Critical reviews in oncology/hematology最新文献_第4页

Death receptor 3: A paradoxical biomarker and therapeutic target in pan-cancer 死亡受体3：一个矛盾的生物标志物和泛癌症的治疗靶点

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2026-01-26 DOI: 10.1016/j.critrevonc.2026.105157

Wenxuan Fang , Junfang Du , Zedong Xu , Qiuyu Liu , Yonghong Liu , Xueni Wang

Death receptor 3 (DR3/TNFRSF25) is a member of the tumor necrosis factor receptor superfamily, exhibiting dual roles in regulating tumor apoptosis and metastasis. Through literature review and pan-cancer analysis, this study reveals that DR3 expression exhibits distinct tumor type specificity: it is highly expressed in seven cancers, including Bladder Urothelial Carcinoma (BLCA), while showing low expression in sixteen cancers, such as Adrenocortical carcinoma (ACC). Its expression correlates with CD8⁺ T cell and natural killer (NK) cell infiltration, tumor mutational burden (TMB), and is closely associated with prognosis, exhibiting opposite trends across different cancer types. Mechanistically, DR3 activates apoptosis or programmed necrosis pathways by binding its ligand TL1A. Its interaction with NF-κB exhibits directional discrepancies across cancer types, which differentially regulate cell death. Additionally, DR3 suppresses angiogenesis and modulates antitumor immune responses. While multiple natural and synthetic compounds modulate DR3-related pathways to exert antitumor effects, no direct-targeting drugs are currently available. The presence of DR3 isoforms and decoy receptor DcR3 adds complexity to its signaling, suggesting that future clinical applications require precise evaluation considering the tumor microenvironment. In summary, DR3 is a multifunctional molecule with significant potential as a biomarker and therapeutic target. However, its duality and context-dependent effects necessitate the development of personalized strategies based on tumor molecular subtyping.

死亡受体3 （DR3/TNFRSF25）是肿瘤坏死因子受体超家族的成员，在调节肿瘤凋亡和转移中发挥双重作用。通过文献回顾和泛癌分析，本研究发现DR3表达具有明显的肿瘤类型特异性：在膀胱尿路上皮癌（BLCA）等7种肿瘤中高表达，在肾上腺皮质癌（ACC）等16种肿瘤中低表达。其表达与CD8 + T细胞和自然杀伤细胞（NK）浸润、肿瘤突变负荷（TMB）相关，且与预后密切相关，在不同癌症类型中表现出相反的趋势。在机制上，DR3通过结合其配体TL1A激活凋亡或程序性坏死途径。它与NF-κB的相互作用在不同的癌症类型中表现出方向性差异，从而不同地调节细胞死亡。此外，DR3抑制血管生成和调节抗肿瘤免疫反应。虽然多种天然和合成化合物可调节dr3相关途径发挥抗肿瘤作用，但目前尚无直接靶向的药物可用。DR3亚型和诱饵受体DcR3的存在增加了其信号传导的复杂性，这表明未来的临床应用需要考虑肿瘤微环境的精确评估。综上所述，DR3是一种多功能分子，具有作为生物标志物和治疗靶点的巨大潜力。然而，它的双重性和环境依赖效应需要基于肿瘤分子亚型的个性化策略的发展。

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引用次数: 0

FASN at the crossroads of tumor metabolism, immune evasion, and therapy resistance: Mechanistic insights and therapeutic opportunities FASN在肿瘤代谢、免疫逃避和治疗抵抗的十字路口：机制见解和治疗机会

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2026-01-26 DOI: 10.1016/j.critrevonc.2026.105155

Xuefeng Jiang , Guotao Fang , Wen Li , Yusheng Liu , Gang Chen , Silvio E. Perea , Yasser Perera , Rong Ma , Xiaofei Hu , Xinan Long

