Adenosine

Shanghai and Hong Kong, PRC, February 25, 2026 — Antengene Corporation Limited  (“Antengene”, SEHK: 6996.HK) , a leading innovative, commercial-stage global biotech company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for autoimmune diseases, solid tumors and hematological malignancies, announced that it has entered into a clinical collaboration agreement with Shanghai Junshi Biosciences Co., Ltd (“Junshi Biosciences”, SEHK: 1877.HK; SSE: 688180). Under the collaboration, the parties will jointly evaluate the synergistic therapeutic potential of Antengene’s ATG-037, an oral small-molecule CD73 inhibitor, in combination with Junshi Biosciences’ JS207, a recombinant humanized anti-PD-1/VEGF bispecific antibody, in patients with solid tumors in Mainland of China, with the goal of identifying clinical signals across multiple tumor types. This collaboration builds on the encouraging Phase I proof-of-concept clinical data generated with ATG-037. At a time when resistance to checkpoint inhibitors (CPIs) has become a major clinical challenge, the Phase I study evaluating ATG-037 in combination with CPIs has already demonstrated promising potency into reversing CPI resistance. Beyond validating the synergistic potential of these two innovative drugs, this collaboration aims to advance the efficacy of existing immunotherapies and extend the overall survival (OS) of cancer patients through a “triple-axis” approach that incorporates immune checkpoint signalling, anti-angiogenesis, and the alleviation of adenosine-mediated immunosuppression. ATG-037, Antengene’s orally administered small-molecule CD73 inhibitor, offers significant advantages over anti-CD73 monoclonal antibodies. In preclinical studies, ATG-037 demonstrated stronger inhibition of cell-surface CD73 enzymatic activity and overcame the “hook effect” commonly observed with antibody-based approaches. In addition, ATG-037’s higher tissue penetration compared with antibodies may facilitate complete CD73 inhibition at the cellular level. ATG-037 has demonstrated encouraging clinical activity in combination with anti–PD-1 therapy in patients with CPI–resistant melanoma and non-small cell lung cancer (NSCLC), based on the latest data presented at Antengene’s R&D Day in November 2025. In the ongoing Phase I/Ib STAMINA-01 study, the combination achieved an objective response rate (ORR) of 33.3% with a disease control rate (DCR) of 100% in patients with CPI-resistant melanoma, and an ORR of 21.4% with a DCR of 71.4% in patients with CPI-resistant NSCLC. The dataset was generated in Australia in patients with CPI-refractory solid tumors, with pembrolizumab and/or nivolumab as the predominant prior anti–PD-1 therapies, and more than 70% of melanoma patients were refractory to both anti–PD-1 and anti–CTLA-4 (ipilimumab). These results support ATG-037’s clinically meaningful activity across multiple tumor types, particularly in patients with prior immunotherapy resistance. Importantly, ATG-037 has demonstrated a favorable safety and tolerability profile in combination treatment, with no