Ask about this productRelated genes to: CTLA4 antibody
- Gene:
- CTLA4 NIH gene
- Name:
- cytotoxic T-lymphocyte associated protein 4
- Previous symbol:
- CELIAC3, IDDM12
- Synonyms:
- CD152, CD, GSE, CTLA-4
- Chromosome:
- 2q33.2
- Locus Type:
- gene with protein product
- Date approved:
- 1989-05-25
- Date modifiied:
- 2019-04-23
Related products to: CTLA4 antibody
Related articles to: CTLA4 antibody
- Recently, programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors have achieved major breakthroughs in oncology, with 32 drugs approved over the past decade. This advancement has established immunotherapy as the fifth major antitumor modality following surgery, chemotherapy, radiotherapy, and targeted therapy. However, PD-1/PD-L1 inhibitors induce sustained responses in only a limited number of patients, and primary and acquired resistance remain critical challenges in clinical practice. As understanding of the complex crosstalk among cancer cells, the tumor microenvironment, and the host immune system deepens, numerous strategies to overcome PD-1/PD-L1 inhibitor resistance have been proposed. In this review, we examine the current development of PD-1/PD-L1 inhibitors, analyze global approval trends, and evaluate their monotherapy efficacy across various tumor types. As multi-target combination therapy is an essential strategy for overcoming resistance, we analyze key combination targets - such as vascular endothelial growth factor (VEGF), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and lymphocyte activation gene 3 (LAG-3) - and highlight the clinical success of novel dual-target regimens such as ivonescimab (PD-1/VEGF). Furthermore, we discuss potential approaches to overcoming resistance from both microenvironmental (e.g., targeting cancer-associated fibroblasts or utilizing antibody-drug conjugates) and macroenvironmental (e.g., modulating the microbiota or sex hormones) perspectives. This review provides a forward-looking framework for designing precision- and mechanism-driven combination therapies aimed at converting non-responders into responders. - Source: PubMed
Publication date: 2026/05/15
Li LijunZhao YanbinShi XinhongGuo XiaotianZhang XiaoxinLi GuangruiMeng QingweiZhang MinghuiYin Mingzhu - Hepatocellular carcinoma (HCC) remains a lethal malignancy, and robust biomarkers are needed to refine risk stratification and support clinical decision-making. Long noncoding RNAs can shape tumor biology and immune states. We investigated the clinical relevance of lncRNA NRAV in HCC and its association with immune-related features. - Source: PubMed
Publication date: 2026/06/09
Fang XingbaoCai YanLi ZhaojunPeng XiongbingYang ShaohuaZhao ZhuoyuLi Yuehong - We established a novel syngeneic glioblastoma stem cell (GSC) line from PDGFB-driven RCAS/tv-a glioblastomas and subsequently generated a Pten-deficient derivative, WYZ-1. In vitro, WYZ-1 cells exhibited robust self-renewal, high expression of GSC markers (CD133, Nestin, SOX2), and multipotent differentiation into neuronal and astrocytic lineages. In vivo, intracranial implantation in immunocompetent mice produced highly infiltrative and vascularized tumors with marked proliferation, necrosis, and white matter invasion, closely recapitulating key histopathological features of human glioblastoma. Immunohistochemical analysis confirmed the retention of oncogenic, stem-like, and mesenchymal-associated markers. Importantly, WYZ-1 tumors displayed an immune-excluded ("cold") tumor microenvironment characterized by dense infiltration of immunosuppressive macrophages/microglial cells within the tumor core and restricted localization of exhausted T cells to the tumor margins. Consistent with these features, WYZ-1 tumors are resistant to temozolomide and anti-PD-1 monotherapy, with only a modest survival benefit observed following CTLA-4 blockade. Collectively, these findings establish WYZ-1 as a highly aggressive, stem-like, and immunocompetent glioblastoma model that mirrors the therapeutic resistance of human disease and provides a valuable platform for investigating tumor biology and evaluating novel immunotherapeutic strategies. - Source: PubMed
Publication date: 2026/06/09