Fatty acid synthase (FASN), the key enzyme driving de novo lipogenesis, has emerged as a central metabolic hub in cancer, linking aberrant lipid synthesis to tumor progression, immune escape, and therapy resistance. This review provides a comprehensive overview of the regulatory landscape and oncogenic functions of FASN, highlighting its modulation at transcriptional, post-transcriptional, and post-translational levels. We discuss how FASN-driven lipid remodeling supports tumor proliferation, disrupts antigen presentation, alters immune cell metabolism, and suppresses ferroptosis, thereby enabling resistance to chemotherapy, radiotherapy, targeted therapy, and immune checkpoint inhibitors. Emerging therapeutic strategies—including direct FASN inhibition, targeting upstream regulators, and rational metabolic–immune–ferroptosis combinatorial regimens—are explored in the context of precision oncology. Given the metabolic plasticity of cancer cells and the heterogeneous response of the tumor immune microenvironment, future advances will rely on dynamic biomarker-guided therapy and spatiotemporal profiling of FASN activity. Together, these insights position FASN not merely as a metabolic enzyme but as a versatile therapeutic axis at the intersection of cancer metabolism, immunity, and resistance.

脂肪酸合成酶（FASN）是驱动新生脂肪生成的关键酶，已成为癌症的中心代谢枢纽，将异常脂质合成与肿瘤进展、免疫逃逸和治疗抵抗联系起来。这篇综述提供了FASN的调控前景和致癌功能的全面概述，重点介绍了其在转录、转录后和翻译后水平上的调节。我们讨论了fasn驱动的脂质重塑如何支持肿瘤增殖，破坏抗原呈递，改变免疫细胞代谢，抑制铁下沉，从而使化疗，放疗，靶向治疗和免疫检查点抑制剂产生耐药性。新兴的治疗策略——包括直接抑制FASN，靶向上游调节因子，合理的代谢-免疫-铁下垂联合方案——在精确肿瘤学的背景下进行了探索。鉴于癌细胞的代谢可塑性和肿瘤免疫微环境的异质性反应，未来的进展将依赖于动态生物标志物引导的治疗和FASN活性的时空分析。总之，这些见解使FASN不仅是一种代谢酶，而且是癌症代谢、免疫和耐药性交叉的多功能治疗轴。

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引用次数: 0

Multifaceted mechanisms and precision strategies to overcome therapeutic resistance in gallbladder cancer 克服胆囊癌耐药的多方面机制和精确策略。

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2026-01-25 DOI: 10.1016/j.critrevonc.2026.105152

Qingliang Jiang , Gang Li , Hengyu Li , Xiaoqing Jiang , Daimin Xiang

Gallbladder cancer (GBC) is a rare but highly aggressive malignancy with poor prognosis, largely due to the pervasive challenge of therapeutic resistance. Conventional chemotherapy, targeted therapy, and immunotherapy have shown limited efficacy, as tumor cells rapidly acquire resistance through diverse mechanisms. These include drug metabolism reprogramming, enhanced DNA damage repair, signaling pathway rewiring, epigenetic and non-coding RNA regulation, programmed cell death modulation, immune evasion, and remodeling of the TME. Increasing evidence indicates that resistance in GBC is not driven by a single factor but rather by the dynamic interplay between intrinsic tumor heterogeneity and extrinsic microenvironmental influences. To overcome these barriers, emerging strategies such as multi-target combination regimens, functionalized nanodelivery systems, tumor penetration enhancers, and microbiota-based interventions have demonstrated encouraging potential in preclinical and translational studies. This review provides a comprehensive overview of the multidimensional mechanisms of resistance in GBC and highlights current and emerging strategies aimed at reversing or bypassing these processes. A deeper understanding of key resistance nodes and the rational design of cross-pathway interventions will be essential for improving therapeutic efficacy and long-term survival in patients with GBC.

胆囊癌（GBC）是一种罕见但高度侵袭性的恶性肿瘤，预后差，主要是由于治疗耐药性的普遍挑战。常规化疗、靶向治疗和免疫治疗的疗效有限，因为肿瘤细胞通过多种机制迅速获得耐药性。这些包括药物代谢重编程、DNA损伤修复增强、信号通路重布线、表观遗传和非编码RNA调控、程序性细胞死亡调节、免疫逃避和TME重塑。越来越多的证据表明，GBC的耐药不是由单一因素驱动的，而是由肿瘤内在异质性和外部微环境影响之间的动态相互作用驱动的。为了克服这些障碍，诸如多靶点联合方案、功能化纳米递送系统、肿瘤渗透增强剂和基于微生物群的干预等新兴策略在临床前和转化研究中显示出令人鼓舞的潜力。本综述全面概述了GBC耐药的多维机制，并强调了旨在逆转或绕过这些过程的当前和新兴策略。深入了解关键耐药节点，合理设计交叉通路干预措施，对于提高GBC患者的治疗效果和长期生存至关重要。