new or unexpected safety signals observed, including in patients receiving long-term therapy. Grade 3 or higher treatment-related adverse events only occurred in 7.9% of patients. Responses have also shown encouraging durability, including a patient who achieved a complete response and has remained on study for over three years and is currently receiving ATG-037 monotherapy for more than a year, as well as multiple patients with durations of response exceeding 12 months. These data support ATG-037’s potential role as a backbone agent for next-generation immuno-oncology combination regimens. JS207, Junshi Biosciences’ independently developed recombinant humanized anti-PD-1/VEGF bispecific antibody, has demonstrated promising anti-tumor activity and a manageable safety profile in both preclinical and clinical studies. JS207’s preclinical studies demonstrated its robust anti-tumor efficacy in multiple tumor models and supported a differentiated mechanism of action, with VEGFA shown to enhance JS207’s antigen binding activity, T-cell activation potency and internalization of cell-surface PD-1. In a poster presented at ESMO Asia 2025, JS207 monotherapy showed encouraging efficacy across solid tumors. 62 patients with PD-L1 positive NSCLC received JS207 monotherapy as first-line treatment, and achieved an ORR of 58.1% and a DCR of 87.1%. Clinical activity has also been observed in additional tumor types, including hepatocellular carcinoma (HCC) and renal cell carcinoma (RCC), supporting the potential of PD-1/VEGF dual targeting across multiple tumor settings. To date, JS207 has 11 ongoing phase II clinical studies, exploring its use in combination with chemotherapy, monoclonal antibodies, antibody-drug conjugates (ADCs) and other drugs in NSCLC, colorectal cancer, triple-negative breast cancer, liver cancer and other tumor types, with nearly 500 patients enrolled. Based on the accumulated data from these studies, the U.S. Food and Drug Administration (FDA) has approved the investigational new drug (IND) application, allowing Junshi Biosciences to initiate an open-label, two-arm, randomized, active-controlled, Phase II/III clinical study comparing JS207 to nivolumab for the neoadjuvant treatment of patients with stage II/III, resectable, actionable genomic aberration (AGA)-negative NSCLC. The scientific rationale for the collaboration is based on the complementary and potentially synergistic mechanisms of CD73 inhibition and dual PD-1/VEGF targeting. CD73 is recognized as a key regulator of immune suppression and angiogenesis within the tumor microenvironment through the generation of adenosine, which can dampen anti-tumor immune responses. In both clinical and preclinical settings, CD73 inhibitors have demonstrated meaningful synergy with anti–PD-1 monoclonal antibodies. In addition, CD73 activity has been shown to promote angiogenesis, including through upregulation of VEGF signaling, and may contribute to the development of resistance to anti-VEGF therapies. Given the broad relevance of immune suppression, angiogenesis and adenosine signaling across