Pepinemab

As cancer treatment continuously evolves, immunotherapy remains at the forefront of transformative advances. At the 2025 Society for Immunotherapy of Cancer (SITC) Annual Meeting in National Harbor, Maryland, researchers from The University of Texas MD Anderson Cancer Center unveiled compelling new data that further elucidates the complex interplay between the immune system and tumor biology. These groundbreaking insights span multiple disciplines, ranging from the gut microbiome’s influence on immunotherapy response to the cutting-edge use of mRNA vaccines to convert immunologically “cold” tumors into treatable ones. Collectively, the findings presented underscore the profound impact of the tumor microenvironment and immune modulation on patient outcomes, signaling a future where cancer immunotherapy is both more personalized and effective. 癌症免疫疗法处于变革前沿。2025年癌症免疫治疗学会（SITC）年会上，德克萨斯大学MD安德森癌症中心的研究者公布了新数据，进一步阐明免疫系统与肿瘤生物学之间的复杂相互作用。突破性进展包括肠道微生物群对免疫治疗反应的影响、利用mRNA疫苗技术治疗肿瘤等。研究结果强调肿瘤微环境和免疫调节对患者结局的深远影响，预示未来癌症免疫疗法将更加个性化和有效果。 A major focus centers on the intricate role of the gut microbiome in shaping how patients respond to immune checkpoint inhibitors. Led by Dr. Jennifer Wargo, a professor of Surgical Oncology and Genomic Medicine, research reveals that microbiome diversity and the abundance of certain bacterial populations critically influence therapeutic efficacy. The team demonstrated that environmental factors—such as diet and antibiotic exposure—cause shifts in microbial composition that can either potentiate or impede immune activation against tumors. This mechanistic understanding not only provides prognostic biomarkers but also opens avenues for therapeutic manipulation through dietary interventions or synthetic microbiota transplantation, particularly for melanoma and other cancers resistant to conventional immunotherapies. Jennifer Wargo教授领导的研究揭示，微生物群多样性以及某些细菌群落丰度对治疗效果有着至关重要的影响。环境因素（例如饮食和抗生素暴露）会导致微生物组成发生变化，从而增强或抑制针对肿瘤的免疫激活。这为饮食干预或微生物群移植治疗肿瘤开辟路径，尤其在治疗黑色素瘤方面。 论文：[22Neoadjuvant pepinemab enhances immune checkpoint blockade in metastatic melanoma characterized by biomarkers of TME reprogramming including tertiary lymphoid structures]https://doi.org/10.1136/jitc-2025-SITC2025.0022 In parallel, pioneering studies into immunoprevention were highlighted by Dr. Jianjun Zhang, whose work explores leveraging immunotherapy in precancerous conditions, particularly lung cancer. By delineating the immune landscape within early diseased lung tissue, Zhang’s group discovered immunological alterations that presage tumorigenesis. This temporal mapping of immune evasion patterns enables the design of interception strategies aimed at halting malignancy before it fully develops. Harnessing such immune modulation at the pre-tumor stage holds significant promise for improving outcomes by essentially “vaccinating” high-risk individuals against cancer progression. 张建军教授重点介绍了免疫预防领域的开创性研究。研究者探索了如何利用免疫疗法治疗癌前病变，特别是肺癌。通过描绘早期病变肺组织内的免疫图谱，张教授团队发现了预示肿瘤发生的免疫学改变。这种对免疫逃逸模式的时间序列分析，可能通过设计拦截策略阻止恶性肿瘤的完全进展。在肿瘤发生前利用这种免疫调节，有望通过为高危人群“接种疫苗”来预防癌症进展，从而显著改善治疗效果。 Addressing an urgent clinical gap, Dr. Xiuning Le presented Phase III results from the HARMONi-A trial concerning EGFR-mutated non-small cell lung cancer (NSCLC) patients who have developed resistance to targeted therapies. The novel PD-1/VEGF bispecific antibody ivonescimab, when combined with chemotherapy, significantly extended overall survival compared to chemotherapy alone. This dual-targeted agent disrupts tumor immune evasion pathways while concurrently inhibiting tumor angiogenesis, a key driver of cancer growth and metastasis. Ivonescimab represents a paradigm shift toward multifaceted immunotherapeutic regimens that tackle tumor heterogeneity and resistance mechanisms concurrently. 