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引用次数: 0

Management of adverse events associated with TROP2-targeted antibody-drug conjugates in cancer patients 癌症患者中与trop2靶向抗体-药物偶联物相关的不良事件的管理。

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2026-01-24 DOI: 10.1016/j.critrevonc.2026.105153

Zuer He , Zijia Luo , Peilin Dai , Xiaoli Wang , Jiqiao Yang

Antibody-drug conjugates (ADCs) constitute an innovative category of anti-tumor therapeutics that selectively deliver cytotoxins to tumor cells, improving efficacy and reducing toxicity in comparison to systemic therapy. TROP2 serves as a significant target for ADCs in cancer detection and treatment. TROP2-targeted ADCs have shown promising efficacy in cancer therapy. However, it is essential to monitor expected adverse effects to ensure the anti-tumor efficacy and safety. This review clarifies the mechanisms and toxicological profiles of TROP2-targeted medicines based on clinical trials and recommendations, with the aim of providing solutions for the prevention, detection, and management of related adverse events.

抗体-药物偶联物（adc）是一种创新的抗肿瘤治疗药物，可选择性地将细胞毒素传递到肿瘤细胞，与全身治疗相比，可提高疗效并降低毒性。TROP2是adc在癌症检测和治疗中的重要靶点。以trop2为靶点的adc在癌症治疗中已显示出良好的疗效。然而，监测预期的不良反应是保证抗肿瘤疗效和安全性的必要条件。本文在临床试验和推荐的基础上，阐明了trop2靶向药物的作用机制和毒理学特征，旨在为相关不良事件的预防、检测和管理提供解决方案。

引用次数: 0

Prognostic utility of circulating tumor DNA in classical hodgkin lymphoma: A systematic review and individual participant data bayesian meta-analysis 循环肿瘤DNA在经典霍奇金淋巴瘤中的预后效用：系统评价和个体参与者数据贝叶斯荟萃分析。

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2026-01-23 DOI: 10.1016/j.critrevonc.2026.105154

Amirhossein Shahsavand , Shayan Forghani , Mohammad Amin Kharaghani , Reza Samiee , Rania A. Mekary , Mohammad Mahdi Aliasghari , Sajjad Fattahnia , Mona Daghaieghi , Mohammad Reza Rostami , Tahereh Rostami , Ghasem Janbabai

Over 20 % of patients with Hodgkin lymphoma (HL) experience disease progression after initial treatment. We evaluated the prognostic utility of circulating tumor DNA (ctDNA) in HL patients. We systematically searched PubMed, Embase, the Cochrane Library, Scopus, and Web of Science up to March 22, 2025. Survival data were extracted from Kaplan–Meier curves and digitized to reconstruct individual patient-level datasets. We applied a hierarchical Bayesian model with weakly informative priors to estimate hazard ratios (HRs), restricted mean survival times (RMSTs), along with their 95 % credible intervals (CrI) up to five years for both progression-free survival (PFS) and overall survival (OS). Ten studies, including 1158 patients, were analyzed. Elevated baseline ctDNA was associated with inferior PFS (HR: 2.74; 95 % CrI: 1.30–5.75) and a 5-year RMST loss of 7.7 (1.2–17.3) months. Prognostic strength increased over time, with interim ctDNA positivity showing an HR of 5.99 (3.46–10.13; ΔRMST: 22.7 months; 12.9–33.2) and end-of-treatment ctDNA positivity showing an HR of 13.4 (3.97–41.87; ΔRMST: 39.2 months; 17.7–49.4). High baseline ctDNA was associated with worse OS (HR: 2.49; 1.07–5.80; ΔRMST: 11.6 months; 0.7–27.8). Similarly, positive ctDNA following treatment predicted worse OS (HR: 4.74; 1.60–14.47; ΔRMST: 16.2 months; 3.0–38.1). To conclude, in HL patients, a higher ctDNA concentration was associated with increased disease progression and mortality, with this association intensifying toward the end-of-treatment. Clinical implementation requires standardization of assay methods, validation of prognostic thresholds, and longitudinal assessment of the independent prognostic value of ctDNA.