solid tumors, this combination strategy has the potential to be applicable across multiple tumor types. Taken together, these observations suggest that combining CD73 blockade with PD-1/VEGF-directed approaches has the potential to enhance and sustain therapeutic effects. Together, the combination of ATG-037 with JS207 represents a potential “triple-axis” approach that simultaneously modulates immune checkpoint signaling, angiogenesis, and the adenosine pathway. With the potential to deepen responses while maintaining a favorable safety profile, the combination of ATG-037 with JS207 may further improve the durability of benefit and may translate into improved OS. We look forward to working closely with Junshi Biosciences and leveraging our respective expertise in target biology and clinical development to accelerate the evaluation of ATG-037 in combination with JS207 across multiple solid tumor types, with the goal of identifying clinical signals and delivering more innovative treatment options for patients in Mainland of China. About Antengene Antengene Corporation Limited (“Antengene”, SEHK: 6996.HK) is a global, R&D-driven, commercial-stage biotech company focused on developing first-in-class/best-in-class therapeutics for diseases with significant unmet medical needs. Its pipeline spans from preclinical to commercial stages and includes several in-house discovered programs, including ATG-022 (CLDN18.2 ADC), ATG-037 (oral CD73 inhibitor), ATG-101 (PD-L1 x 4-1BB bispecific antibody), ATG-031 (CD24-targeting macrophage activator), and ATG-042 (oral PRMT5-MTA inhibitor). Antengene has also developed AnTenGager™, a proprietary T cell engager 2.0 platform featuring “2+1” bivalent binding for low-expressing targets, steric hindrance masking, and proprietary CD3 sequences with fast on/off kinetics to minimize cytokine release syndrome (CRS) and enhance efficacy. These characteristics support the platform’s broad applicability across autoimmune disease, solid tumors and hematological malignancies indications. To date, Antengene has obtained 32 investigational new drug (IND) approvals in the U.S. and Asia, and submitted new drug applications (NDAs) in 11 Asia Pacific markets. Its lead commercial asset, XPOVIO® (selinexor), is approved in Mainland of China, Taiwan China, Hong Kong China, Macau China, South Korea, Singapore, Malaysia, Thailand, Indonesia and Australia, and has been included in the national insurance schemes in five of these markets (Mainland of China, Taiwan China, Australia, South Korea and Singapore). Forward-looking statements   The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development. For a further discussion of these and other factors that could cause future results to differ materially from any forward-looking statement, please see the other risks and uncertainties described in the Company’s Annual Report for the year ended December 31, 2024, and the documents subsequently submitted to the Hong Kong Stock Exchange.