乐秀宁教授公布了HARMONi-A III期临床试验结果，试验对象为对靶向治疗耐药的EGFR突变型非小细胞肺癌（NSCLC）患者。新型PD-1/VEGF双特异性抗体 ivonescimab 与化疗联合使用，与单独化疗相比，显著延长了患者的总生存期。这种双靶点药物能够破坏肿瘤的免疫逃逸通路，同时抑制肿瘤血管生成——肿瘤生长和转移的关键驱动因素。Ivonescimab 代表一种范式转变，即朝着多效免疫治疗方案的方向发展，同时解决肿瘤异质性和耐药机制。 论文：[1348Final overall survival analysis of HARMONi-A study comparing ivonescimab plus chemotherapy to chemotherapy alone in patients with EGFR+ NSCLC progressed on EGFR-TKI treatment] https://doi.org/10.1136/jitc-2025-SITC2025.1348 Investigations into B-cell biology are reshaping our understanding of immune-mediated tumor control. Alessandra Vaccaro’s postdoctoral research unveiled that tertiary lymphoid structures—organized aggregates of B and T cells within the tumor microenvironment—correlate with enhanced responsiveness to immunotherapy in NSCLC. This spatial organization appears to facilitate sustained anti-tumor immunity, suggesting that promoting such ectopic lymphoid structures could potentiate durable clinical responses. These insights herald a more nuanced appreciation that adaptive humoral immunity is a critical contributor to effective cancer immunotherapy. Alessandra Vaccaro的博士后研究揭示，肿瘤微环境中由B细胞和T细胞组成的三级淋巴结构与NSCLC患者对免疫疗法的反应增强相关。这种空间组织似乎有助于维持抗肿瘤免疫，提示促进此类异位淋巴结构的形成可能增强持久的临床反应。这些发现预示人们对适应性体液免疫在有效癌症免疫疗法中的关键作用有了更深刻的认识。 论文：[709A novel mouse model to investigate the impact of B cell-driven immunity in immunotherapy-treated non-small cell lung cancer] https://doi.org/10.1136/jitc-2025-SITC2025.0709 The nervous system, often overlooked in oncology, emerged as a pivotal player in modulating immune responses within tumors. Assistant professor Moran Amit’s work highlighted neural-immune crosstalk within the tumor microenvironment, demonstrating that neural signaling influences immune cell infiltration and function. Nerve-derived factors can either foster immunosuppressive conditions or promote anti-tumor immunity, thereby shaping tumor progression and therapeutic resistance. Therapeutic strategies targeting neural pathways could thus prove transformative in solid tumors like head and neck cancers. Moran Amit的研究重点关注肿瘤微环境中的神经-免疫相互作用，表明神经信号传导会影响免疫细胞的浸润和功能。神经源性因子既可以促进免疫抑制，也可以增强抗肿瘤免疫，从而影响肿瘤进展和治疗耐药性。靶向神经通路的治疗策略有望在头颈癌等实体瘤的治疗中发挥作用。 Advances in artificial intelligence (AI) are revolutionizing the predictive capabilities of imaging diagnostics in oncology. Dr. Stephane Champiat showed that radiomics combined with AI-driven image analysis can noninvasively extract biomarkers predictive of immunotherapy response and toxicity risk. By integrating imaging phenotypes with genomic data, this approach aims to achieve precision immuno-oncology, allowing clinicians to tailor treatments based on comprehensive tumor and host profiles. Such innovations promise to streamline clinical trials and accelerate drug development by identifying responders early. Stephane Champiat教授的研究表明，放射组学结合人工智能驱动的图像分析，可以无创地提取预测免疫疗法反应和毒性风险的生物标志物。通过将影像表型与基因组数据整合，该方法旨在实现精准肿瘤免疫，使临床医生能够根据全面的肿瘤和宿主特征来制定个性化治疗方案。此类创新有望通过早期识别有效患者来简化临床试验流程并加速药物研发。 Further breakthroughs were introduced by Dr. Adam Grippin’s exploration of mRNA vaccine technology in oncology. Traditionally applied against infectious diseases, mRNA vaccines were shown to activate immune responses against tumors historically deemed immunologically “cold,” which lack adequate T cell infiltration. The vaccines function by stimulating antigen-presenting cells and inducing PD-L1 expression on cancer cells, rendering them susceptible to immune checkpoint blockade. This synergistic mechanism has the potential to broaden immunotherapy’s applicability across a spectrum of tumor types refractory to current treatments. Adam Grippin教授对mRNA疫苗技术在肿瘤领域的探索取得突破。