超过20%的霍奇金淋巴瘤（HL）患者在初始治疗后出现疾病进展。我们评估了循环肿瘤DNA （ctDNA）在HL患者中的预后效用。我们系统地检索了PubMed、Embase、Cochrane Library、Scopus和Web of Science，检索时间截止到2025年3月22日。从Kaplan-Meier曲线中提取生存数据并进行数字化以重建个体患者水平的数据集。我们应用具有弱信息先验的分层贝叶斯模型来估计无进展生存期（PFS）和总生存期（OS）的风险比（hr）、受限平均生存期（RMSTs）及其长达5年的95%可信区间（CrI）。我们分析了10项研究，包括1158名患者。基线ctDNA升高与较差的PFS （HR: 2.74; 95% CrI: 1.30-5.75）和5年RMST损失7.7（1.2-17.3）个月相关。预后强度随着时间的推移而增加，中期ctDNA阳性的HR为5.99 (3.46-10.13；ΔRMST: 22.7个月；12.9 - 33.2)，治疗结束时ctDNA阳性的HR为13.4 （3.97-41.87；ΔRMST: 39.2个月；17.7 - 49.4）。高基线ctDNA与较差的OS相关（HR: 2.49; 1.07-5.80； ΔRMST: 11.6个月；0.7-27.8）。同样，治疗后ctDNA阳性预测更差的OS （HR: 4.74; 1.60-14.47； ΔRMST: 16.2个月；3.0-38.1）。总之，在HL患者中，较高的ctDNA浓度与疾病进展和死亡率增加相关，并且这种关联在治疗结束时增强。临床实施需要检测方法的标准化，预后阈值的验证，以及ctDNA独立预后价值的纵向评估。

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引用次数: 0

Cancer-associated thrombosis in the era of precision oncology: Mechanisms, challenges and future directions 精准肿瘤学时代的癌症相关血栓形成：机制、挑战和未来方向。

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2026-01-23 DOI: 10.1016/j.critrevonc.2026.105151

Chaonan He , Xianghao Dai , Dongyu Feng , Qi Zhou , Wenhong Liu , Ye Xu , Fangfang Tao , Mengjiao Hu

Cancer-associated thrombosis (CAT) is a common and life-threatening complication in cancer patients, leading to poor prognosis and reduced survival rate. The pathophysiology process of CAT is driven by a complex interplay of tumor-related process, including tumor-specific genetic mutations, activation of coagulation cascades, multicellular interactions within the tumor microenvironment, and suppression of the fibrinolytic system. Moreover, anticancer therapies, particularly immune checkpoint inhibitors have been shown to further exacerbate this risk. A profound understanding of these mechanisms is essential for therapeutic advancement, necessitating robust preclinical models that accurately replicate the complex pathological features of the disease. This review synthesizes the core mechanisms of CAT, critically evaluates the strategic application of current CAT models, and highlights recent advances in predictive biomarkers, risk assessment models, and emerging therapeutic targets. By integrating mechanistic insights with translational challenges, this review seeks to inform and guide the development of more effective, targeted interventions for CAT.

癌症相关血栓形成（cancer -associated thrombosis， CAT）是癌症患者常见且危及生命的并发症，导致预后不良，降低生存率。CAT的病理生理过程是由肿瘤相关过程的复杂相互作用驱动的，包括肿瘤特异性基因突变、凝血级联的激活、肿瘤微环境内的多细胞相互作用以及纤维蛋白溶解系统的抑制。此外，抗癌疗法，特别是免疫检查点抑制剂已被证明会进一步加剧这种风险。对这些机制的深刻理解对于治疗进展至关重要，需要强大的临床前模型来准确地复制疾病的复杂病理特征。本文综述了CAT的核心机制，批判性地评估了当前CAT模型的战略应用，并重点介绍了预测生物标志物、风险评估模型和新兴治疗靶点的最新进展。通过将机制见解与转化挑战相结合，本综述旨在为更有效、更有针对性的CAT干预措施的开发提供信息和指导。