肺癌 1. Gene duplication is associated with gene diversification and potential neofunctionalization in lung cancer evolution. 基因重复与肺癌进化中的功能多样化相关。研究探讨了非小细胞肺癌进化过程中基因拷贝数变化对蛋白质功能的影响。通过开发新型计算协议并结合AlphaFold结构模型，识别出重复后的功能影响事件及潜在的新功能化代谢酶。该发现揭示了肿瘤通过基因重复实现适应性进化的新路径。 非小细胞肺癌, 肿瘤进化 | 基因重复, 蛋白质功能多样化 | 蛋白质结构建模, 演化计算分析 Ashford Paul · … · Orengo Christine A · · 2026/02/19 该研究由结构与分子生物学伦敦大学学院Christine A Orengo团队完成 Genome research 原文链接：https://doi.org/10.1101/gr.278663.123 乳腺癌 1. Development of PROTACs Targeting the Moonlighting Enzyme Nicotinamide Phosphoribosyltransferase (NAMPT) for Breast Cancer Therapy. 针对兼职酶NAMPT的PROTAC降解剂在乳腺癌治疗中的开发。研究旨在通过泛素-蛋白酶体系统选择性降解具有非酶功能的NAMPT蛋白。通过点击化学筛选出的优化降解剂U42在乳腺癌模型中表现出强效的抗增殖活性和良好的药代动力学特性。该研究为利用PROTAC技术靶向兼职蛋白治疗乳腺癌提供了强有力的候选药物。 乳腺癌 | NAMPT, 蛋白质降解 | PROTAC, 点击化学 Galli Ubaldina · … · Grolla Ambra A · · 2026/02/19 该研究由药物科学东皮埃蒙特大学Ambra A Grolla团队完成 Journal of medicinal chemistry 原文链接：https://doi.org/10.1021/acs.jmedchem.5c01827 2. TROP2-targeted NIR-II fluorescence imaging for visualizing surgical margins and metastatic sentinel lymph nodes in breast cancers. TROP2靶向二区荧光成像助力乳腺癌手术。术中实时可视化肿瘤边缘和转移性前哨淋巴结是早期乳腺癌手术面临的重大挑战。研究开发了靶向TROP2的NIR-II荧光探针TTP-ICG，在临床前模型和患者中实现了恶性组织的高灵敏度识别。该探针具有显著的临床转化潜力，可引导精准手术切除并优化腋窝管理。 乳腺癌, 淋巴结转移 | TROP2 | NIR-II荧光成像, 荧光引导手术 Lou Kang-Liang · … · Zhang Guo-Jun · · 2026/02/19 该研究由肿瘤学昆明医科大学第三附属医院张国君团队完成 Proceedings of the National Academy of Sciences of the United States of America 原文链接：https://doi.org/10.1073/pnas.2519420123 3. Association of retinoids, retinoic acid receptors and epigenetics in breast cancer 表观遗传调控视黄酸受体在乳腺癌治疗中的潜力。视黄酸信号在调节细胞分化中起核心作用，但在乳腺癌中的治疗潜力因受体表观遗传失活而受到限制。本文综述了启动子高甲基化等机制如何导致视黄酸耐药，并探讨了表观遗传药物联用视黄酸重塑肿瘤微环境的策略。该研究强调了基于生物标志物的患者分层对实现视黄酸在乳腺癌临床治疗中价值的重要性。 乳腺癌耐药 | 视黄酸受体(RARs), 表观遗传调控 | 综述 Szymański, Łukasz · … · Zelent, Arthur · · 2026/02/20 该研究由血液肿瘤学迈阿密大学Arthur Zelent团队完成 Oncogene 原文链接：http://dx.doi.org/10.1038/s41388-026-03699-8 血液肿瘤 1. Withaferin A inhibits EBV-driven lymphomagenesis through multiple mechanisms, including EBNA1 degradation 醉茄素A通过降解EBNA1等多种机制抑制EB病毒诱导的淋巴瘤发生。EB病毒（EBV）与多种恶性淋巴瘤的发生密切相关，目前仍缺乏针对性的有效治疗手段。研究发现醉茄素A能诱导EBV关键蛋白EBNA1的降解，并干扰多条致癌信号通路，从而显著抑制淋巴瘤细胞的增殖。该研究揭示了醉茄素A作为EBV相关肿瘤治疗药物的潜力，为开发新型抗病毒抗肿瘤药物提供了思路。 淋巴瘤 | EBNA1降解 | 药物筛选 Stewart, Jessica · Damania, Blossom · · 2026/02/19 该研究由病毒肿瘤学北卡罗来纳大学Blossom Damania团队完成 Blood 原文链接：https://www.sciencedirect.com/science/article/pii/S0006497125025704?dgcid=rss_sd_all 2. Age-adapted chemotherapy and MRD-oriented transplant for Ph-negative acute lymphoblastic leukemia: the GRAALL-2014 trial GRAALL-2014试验评估年龄适配化疗与MRD导向移植治疗Ph阴性急性淋巴细胞白血病。Ph阴性急性淋巴细胞白血病（ALL）患者的预后受年龄和微小残留病（MRD）状态的显著影响。本研究通过GRAALL-2014临床试验，验证了根据年龄调整化疗强度并依据MRD水平决定是否进行造血干细胞移植的策略能有效改善患者生存。该研究为Ph阴性ALL的个体化精准治疗提供了高质量的临床证据。 急性淋巴细胞白血病 | 微小残留病 | 临床试验 Boissel, Nicolas · … · Dombret, Hervé · · 2026/02/19 该研究由血液肿瘤学巴黎大学Hervé Dombret团队完成 Blood 原文链接：https://www.sciencedirect.com/science/article/pii/S0006497125035980?dgcid=rss_sd_all 3. The conundrum of drug development in higher-risk MDS: lessons learned from recently failed phase 3 clinical trials 高危骨髓增生异常综合征药物研发的困境与三期临床试验失败的教训。高危骨髓增生异常综合征（MDS）的治疗选择有限，近期多个三期临床试验的失败凸显了研发难度。本文系统总结了近期失败的临床试验案例，分析了试验设计、患者选择及生物学异质性对结果的影响。该综述为未来MDS新药研发的试验设计和策略优化提供了重要的参考和指导。 