自2011年引入癌症治疗以来，免疫检查点抑制剂(ICIs)被誉为突破性的癌症疗法。免疫检查点蛋白在T细 胞表面表达，作为抑制T细胞过度激活的调节因子。然而，该公司周一指出的临床前和临床研究表明， ICIs缺乏免疫细胞共刺激活性，从而降低了其抗肿瘤疗效。 本文源自：智通财经网 智通财经获悉，周一，HCW Biologics(HCWB.US)暴涨近70%，报5.81美元。消息面上，该公司报告 称，其科学家已开发出第二代基于帕博利珠单抗的免疫治疗药物，针对实体肿瘤，特别是胰腺癌和卵巢 癌，采用其新颖的专有TRBC产品发现和开发平台技术。 ...

自2011年引入癌症治疗以来，免疫检查点抑制剂(ICIs)被誉为突破性的癌症疗法。免疫检查点蛋白在T细 胞表面表达，作为抑制T细胞过度激活的调节因子。然而，该公司周一指出的临床前和临床研究表明， ICIs缺乏免疫细胞共刺激活性，从而降低了其抗肿瘤疗效。 智通财经APP获悉，周一，HCW Biologics(HCWB.US)暴涨近70%，报5.81美元。消息面上，该公司报 告称，其科学家已开发出第二代基于帕博利珠单抗的免疫治疗药物，针对实体肿瘤，特别是胰腺癌和卵 巢癌，采用其新颖的专有TRBC产品发现和开发平台技术。 ...

自2011年引入癌症治疗以来，免疫检查点抑制剂(ICIs)被誉为突破性的癌症疗法。免疫检查点蛋白在T细 胞表面表达，作为抑制T细胞过度激活的调节因子。然而，该公司周一指出的临床前和临床研究表明， ICIs缺乏免疫细胞共刺激活性，从而降低了其抗肿瘤疗效。 周一，HCW Biologics(HCWB.US)暴涨近70%，报5.81美元。消息面上，该公司报告称，其科学家已开 发出第二代基于帕博利珠单抗的免疫治疗药物，针对实体肿瘤，特别是胰腺癌和卵巢癌，采用其新颖的 专有TRBC产品发现和开发平台技术。 ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 乳酸 （ lactic acid，LA ） 是肿瘤微环境 （TME） 中最丰富的代谢产物之一。肿瘤微环境中积累的乳酸，同时通过损害 CD8⁺ T 细胞的细胞毒性作用和促进调 节性 T 细胞 （ T reg ） 的免疫抑制功能， 建立双重免疫抑制屏障， 来促进肿瘤生长，增强肿瘤免疫逃逸，但其潜在机制目前仍不十分清楚。 2025 年 8 月 22 日， 上海交通大学医学院 童雪梅 教授、复旦大学基础医学院青年研究员 卢颖 、上海交通大学医学院 李斌 教授 、上海交通大学医学院附属第九人民医院 贾仁兵 主任医师等，在 Nature 子刊 Nature Metabolism 上发表了题为 ： Targeting MondoA–TXNIP restores antitumour immunity in lactic-acid-induced immunosuppressive microenvironment 的研究论文。 该研究发现， 乳酸 激活了 MondoA-TXNIP 通路，抑制了 CD8⁺ T 细反应，并增强了 T reg 细胞功能，从而促进了肿瘤的生长和免疫逃逸。而抑 ...

Core Viewpoint - The research led by Professor Tao Wei from Harvard Medical School demonstrates that IL-10-mRNA nanoparticles can significantly enhance cancer immunotherapy effectiveness and induce lasting anti-tumor immune memory, effectively preventing cancer recurrence [2][3][5]. Group 1: Research Findings - The study confirms that intravenous injection of IL-10-mRNA nanoparticles triggers strong immune surveillance in various preclinical tumor models while reducing systemic toxicity [4]. - IL-10-mRNA nanoparticles maintain local IL-10 production, promoting extensive infiltration and proliferation of cytotoxic T cells, activation and maturation of dendritic cells, and upregulation of MHC-I molecules in immunosuppressive early-stage liver cancer [5]. - In a model of advanced liver cancer, the combination of IL-10-mRNA nanoparticles and immune checkpoint blockade therapy achieved complete tumor clearance in 43% of mice, extending median survival sixfold compared to the immune checkpoint blockade alone, and providing 100% protection against tumor reattack [5][7]. Group 2: Implications for Treatment - The strategy of intravenous injection of IL-10-mRNA nanoparticles is expected to overcome the limitations faced by recombinant IL-10 in clinical trials for various immunosuppressive tumors [7].

Core Viewpoint - The study highlights the role of DNASE1L3-expressing dendritic cells in enhancing CD8+ T cell function and improving the efficacy of anti-PD-1/PD-L1 therapies by degrading neutrophil extracellular traps (NETs) [2][3][5]. Group 1: Research Findings - The expression of DNASE1L3 in tumor-infiltrating dendritic cells is positively correlated with better prognosis in cancer patients undergoing anti-PD-1/PD-L1 therapy [5]. - Conditional knockout of DNASE1L3 in dendritic cells leads to accelerated tumor growth and reduced efficacy of anti-PD-L1 therapy due to impaired CD8+ T cell infiltration and function [5]. - Exogenous supplementation of DNASE1L3 enhances CD8+ T cell infiltration into the tumor microenvironment, reduces T cell exhaustion, significantly inhibits tumor growth, and improves responses to anti-PD-L1 therapy [5]. Group 2: Mechanistic Insights - DNASE1L3+ dendritic cells maintain a cytotoxic CD8+ T cell hub by degrading NETs, which inhibit the spatial distribution of CD8+ T cells within tumors [5][8]. - The absence of DNASE1L3 in dendritic cells promotes tumor growth through CD8+ T cell dysfunction [5][8]. Group 3: Implications for Therapy - DNASE1L3 is identified as a promising new target for improving the effectiveness of anti-PD-1/PD-L1 therapies [8].