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引用次数: 0

NRG1 fusions：The potential targeted treatment in non-small cell lung cancer(NSCLC) NRG1融合：非小细胞肺癌（NSCLC）的潜在靶向治疗

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2026-01-23 DOI: 10.1016/j.critrevonc.2026.105147

Jiantao Zhang , Xiaonu Peng , Haibo Huang, Zheng Zhang

Neuregulin 1 (NRG1) gene fusions represent a rare but clinically actionable oncogenic driver in non-small cell lung cancer (NSCLC). This review synthesizes recent advances in targeted therapies for NRG1 fusion-positive NSCLC, with a focus on the underlying molecular mechanisms, diagnostic methodologies, and emerging clinical evidence. Current evidence demonstrates the therapeutic potential of various approaches, including HER3-directed monoclonal antibodies, pan-HER tyrosine kinase inhibitors (TKIs), HER2-selective TKIs, and novel bispecific antibodies. Clinical data have reported partial responses in approximately 35–40 % of patients treated with HER3-targeted agents, accompanied by a median progression-free survival ranging from 4.6 to 6.2 months. Critical challenges persist, such as intrinsic resistance mediated by the heterogeneity of NRG1 fusion isoforms and compensatory activation of the epidermal growth factor receptor (EGFR) pathway. This comprehensive analysis underscores the unmet need for novel therapeutics and provides a framework for optimizing precision oncology strategies in this molecularly defined NSCLC subset, highlighting the necessity for standardized diagnostic protocols and globally collaborative clinical trials.

神经调节蛋白1 （NRG1）基因融合在非小细胞肺癌（NSCLC）中是一种罕见但临床上可操作的致癌驱动因子。本文综述了NRG1融合阳性NSCLC靶向治疗的最新进展，重点关注潜在的分子机制、诊断方法和新出现的临床证据。目前的证据证明了各种方法的治疗潜力，包括her3定向单克隆抗体、泛her酪氨酸激酶抑制剂（TKIs）、her2选择性TKIs和新型双特异性抗体。临床数据显示，接受her3靶向药物治疗的患者中约有35-40%出现部分缓解，中位无进展生存期为4.6 - 6.2个月。关键的挑战仍然存在，如NRG1融合异质介导的内在抗性和表皮生长因子受体（EGFR）途径的代偿激活。这项全面的分析强调了对新疗法的需求尚未得到满足，并为优化这种分子定义的非小细胞肺癌亚群的精确肿瘤学策略提供了框架，强调了标准化诊断方案和全球合作临床试验的必要性。

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引用次数: 0

KRAS mutations reshape the immunosuppressive tumor microenvironment in triple-negative breast cancer: A novel perspective KRAS突变重塑三阴性乳腺癌的免疫抑制肿瘤微环境：一个新的视角。

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2026-01-23 DOI: 10.1016/j.critrevonc.2026.105150

Yuanhao Lv , Ziyin Zhao , Wenyu Di , Lei Liu , Yiyang Chen , Wei Su , Yinghua Ji , Jiateng Zhong

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by poor prognosis and limited therapeutic options due to the lack of well-defined molecular targets. While conventional studies have primarily focused on tumor cell-intrinsic oncogenic mechanisms, this article presents a novel perspective emphasizing the pivotal role of KRAS mutations in remodeling the tumor microenvironment (TME) of TNBC. Although KRAS mutations are relatively uncommon in TNBC (approximately 2–5 %), their presence is associated with increased tumor aggressiveness, the establishment of an immunosuppressive microenvironment, and poor clinical outcomes. This review systematically explores how KRAS mutations, potentially through the modulation of NADPH oxidase 2 (NOX2) activity, may alter oxidative stress dynamics within the TME. We propose that this axis impairs immune cell function, facilitating immune evasion and therapeutic resistance. This perspective not only deepens our understanding of the mechanisms underlying the malignant progression of TNBC but also provides a theoretical basis for developing novel therapeutic strategies to overcome current treatment challenges.