骨髓增生异常综合征 | 药物研发 | 临床试验分析 Stahl, Maximilian · Zeidan, Amer M. · · 2026/02/19 该研究由血液肿瘤学耶鲁大学Amer M. Zeidan团队完成 Blood 原文链接：https://www.sciencedirect.com/science/article/pii/S0006497125037140?dgcid=rss_sd_all 4. Immunometabolic determinants of long-term response in leukemia patients receiving CD19 CAR T cell therapy 免疫代谢特征决定白血病患者CAR T疗法的长期疗效。尽管CD19 CAR T疗法在白血病中效果显著，但许多患者因CAR T细胞功能丧失而复发，其背后的代谢机制尚待阐明。研究发现长期缓解者的CAR T细胞具有更高的氧化磷酸化和脂肪酸氧化水平，且通过抑制mTOR可诱导代谢重编程增强抗肿瘤活性。该发现揭示了CAR T细胞功能的代谢决定因素，为提高血液肿瘤的长期缓解率提供了新策略。 B细胞急性淋巴细胞白血病 | CAR T细胞代谢, mTOR通路 | 免疫代谢分析 Goldberg, Lior · … · Wang, Xiuli · · 2026/02/20 该研究由肿瘤免疫希望之城国家医疗中心Wang Xiuli团队完成 Nature Communications 原文链接：http://dx.doi.org/10.1038/s41467-026-69857-4 5. Artificial intelligence differentiates prefibrotic primary myelofibrosis with thrombocytosis from essential thrombocythemia using digitized bone marrow biopsy images 人工智能通过骨髓活检图像区分骨髓增生性肿瘤亚型。原发性骨髓纤维化前期与真性红细胞增多症临床特征重叠，常导致诊断不确定性。研究开发了一个具有可解释性的AI框架，通过量化骨髓细胞密度和脂肪比例，以92.3%的准确率实现了两种疾病的自动鉴别。该AI辅助诊断工具揭示了传统标准之外的形态学线索，展示了人工智能增强病理评估的巨大潜力。 骨髓增生性肿瘤(MPN) | 骨髓形态学特征 | 人工智能(AI), 图像识别 Srisuwananukorn, Andrew · … · Hoffman, Ronald · · 2026/02/20 该研究由血液学西奈山伊坎医学院Ronald Hoffman团队完成 Leukemia 原文链接：http://dx.doi.org/10.1038/s41375-026-02893-7 消化肿瘤 1. The deubiquitinase USP17 regulates the expression and activity of the oncogenic driver β-catenin in colorectal cancer. 标题：去泛素化酶USP17调节结直肠癌中β-catenin活性。背景：Wnt/β-catenin信号通路的异常激活是结直肠癌的标志，寻找调节该通路的关键因子具有重要意义。发现：研究证实USP17通过直接去泛素化增强β-catenin稳定性，从而促进肿瘤细胞增殖和上皮间质转化。价值：该研究确立了USP17作为β-catenin信号的关键调节者，并强调了其作为结直肠癌治疗靶点的潜力。 结直肠癌 | USP17, β-catenin, 去泛素化 | CRISPR/Cas9, 蛋白质组学 Acevedo Mariana · … · Servant Marc J · · 2026/02/19 该研究由药学领域蒙特利尔大学Marc J Servant团队完成 Oncogene 原文链接：https://doi.org/10.1038/s41388-026-03695-y 2. The consensus molecular subtypes of esophageal squamous cell carcinoma. 标题：食管鳞癌共识分子分型系统的建立。背景：食管鳞癌缺乏标准化的分类系统，导致临床管理不一且预后较差，亟需精准的分型工具。发现：研究确定了四种共识分子亚型（ECMS），并开发了基于深度学习的病理图像分类框架imECMS。价值：该系统为食管鳞癌的精准医疗提供了稳健的生物学基础和临床分层工具。 食管鳞癌 | 分子亚型, 肿瘤异质性 | 深度学习, 空间组织特征分析 Cui Heyang · … · Cui Yongping · · 2026/02/19 该研究由食管癌精准诊疗领域山西白求恩医院崔永萍团队完成 Signal transduction and targeted therapy 原文链接：https://doi.org/10.1038/s41392-026-02577-9 3. Spatial multiomics reveals irreversible electroporation-induced immuno-metabolic characteristics of the inflammatory margin in liver cancer. 标题：空间多组学揭示肝癌消融后的免疫代谢特征。背景：不可逆电穿孔（IRE）是肝癌的消融疗法，但其诱导的炎症边缘区的免疫和代谢改变尚不明确。发现：通过空间转录组和代谢组学，研究发现炎症边缘区存在脂质代谢重编程及免疫抑制性巨噬细胞浸润。价值：该研究揭示了IRE特异性的免疫抑制微环境，为提高消融治疗效果提供了潜在代谢靶点。 肝癌, 肿瘤消融 | 脂质代谢重编程, 脂质相关巨噬细胞 (LAMs) | 空间转录组学, 空间代谢组学 Liu Jingqi · … · Jiang Tianan · · 2026/02/20 该研究由超声医学领域浙江大学蒋天安团队完成 Communications biology 原文链接：https://doi.org/10.1038/s42003-026-09742-4 4. IL-1β as Target to Induce Synthetic Lethality in KRAS Mutant Biliary Tract Cancer. 标题：IL-1β作为KRAS突变胆管癌的合成致死靶点。背景：KRAS突变在胆管癌中常见且导致治疗耐药，寻找基于合成致死策略的新靶点具有重要临床意义。发现：研究发现抑制GATA2/IL-1β轴能特异性降低KRAS突变胆管癌的活力，并验证了双硫仑的疗效。价值：该研究为KRAS突变胆管癌及其他相关癌症提供了一种潜在的精准治疗策略。 胆管癌, KRAS突变 | GATA2, IL-1β, 合成致死 | 药物筛选, 患者来源异种移植物 (PDX) Li Shijie · … · Chen Mingyu · · 2026/02/20 该研究由普通外科领域浙江大学陈明宇团队完成 Clinical and molecular hepatology 原文链接：https://doi.org/10.3350/cmh.2025.1278 5. Colonoscopy and fecal immunochemical testing versus usual care in diagnostic colorectal cancer screening: the SCREESCO randomized controlled trial 结肠镜与粪便免疫化学检测提升早期结直肠癌检出率。