Core Viewpoint - The study reveals that targeting dihydroorotate dehydrogenase (DHODH) to inhibit macropinocytosis in tumor cells is a potential method to reverse immunosuppression and improve cancer immunotherapy [8]. Group 1: Key Findings - High-throughput screening identified DHODH as essential for cancer cell macropinocytosis [6]. - DHODH maintains the O-GlcNAc glycosylation modification and membrane localization of neuropilin-1 (NRP1), promoting macropinocytosis [6]. - Macropinocytosis increases the acetylation of transcription factor CIITA, leading to the suppression of major histocompatibility complex class II (MHC II) expression, thereby facilitating immune evasion [6]. Group 2: Implications for Immunotherapy - Inhibition of DHODH in cancer cells significantly enhances immune cell infiltration and activates anti-tumor immune responses, overcoming resistance to anti-PD-1 therapy [5][6]. - High expression levels of DHODH and NRP1 in human breast and lung cancer tissues correlate with poor patient prognosis [5].

该研究揭示， 在人类演化过程中新出现的、对大脑发育和认知功能至关重要的人类特有新基因，可能同时具有促癌作用 ，在此基础上，研究团队开发了 mRNA 癌症疫苗， 有效激发了 抗肿瘤免疫反应并显著抑制了肿瘤生长。这项研究连接了演化基因组学与癌症医学，为癌症治疗提供了新思路。 撰文丨王聪 编辑丨王多鱼 排版丨水成文 从头起源基因 （ de novo gene ） ，是直接从非编码区域演化而 来的新基因，其缺乏先前存在的"母基因"作为其 蛋白质序列、结构和功能的模板。在人类中， 这种从头起源的新基因，在塑造人类特有的性状以及疾病易感性方面可能具有潜在作用。然而，由于这些的内在特性 （序列 较短、表达受限且表达水平较低、频 繁出现在重复基因组区域以及跨物种保守性有限等 ） ，使得基因注释变得负责，限制了我们对其进行系统性研究。 近日，中国科学院遗传与发育生物学研究所 李川昀 团队与北京大学 程强 团队合作，在 Cell 子刊 Cell Genomics 上 发表了题为： Oncogenic roles of young human de novo genes and their potential as neoanti ...

Core Viewpoint - Cancer-associated fibroblasts (CAF) play a critical role in supporting tumor growth and metastasis through extracellular matrix remodeling, paracrine signaling, and immune suppression, which limits the efficacy of immune checkpoint blockade (ICB) therapies [2][3]. Group 1 - The study published by researchers from the University of Chicago in the journal Nature reveals that NNMT promotes the recruitment of myeloid-derived suppressor cells (MDSC) into tumors via CAF, leading to the formation of an immunosuppressive tumor microenvironment (TME) [4]. - The research demonstrates that NNMT is expressed in all CAF subtypes and induces H3K27me3 hypomethylation, which facilitates the secretion of complement proteins that recruit MDSC into the tumor [7]. - The team developed a potent and specific NNMT inhibitor (NNMTi) that reduced tumor burden and metastasis in various mouse tumor models by decreasing CAF-mediated MDSC recruitment and reactivating CD8+ T cell activation, thereby restoring the efficacy of ICB therapy [9]. Group 2 - Overall, the study indicates that NNMT is a key regulatory factor of immunosuppression in the tumor microenvironment and represents a promising new target for alleviating immune suppression and enhancing cancer immunotherapy effectiveness [11].

Core Viewpoint - The article discusses the limitations of current cancer therapies based on secreted proteins and highlights a new research study that identifies potential immunotherapy targets through a cancer immunology data platform [2][3][12]. Group 1: Research Findings - The study developed a cancer immunology data platform called CIDE, which integrates 90 multi-omics datasets covering 8,575 tumor samples across 17 types of solid tumors [8][12]. - CIDE systematically identifies genes related to immunotherapy outcomes and has revealed secreted proteins such as AOAH, CR1L, COLQ, and ADAMTS7 as new immune checkpoint blockade (ICB) regulators [9][15]. - AOAH enhances immunotherapy through dual mechanisms: increasing T cell receptor (TCR) sensitivity to weak antigens and removing inhibitory lipids that suppress dendritic cell function [10][15]. Group 2: Implications for Cancer Treatment - The findings suggest that the identified secreted proteins could serve as precise targets for a new generation of immunotherapies, overcoming the limitations of traditional therapies like IL-2 and VEGF inhibitors, which have low response rates and unstable efficacy [17]. - AOAH's validation across multiple tumor models indicates its potential as a broad-spectrum immune enhancer [18]. Group 3: Future Directions - The research aims to expand the functional map of secreted proteins, particularly focusing on the 61% of previously unreported proteins related to cancer, to discover new molecules that regulate the immune microenvironment [20]. - There is a focus on targeting lipid-immune interactions based on AOAH-related lipid metabolism pathways for developing small molecule drugs or combination therapies [20]. - The study emphasizes the need for clinical translation of molecules like AOAH as biomarkers or therapeutic targets through preclinical and clinical trials [20].