三阴性乳腺癌（TNBC）是一种侵袭性亚型，其特点是预后差，由于缺乏明确的分子靶点，治疗选择有限。传统的研究主要集中在肿瘤细胞内在的致癌机制上，而本文提出了一个新的观点，强调KRAS突变在TNBC肿瘤微环境（TME）重塑中的关键作用。尽管KRAS突变在TNBC中相对罕见（约2-5%），但它们的存在与肿瘤侵袭性增加、免疫抑制微环境的建立和不良临床结果有关。这篇综述系统地探讨了KRAS突变如何可能通过调节NADPH氧化酶2 （NOX2）活性来改变TME内的氧化应激动力学。我们认为这个轴损害免疫细胞功能，促进免疫逃避和治疗抵抗。这一观点不仅加深了我们对TNBC恶性进展机制的理解，而且为开发新的治疗策略以克服当前的治疗挑战提供了理论基础。

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引用次数: 0

TRAIL-functionalized nanoparticles in cancer therapy: Molecular mechanisms and translational opportunities trail功能化纳米颗粒在癌症治疗中的应用：分子机制和转化机会。

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2026-01-23 DOI: 10.1016/j.critrevonc.2026.105149

Dasari Sahithi , Urushi Rehman , Ramasubbamma Ramaiah , Umme Hani , Garima Gupta , Khang Wen Goh , Prashant Kesharwani

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent anticancer agent capable of selectively triggering apoptosis in malignant cells while sparing normal tissues. Clinical translation of TRAIL is limited by rapid systemic clearance, poor pharmacokinetics, and intrinsic or acquired tumor resistance. Nanotechnology offers innovative solutions by stabilizing TRAIL, enhancing bioavailability, and enabling targeted delivery. Lipid-based, polymeric, and metallic nanoparticles have been engineered to improve TRAIL activity and achieve tumor-specific accumulation. TRAIL-functionalized nanocarriers also facilitate combinatorial strategies, including co-delivery with chemotherapeutics, sensitizers, or immunomodulators, to overcome resistance and potentiate apoptotic signaling. Preclinical studies in triple-negative breast cancer, glioblastoma, and colorectal carcinoma models demonstrate enhanced therapeutic efficacy, reduced systemic toxicity, and significant translational potential. This review critically examines the molecular mechanisms of TRAIL-mediated apoptosis, design principles of TRAIL-conjugated nanoparticles, and their integration into synergistic therapeutic regimens. Current limitations and future directions are discussed, emphasizing strategies to advance TRAIL nanomedicines toward clinical application. Collectively, TRAIL-functionalized nanoparticles represent a promising approach to precision oncology, bridging molecular therapeutics and nanotechnology for personalized cancer treatment.

肿瘤坏死因子相关凋亡诱导配体（Tumor necrosis factor-related apoptosis-inducing ligand， TRAIL）是一种有效的抗癌药物，能够选择性地触发恶性细胞的凋亡，同时保留正常组织。TRAIL的临床翻译受到快速全身清除、不良药代动力学和内在或获得性肿瘤抵抗的限制。纳米技术通过稳定TRAIL、提高生物利用度和实现靶向递送提供了创新的解决方案。脂质、聚合物和金属纳米颗粒已被设计用于改善TRAIL活性并实现肿瘤特异性积累。trail功能化的纳米载体也有助于组合策略，包括与化疗药物、增敏剂或免疫调节剂共同递送，以克服耐药性和增强凋亡信号。在三阴性乳腺癌、胶质母细胞瘤和结直肠癌模型中的临床前研究表明，治疗效果增强，全身毒性降低，并具有显著的转化潜力。本文综述了trail介导的细胞凋亡的分子机制，trail共轭纳米颗粒的设计原则，以及它们与协同治疗方案的结合。讨论了目前的局限性和未来的发展方向，强调了推进TRAIL纳米药物临床应用的策略。总之，trail功能化纳米颗粒代表了一种很有前途的精确肿瘤学方法，将分子治疗和纳米技术连接起来，用于个性化癌症治疗。

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引用次数: 0

Regulatory mechanisms and functions of RORγt⁺ antigen-presenting cells in the tumor microenvironment of non-small cell lung cancer roro γ +抗原提呈细胞在非小细胞肺癌肿瘤微环境中的调控机制及功能

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2026-01-22 DOI: 10.1016/j.critrevonc.2026.105142