结直肠癌筛查指南推荐使用结肠镜或FIT，但仍需大规模随机试验量化其相对于常规护理的获益与风险。SCREESCO试验显示，结肠镜和FIT筛查均显著增加了早期（I-II期）结直肠癌的诊断比例，尽管初期不良事件略有增加。该研究证实了群体筛查在早期癌症发现中的价值，为优化结直肠癌筛查策略提供了重要临床证据。 结直肠癌筛查 | 早期诊断 | 结肠镜, 粪便免疫化学检测(FIT) Westerberg, Marcus · … · Forsberg, Anna · Nature Medicine · 2026/02/20 ⭐ 该研究由临床流行病学乌普萨拉大学Anna Forsberg团队完成 原文链接：http://dx.doi.org/10.1038/s41591-026-04225-9 妇科肿瘤 1. Lenvatinib plus pembrolizumab in previously treated advanced endometrial cancer: 5-year outcomes from the randomized, phase 3 Study 309/KEYNOTE-775. 仑伐替尼联合帕博利珠单抗治疗晚期子宫内膜癌的5年随访。Study 309/KEYNOTE-775研究报告了该联合疗法对比化疗的长期生存数据。结果显示，无论错配修复状态如何，联合治疗组的5年生存率和无进展生存率均显著优于化疗组。该研究为该方案作为晚期子宫内膜癌的标准治疗提供了强有力的长期证据。 晚期子宫内膜癌 | PD-1抑制, 多靶点激酶抑制 | 随机对照临床试验(Phase 3) Makker Vicky · … · Lorusso Domenica · · 2026/02/19 该研究由生物医学人类大学Domenica Lorusso团队完成 Journal for immunotherapy of cancer 原文链接：https://doi.org/10.1136/jitc-2025-013713 神经肿瘤 1. CSF proteomics identifies ADGRG1 as a predictive biomarker of intrathecal immune checkpoint inhibitor response in leptomeningeal metastasis. 脑脊液蛋白质组学预测软脑膜转移的免疫治疗反应。研究通过对接受鞘内免疫检查点抑制剂治疗的软脑膜转移患者进行脑脊液蛋白谱分析，旨在寻找疗效预测标志物。识别出ADGRG1等五种蛋白组成的特征谱能高精度预测治疗响应。该研究首次描绘了鞘内免疫治疗诱导的免疫重塑图谱，具有重要的临床指导意义。 软脑膜转移, 肿瘤免疫治疗 | ADGRG1, 巨噬细胞生物学 | 脑脊液蛋白质组学, 机器学习建模 Wang Lishi · … · Pan Zhenyu · · 2026/02/19 该研究由放射肿瘤学首都医科大学附属北京胸科医院潘振宇团队完成 Journal for immunotherapy of cancer 原文链接：https://doi.org/10.1136/jitc-2025-013588 2. A spatially resolved human glioblastoma atlas reveals distinct cellular and molecular patterns of anatomical niches. 标题：空间多模态图谱揭示胶质母细胞瘤解剖生态位。背景：胶质母细胞瘤的高度异质性限制了治疗效果，恶性细胞与血管、免疫细胞的空间组织关系尚不清晰。发现：研究构建了整合基因表达与亚细胞分辨率蛋白质测量的空间图谱，识别出与复发相关的特定细胞状态。价值：该高分辨率图谱为研究胶质母细胞瘤的空间组织和寻找治疗靶点提供了重要框架。 胶质母细胞瘤 | 肿瘤微环境, 血管基质相互作用 | 空间转录组学, 亚细胞分辨率成像 Sonpatki Pranali · … · Shah Nameeta · · 2026/02/20 该研究由肿瘤生物信息学领域Amaranth Medical Analytics团队完成 Nature communications 原文链接：https://doi.org/10.1038/s41467-026-69716-2 罕见癌种 1. Modulation of the intestinal microbiome and reversal of the immunosuppressive microenvironment by nanoparticles for chemoimmunotherapy in prostate cancer. 纳米颗粒通过调节肠道菌群增强前列腺癌化疗免疫疗效。针对前列腺癌的免疫抑制微环境，研究开发了一种pH/ROS双响应纳米颗粒。该系统在抑制肿瘤的同时能减轻肠道损伤并优化菌群结构，从而促进T细胞浸润。该策略通过逆转免疫抑制，显著提升了前列腺癌的综合治疗效果。 前列腺癌, 免疫抑制 | 肠道菌群调节, T细胞浸润 | 响应性纳米颗粒, 粪菌移植 Xu Jie · … · Shen Wenhao · · 2026/02/17 该研究由泌尿外科学陆军军医大学西南医院沈文浩团队完成 Journal of advanced research 原文链接：https://doi.org/10.1016/j.jare.2026.02.027 泛癌种 1. Extracellular GPX4 impairs antitumor immunity via dendritic ZP3 receptors 胞外GPX4通过树突状细胞ZP3受体损害抗肿瘤免疫。肿瘤微环境中的铁死亡相关分子如何调节免疫逃逸是当前肿瘤免疫研究的热点。研究发现肿瘤细胞分泌的GPX4能与树突状细胞表面的ZP3受体结合，抑制其抗原递呈功能，从而削弱T细胞介导的抗肿瘤反应。该研究揭示了GPX4在免疫调节中的新功能，为开发提升免疫治疗效果的新策略提供了理论依据。 肿瘤免疫逃逸 | GPX4, ZP3受体 | 免疫学实验 Liu, Jiao · … · Wang, Jiayi · Cell · 2026/02/19 ⭐ 该研究由肿瘤学复旦大学王嘉漪团队完成 原文链接：https://www.sciencedirect.com/science/article/pii/S0092867425013789?dgcid=rss_sd_all 2. LOAd703-induced tumor microenvironment gene engineering in combination with atezolizumab in metastatic malignant melanoma: a phase I/II trial. 基因工程病毒联合免疫检查点抑制剂治疗黑色素瘤。