研究表明，mRNA疫苗能够激活针对以往被认为是免疫“冷”肿瘤（即缺乏足够T细胞浸润的肿瘤）的免疫反应。疫苗作用机制是通过刺激抗原呈递细胞并诱导癌细胞表达PD-L1，从而使癌细胞对免疫检查点阻断疗法更加敏感。 论文：[419SARS-CoV-2 mRNA vaccines sensitize immunologically ‘cold’ tumors to immune checkpoint blockade] https://doi.org/10.1136/jitc-2025-SITC2025.0419 On the molecular genetics front, Dr. Dustin McCurry uncovered a novel immune evasion pathway in leukemia linked to oncogenic mutations in ASXL1. Utilizing CRISPR gene editing, the team demonstrated that these mutations alter immune marker presentation on cancer cells, allowing them to escape immune surveillance. Correcting these mutations restored immune visibility, unveiling promising genetic targets for re-sensitizing resistant leukemias to immunotherapy. This study illuminates how mutational landscapes intricately intersect with immune dynamics in hematologic malignancies. Dustin McCurry教授发现了白血病中一种与ASXL1致癌突变相关的新型免疫逃逸通路。利用 CRISPR基因编辑技术，团队证实这些突变会改变癌细胞表面的免疫标志物表达，使其逃避免疫监视。纠正这些突变后免疫反应得以恢复，针对这些靶点的免疫疗法有望重新激活耐药白血病的免疫反应。研究阐明了血液系统恶性肿瘤中突变图谱与免疫动力学之间错综复杂的相互作用。 论文：[1228Immune escape through oncogene-mediated editing of the HLA-ligandome] https://doi.org/10.1136/jitc-2025-SITC2025.1228 The immunomodulatory effects of radiation therapy were rigorously examined by Dr. Robert Saddawi-Konefka, who investigated how tumor-directed, lymphatic-sparing radiation reprograms migratory dendritic cells responsible for priming anti-tumor T cells. Their sequencing protocol, applying focused radiotherapy followed by PD-1 blockade, induced potent tumor rejection and durable immunologic memory in preclinical models. This approach leverages the immune-stimulatory properties of radiation while preserving lymphatic function critical for immune activation, advancing combined modality strategies in cancer treatment. Robert Saddawi-Konefka教授对放射疗法的免疫调节作用进行了深入研究。他研究了肿瘤靶向、淋巴系统保护性放射疗法如何重编程负责启动抗肿瘤T细胞的迁移性树突状细胞。他们提出的序贯治疗方案，即先进行聚焦放射治疗，再进行PD-1阻断治疗，在临床前模型中诱导了强效的肿瘤排斥反应和持久的免疫记忆。这种方法既利用了放射疗法的免疫刺激特性，同时保留了对免疫激活至关重要的淋巴功能。 论文：[676Lymphatic-sparing immunoradiotherapy reprograms migratory dendritic cells to drive tumor rejection via the sentinel lymph node] https://doi.org/10.1136/jitc-2025-SITC2025.0676 Taken together, these diverse lines of investigation provide a detailed framework for understanding how immune system engagement can be optimized across multiple cancer types and stages. The integration of microbiome science, cutting-edge imaging analytics, neural immunology, genetic editing, and vaccine technology marks a new era where each dimension of tumor biology can be precisely manipulated. As these research efforts continue to mature into clinical applications, the promise of personalized, durable, and broadly effective cancer immunotherapies edges closer to reality. The 2025 SITC Annual Meeting showcased that the future of oncology will be shaped not only by targeting tumors directly but by fundamentally reprogramming the immune landscape in innovative and multi-pronged ways. 微生物组学、前沿成像分析、神经免疫学、基因编辑和疫苗技术的整合标志着一个新时代的到来，在这个时代，肿瘤生物学的各个维度都能够被精准操控。随着这些研究成果不断成熟并最终应用于临床，个性化、持久且广谱有效的癌症免疫疗法会逐步成为现实。肿瘤学的未来不仅在于直接靶向肿瘤，更在于以多种创新方式从根本上重塑免疫治疗格局。 Web References: MD Anderson Cancer Center: https://www.mdanderson.org/ 2025 Society for Immunotherapy of Cancer Annual Meeting: https://www.sitcancer.org/2025/schedule/sitc25-annualmeeting ESMO 2025 mRNA vaccine study: https://www.mdanderson.org/newsroom/research-newsroom/-esmo-2025–mrna-based-covid-vaccines-generate-improved-response.h00-159780390.html Nature publication (mRNA vaccines): https://www.nature.com/articles/s41586-025-09655-y Source：https://bioengineer.org/md-anderson-experts-highlight-breakthrough-immunotherapy-advances-at-2025-sitc-annual-meeting/ Translate by WuTong.