTMB20+. Regardless of bTMB cutoff at 10, 16, or 20, bTMB-H did not appear to be a predictive biomarker in MSS GI tumors in this retrospective analysis.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"378-383"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141620163","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

Gene and Protein Expression of MAGE and Associated Immune Landscape Elements in Non-Small-Cell Lung Carcinoma and Urothelial Carcinomas. 非小细胞肺癌和尿道癌中 MAGE 及相关免疫景观元素的基因和蛋白表达

IF 3.2 4区医学

Journal of Immunotherapy Pub Date : 2024-11-01 Epub Date: 2024-08-22 DOI: 10.1097/CJI.0000000000000538

Izak Faiena, Sabina Adhikary, Colleen Schweitzer, Stephanie H Astrow, Tristan Grogan, Samuel A Funt, Adrian Bot, Tanya Dorff, Jonathan E Rosenberg, David A Elashoff, Allan J Pantuck, Alexandra Drakaki

{"title":"Gene and Protein Expression of MAGE and Associated Immune Landscape Elements in Non-Small-Cell Lung Carcinoma and Urothelial Carcinomas.","authors":"Izak Faiena, Sabina Adhikary, Colleen Schweitzer, Stephanie H Astrow, Tristan Grogan, Samuel A Funt, Adrian Bot, Tanya Dorff, Jonathan E Rosenberg, David A Elashoff, Allan J Pantuck, Alexandra Drakaki","doi":"10.1097/CJI.0000000000000538","DOIUrl":"10.1097/CJI.0000000000000538","url":null,"abstract":"Melanoma-associated antigen-A (MAGE-A) is expressed in multiple cancers with restricted expression in normal tissue. We sought to assess the MAGE-A3/A6 expression profile as well as immune landscape in urothelial (UC) and non-small cell lung carcinoma (NSCLC). We also assessed co-expression of immune-associated markers, including programmed cell death ligand 1 (PD-L1) in tumor and/or immune cells, and assessed the effect of checkpoint inhibitor treatment on these markers in the context of urothelial carcinoma. We used formalin-fixed paraffin-embedded (FFPE) tissue sections from a variety of tumor types were screened by IHC for MAGE-A and PD-L1 expression. Gene expression analyses by RNA sequencing were performed on RNA extracted from serial tissue sections. UC tumor samples from patients treated with checkpoint inhibitors were assessed by IHC and NanoString gene expression analysis for MAGE-A and immune marker expression before and after treatment. Overall, 84 samples (57%) had any detectable MAGE-A expression. Detectable MAGE-A expression was present at similar frequencies in both tumor tissue types, with 41 (50%) NSCLC and 43 (64%) UC. MAGE-A expression was not significantly changed before and after checkpoint inhibitor therapy by both IHC and NanoString mRNA sequencing. Other immune markers were similarly unchanged post immune checkpoint inhibitor therapy. Stable expression of MAGE-A3/A6 pre and post checkpoint inhibitor treatment indicates that archival specimens harvested after checkpoint therapy are applicable to screening potential candidates for MAGE therapies.","PeriodicalId":15996,"journal":{"name":"Journal of Immunotherapy","volume":" ","pages":"351-360"},"PeriodicalIF":3.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446647/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017707","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