针对PD-1抑制剂耐药的晚期黑色素瘤，研究评估了瘤内注射编码CD40L和4-1BBL的病毒联合阿替利珠单抗的疗效。临床I/II期试验显示该疗法安全性良好，并能通过重塑肿瘤微环境诱导免疫激活。该研究为克服免疫治疗耐药提供了新的临床策略。 恶性黑色素瘤 | CD40L, 4-1BBL, PD-L1 | 基因工程病毒, 临床试验 Hamid O · … · Ullenhag G J · · 2026/02/16 该研究由肿瘤免疫学乌普萨拉大学Ullenhag G J团队完成 Nature communications 原文链接：https://doi.org/10.1038/s41467-026-69629-0 3. A Folate Receptor β-Targeted TLR7 Agonist Significantly Augments Checkpoint Inhibitor Potencies by Reprogramming Tumor-Associated Macrophages and Myeloid-Derived Suppressor Cells. 靶向叶酸受体β的TLR7激动剂增强免疫检查点抑制剂疗效。研究旨在通过重塑肿瘤相关巨噬细胞（TAMs）和髓源性抑制细胞（MDSCs）来克服免疫治疗耐药。核心发现是叶酸-TLR7偶联物能将抑制性髓系细胞重编程为促炎表型，显著提升抗PD-1/CTLA-4的抗肿瘤效力。该研究为提高实体瘤免疫治疗响应率提供了精准靶向新思路。 肿瘤免疫逃逸 | 叶酸受体β, TLR7, 肿瘤相关巨噬细胞 | 偶联药物, 免疫治疗 Napoleon John V · … · Low Philip S · · 2026/02/17 该研究由药物研发普渡大学Philip S Low团队完成 Journal of medicinal chemistry 原文链接：https://doi.org/10.1021/acs.jmedchem.5c03277 4. Co-delivery of a STING agonist and indoleamine 2,3-dioxygenase 1 blockade activates type I dendritic cells in cancer. 协同递送STING激动剂与IDO1抑制剂激活I型树突状细胞。研究针对STING激动剂单药疗效有限的问题，探讨了IDO1介导的耐药机制。发现利用纳米系统共同递送两者可显著增强cDC1的抗原交叉呈递和成熟，从而诱导强效细胞毒性T细胞反应。该研究为克服肿瘤免疫耐受提供了一种高效的集成纳米药物递送方案。 肿瘤免疫耐受 | STING通路, IDO1, I型树突状细胞 | 纳米递送系统 Xia Yanming · … · Li Suxin · · 2026/02/15 该研究由药剂学中国药科大学李苏欣团队完成 Journal of controlled release : official journal of the Controlled Release Society 原文链接：https://doi.org/10.1016/j.jconrel.2026.114731 5. Exogenous Epstein-Barr virus nuclear antigen 1 induces ADAR1-driven tumor resistance against immunotherapy. EB病毒蛋白EBNA1通过ADAR1介导的RNA编辑诱导肿瘤免疫耐药。研究探讨了病毒病原体导致肿瘤对免疫检查点阻断疗法产生耐药的机制。发现EBNA1通过增强ADAR1的翻译来增加RNA编辑，从而掩盖免疫刺激信号并抑制干扰素通路。该研究表明靶向EBNA1可将“冷”肿瘤转变为免疫治疗敏感的“热”肿瘤。 肿瘤免疫耐药 | EBNA1, ADAR1, RNA编辑 | PROTAC降解剂, 免疫治疗 Liu Changlin · … · Li Xin · · 2026/02/18 该研究由病毒肿瘤学南方医科大学李欣团队完成 Signal transduction and targeted therapy 原文链接：https://doi.org/10.1038/s41392-026-02574-y 6. Lipid nanoparticle-mediated in vivo generation of panCAR immune cells for solid tumor immunotherapy. LNP介导的体内泛CAR免疫细胞生成。实体瘤免疫治疗受限于免疫抑制微环境及体外细胞操作的复杂性。研究开发了一种免疫细胞亲和性LNP平台，通过全身递送mRNA在体内生成多谱系CAR免疫细胞，显著抑制肿瘤生长。该平台为实体瘤提供了一种通用的、现成的体内CAR细胞治疗方案。 实体瘤, 免疫抑制微环境 | HER2, CAR-T/NK/巨噬细胞 | 脂质纳米颗粒(LNP), mRNA递送 Yin Qimeng · … · Qiu Min · · 2026/02/19 该研究由生物纳米医学复旦大学Qiu Min团队完成 Proceedings of the National Academy of Sciences of the United States of America 原文链接：https://doi.org/10.1073/pnas.2509698123 7. Rewiring STAT signaling from the cell surface with Trikine immunotherapeutics. Trikine免疫疗法重构STAT信号通路。细胞因子在激活免疫细胞的同时常伴随治疗副作用，限制了其临床应用。研究设计了“Trikines”三链受体复合物，通过诱导定制的STAT信号程序，增强T细胞干性并改善肿瘤控制。该技术无需细胞工程即可定制免疫信号，为实体瘤免疫治疗提供了新工具。 实体瘤, 免疫逃逸 | STAT信号通路, 细胞因子受体 | 蛋白质工程, Trikine Rodriguez Grayson E · … · Garcia K Christopher · Science (New York, N.Y.) · 2026/02/19 ⭐ 该研究由分子与细胞生理学斯坦福大学K. Christopher Garcia团队完成 原文链接：https://doi.org/10.1126/science.adx9954 8. The oncogenome of the domestic cat. 家猫癌症基因组图谱揭示跨物种相似性。癌症是家猫发病和死亡的主因，但其肿瘤突变景观此前尚不明确。研究通过对493对猫肿瘤样本进行靶向测序，鉴定了31个驱动基因及关键突变特征。该成果证实了猫作为比较肿瘤学模型的价值，助力“同一健康”诊疗。 猫科肿瘤 | TP53突变, 驱动基因 | 靶向测序, 比较基因组学 Francis Bailey A · … · van der Weyden Louise · Science (New York, N.Y.) · 2026/02/19 ⭐ 该研究由肿瘤基因组学维康桑格研究所van der Weyden Louise团队完成 原文链接：https://doi.org/10.1126/science.ady6651 9. Scientists decry rush to loosen radiation standards. 