Xue QingfengYe JuanChakraborty SamikSang XueyuSun MitchellZhang YapingChen ShuranLin WanrunMunasinghe JeevaYang ChunzhangWang HeruiZhuang Zhengping - Skin cutaneous melanoma (SKCM) is a highly aggressive malignancy with rising global incidence and mortality. Despite advances in immunotherapy and targeted therapies, treatment resistance remains a challenge, necessitating novel prognostic biomarkers and therapeutic strategies. Cuproptosis, a copper-dependent form of regulated cell death, and immune-related pathways have emerged as critical players in tumor progression. However, their combined prognostic potential in SKCM remains unexplored. Here, we constructed a cuproptosis-immune-related gene signature to predict SKCM prognosis and guide therapy. Using the TCGA database, we identified 474 cuproptosis-related immune genes through Pearson correlation analysis. By integrating the GTEx database, differential expression analysis revealed that 194 of these genes were significantly dysregulated in SKCM. Univariate Cox and LASSO regression analyses established a 12-gene prognostic model (C3AR1, CCL8, CCR1, CTLA4, HLA-DRB1, IFIH1, IL2RA, IRF9, KIR2DL4, TLR1, TNFRSF21, XCL2), stratifying patients into high- and low-risk groups. The model demonstrated robust predictive accuracy in training and validation cohorts. High-risk patients exhibited poorer survival, reduced immune infiltration, suppressed checkpoint expression, and lower tumor mutational burden (TMB), suggesting an immunosuppressive microenvironment. Conversely, low-risk patients showed enhanced immune infiltration, higher TMB, and increased checkpoint-related gene expression, suggesting an immune-inflamed but functionally restrained phenotype with potential relevance to immune checkpoint blockade. Drug sensitivity analysis revealed high-risk patients may benefit more from targeted therapies. A nomogram integrating risk scores and clinical factors further improved prognostic prediction, with calibration curves demonstrating strong concordance between predicted and observed survival probabilities. Single-cell RNA sequencing illustrated the cellular distribution of model genes, and functional experiments demonstrated that XCL2 suppresses melanoma cell proliferation, migration, and invasion. This study develops and validates a cuproptosis-immune integrated prognostic signature for SKCM, providing a framework to link cuproptosis-associated biology with immune microenvironmental features, risk stratification, and potential therapeutic decision-making. - Source: PubMed
Publication date: 2026/06/09
Zhao MeiruXiao MengZhang XinmeiZhang JunyanLiu TongWang Huiping - Cancer immunotherapy has fundamentally transformed the management of solid tumors, ranging from immune checkpoint blockade to a broader spectrum of immune-modulating strategies. While inhibitors of CTLA-4 and the PD-1/PD-L1 axis remain central to clinical practice, heterogeneous clinical responses, immune-related toxicities, and different resistance mechanisms underscore the need for next-generation approaches. This review integrates recent advances in cancer immunotherapy for solid tumors, with an emphasis on emerging biological concepts and therapeutic platforms that extend beyond classical checkpoint inhibition. We discuss novel immune checkpoints, biomarker-driven approvals, and the expanding role of immunotherapy in different disease settings. Antibody-based platforms are highlighted as strategies that integrate direct tumor targeting with immune activation, which have reshaped standards of care in several malignancies. We further review advances in adoptive cellular therapies as well as next-generation cytokine therapies and cancer vaccines aimed at enhancing tumor-specific immune responses while mitigating systemic toxicity. Finally, we address key unresolved challenges, including mechanisms of resistance, optimization of sequencing and dosing strategies, and clinical trial design considerations. Together, these developments reflect a rapidly evolving field focused on broadening efficacy, improving safety, and personalizing treatment in solid tumors. - Source: PubMed
Publication date: 2026/06/09
Gabizon-Peretz ShiraKluger Harriet M