Qingze Tan , Weisong Zhang , Yihao Wang , Hao Wang , Rongqi Guo , Hao Zhu , Dongxu Ying , Yeting Li , Xia Li , Jianxiang Song

Non–small cell lung cancer (NSCLC) shows heterogeneity in benefit from immunotherapy across stages and biomarkers, underscoring the need to define tumor-microenvironment (TME) circuits that shape immune activation, spatial organization, and adaptive resistance. Beyond classical APCs, an emerging family of MHC-II⁺, RORγt-expressing APCs—including group 3 innate lymphoid cells (ILC3s), extrathymic AIRE⁺ cells (eTACs), and DC-like populations—has been reported in barrier and lymphoid tissues, shaping type-3 immunity, Th17 differentiation, tolerance, and tertiary lymphoid structure (TLS) biology. Direct phenotypic and functional characterization of bona fide RORγt⁺ APCs in human NSCLC remains limited, and many tumor-derived signals more plausibly reflect RORC-associated, type-3–skewing APC programs rather than confirmed RORγt⁺ identities. In this hypothesis-driven review, we integrate RORγt-linked APC biology, Th17 plasticity, and NSCLC immunobiology to propose a “TME signaling–RORγt-related APC programs–Th17 axis.” To prevent terminology drift, we adopt an evidence-tiered framework distinguishing bona fide RORγt⁺ APCs from inferred RORγt-associated states, and we describe functional variation using module-based descriptors (APC-program–high vs tolerogenic/TLS-linked bias). We further outline how cytokine–chemokine modules—notably CCR6–CCL20—and spatial TLS niches might couple APC programs to Th17 positioning and downstream CD8⁺ T-cell immunity, while emphasizing context-dependent bidirectionality (immune-supportive vs tumor-promoting inflammation). Finally, we highlight two regulatory modules—hypoxia–lactate/adenosine and lipid-ligand tuning of the RORγt ligand-binding domain—as plausible upstream levers that could remodel antigen presentation and type-3 outputs. Translational implications—including RORγt agonism, TME remodeling, and stage-aware biomarker hypotheses with minimally invasive profiling in malignant pleural effusion—are presented as testable hypotheses requiring validation in stage-resolved human NSCLC cohorts and mechanistic studies.

非小细胞肺癌（NSCLC）在不同阶段和生物标志物的免疫治疗中显示出获益的异质性，这强调了定义肿瘤微环境（TME）回路的必要性，这些回路决定了免疫激活、空间组织和适应性抵抗。除了经典的apc之外，一个新兴的MHC-II +家族，表达rorγ t的apc -包括3组先天淋巴样细胞（ILC3s），胸腺外AIRE +细胞（eTACs）和dc样细胞群-已经在屏障和淋巴组织中被报道，形成3型免疫，Th17分化，耐受性和三级淋巴样结构（TLS）生物学。人类NSCLC中真正的roro γ + APC的直接表型和功能表征仍然有限，许多肿瘤来源的信号更合理地反映了rorc相关的3型偏态APC程序，而不是证实的roro γ +身份。在这篇假设驱动的综述中，我们整合了rorγ t相关APC生物学、Th17可塑性和非小细胞肺癌免疫生物学，提出了“TME信号- rorγ t相关APC程序-Th17轴”。为了防止术语漂移，我们采用了一个证据分层的框架，将真实的rorγ γt + apc与推断的rorγ γt相关状态区分开来，并使用基于模块的描述符（apc -程序高偏倚vs耐源性/ tls相关偏倚）描述功能变化。我们进一步概述了细胞因子趋化因子模块（特别是ccr6 - ccl20）和空间TLS利基如何将APC程序与Th17定位和下游CD8 + t细胞免疫结合起来，同时强调上下文依赖性的双向性（免疫支持vs肿瘤促进炎症）。最后，我们强调了两个调控模块——低氧乳酸/腺苷和脂质配体调节的rorγ γt配体结合域——作为可能的上游杠杆，可以重塑抗原呈递和3型输出。翻译意义——包括rorγ - t激动作用、TME重塑和恶性胸腔积液中具有微创谱的分期感知生物标志物假设——被提出为可测试的假设，需要在分期解决的人类NSCLC队列和机制研究中进行验证。

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引用次数: 0