科学家反对放宽辐射标准以防癌症风险。针对政府推动核能发展而试图放宽辐射安全标准的举措，研究人员表达了强烈担忧。文章指出，降低标准可能导致癌症病例增加，危及公众健康。这一争议凸显了能源政策与公共卫生安全之间的激烈博弈。 辐射致癌风险 | 辐射安全标准 | 政策评估 Cornwall Warren · Science (New York, N.Y.) · 2026/02/19 原文链接：https://doi.org/10.1126/science.aeg5593 10. Hypoxia-responsive paclitaxel prodrugs: linker evaluation and NIR-triggered self-amplifying photodynamic-chemotherapy nanoplatform. 缺氧响应性紫杉醇前药提升肿瘤化疗精准度。研究系统评价了五种缺氧响应连接体，鉴定出NFA修饰的前药具有最高的药物释放效率。基于此构建的纳米平台结合了光动力治疗与缺氧激活化疗，实现了自扩增的协同杀伤效果。该研究为缺氧相关疾病的精准药物开发提供了结构-活性关系指导。 肿瘤缺氧微环境 | 缺氧响应释放, 协同治疗 | 前药设计, 纳米平台 Lv Furou · … · Hu Xiuli · · 2026/02/17 该研究由高分子科学河北工业大学Hu Xiuli团队完成 Biomaterials 原文链接：https://doi.org/10.1016/j.biomaterials.2026.124083 11. Pharmacokinetics-Driven Optimization of Immunotherapeutic Agents Targeting the Adenosine A2A Receptor (A2AR) and Histone Deacetylases (HDACs). 双靶点抑制剂IHCH-3185提升癌症免疫治疗效果。腺苷A2A受体拮抗剂单药疗效有限，开发具有更优药代动力学性质的双靶点药物是提升抗肿瘤活性的关键。本研究通过结构优化获得A2AR/HDAC双靶点化合物13t，其在小鼠中表现出优异的药代动力学特征并显著抑制肿瘤生长。该研究通过结合免疫刺激与直接抗增殖效应，为开发新型癌症免疫治疗药物提供了候选药物。 癌症免疫治疗 | A2AR, HDAC | 药代动力学优化 Yan Wenzhong · … · Cheng Jianjun · · 2026/02/19 该研究由药物化学上海科技大学程建军团队完成 Journal of medicinal chemistry 原文链接：https://doi.org/10.1021/acs.jmedchem.5c03481 12. Harnessing Ribonucleoprotein Granule Biology for Cancer Therapy: The Central Role of Protein Modifications. 蛋白质修饰调控核糖核蛋白颗粒在癌症治疗中的核心作用。核糖核蛋白（RNP）颗粒的异常表达驱动癌症进展，而蛋白质修饰是介导RNP与癌症相互作用的关键。本文综述了磷酸化、泛素化等修饰如何竞争性影响RNP颗粒的功能，并探讨了其在肿瘤、免疫及基质细胞中的调控机制。该研究为开发基于RNP颗粒的抗肿瘤疗法奠定了理论基础，并指出了临床转化的挑战。 癌症进展 | 核糖核蛋白(RNP), 蛋白质翻译后修饰 | 综述 Li Dengxiong · … · Feng Dechao · · 2026/02/18 该研究由泌尿肿瘤浙江省人民医院冯德超团队完成 Research (Washington, D.C.) 原文链接：https://doi.org/10.34133/research.1133 13. Eythrocyte–anti-PD1 conjugates in persons with advanced solid tumors resistant to anti-PD1/PDL1: preclinical characterization and results of a phase 1 trial 红细胞-抗PD1偶联物克服晚期实体瘤免疫治疗耐药。多数患者因免疫耐药或毒性无法从常规免疫检查点阻断中获益，亟需改变药物分布以增强疗效。研究开发了将抗PD1抗体共价连接至红细胞膜的偶联物αPD1-Ery，其在脾脏富集并重塑免疫微环境，临床试验显示客观缓解率达42.9%。该发现证明了脾脏靶向的PD1阻断策略在克服免疫治疗耐药方面的巨大潜力。 免疫治疗耐药 | PD-1, 脾脏免疫重塑 | 红细胞-抗体偶联物 Nie, Xiaoqian · … · Gao, Xiaofei · Nature Cancer · 2026/02/20 ⭐ 该研究由细胞生物学西湖大学高晓飞团队完成 原文链接：http://dx.doi.org/10.1038/s43018-026-01125-2 14. Erythrocyte–antibody conjugates to overcome immunotherapy resistance 红细胞-抗体偶联物为克服免疫治疗耐药提供新策略。克服癌症患者对免疫检查点抑制剂的耐药性是当前肿瘤免疫治疗面临的重大挑战。本文评述了利用红细胞递送抗PD-1抗体的新方法，该策略能有效重塑抗肿瘤免疫反应，并在临床试验中显示出良好的安全性。这一进展为晚期实体瘤患者提供了新的治疗选择，并展示了细胞载体在精准免疫治疗中的应用前景。 免疫治疗耐药 | PD-1 | 红细胞载体, 临床评述 Joshi, Urvashi Mitbander · Amaria, Rodabe N. · Nature Cancer · 2026/02/20 ⭐ 该研究由黑色素瘤肿瘤学MD安德森癌症中心Rodabe N Amaria团队完成 原文链接：http://dx.doi.org/10.1038/s43018-025-01105-y 15. A signature-agnostic test for differences between tumor mutation spectra reveals carcinogen and ancestry effects 签名无关测试揭示肿瘤突变谱中的致癌物和祖先效应。尽管已有多种突变签名识别工具，但仍缺乏量化不同样本组间突变暴露差异的统计方法。研究开发了AMSD方法，成功识别出多种致癌物引起的突变谱偏移以及与患者祖先相关的突变差异。该工具补充了现有的签名反卷积方法，有助于发现影响诱变的各种环境和遗传因素。 肿瘤突变谱, 遗传祖先 | 致癌物暴露, 诱变机制 | AMSD算法, 突变签名分析 Hart, Samuel F. M. · … · Harris, Kelley · · 2026/02/20 该研究由基因组学华盛顿大学Kelley Harris团队完成 Communications Biology 原文链接：http://dx.doi.org/10.1038/s42003-026-09652-5 声明：本文使用了AI进行翻译和总结