撰文丨王聪 编辑丨王多鱼 排版丨水成文 癌症患者常伴有抑郁症状 ，这通常是由于他们承受的巨大痛苦所致，这促使研究人员思考 ： 某种特定的 抗抑郁药物是否能够同时有效治疗抑郁和癌症这两种疾病？ 2026 年 1 月 5 日，海军军医大学、江南大学附属医院、中国医科大学的研究人员合作，在 Cell 子刊 Cell Reports Medicine 上发表了题为： 5-HT reuptake blockade induces pyroptosis in BRAF V600E - mutated melanomas via remodeling histone serotonylation 的研究论文。 该研究表明，一种常用的 抗抑郁药物 —— 帕罗西汀 （paroxetine hydrochloride, PH） ，竟能有效对抗 恶性 黑色素瘤 ，尤其是那些携带 BRAF V600E 突变且对靶向治疗产生耐药性的棘手病例。 黑色素瘤 患者通常面临着 双重挑战—— 由于 原发性或获得性耐药导致的治疗选择有限，以及患者普遍存 在的心理困扰，因此，亟需创新的治疗策略。 更令人振奋的是，帕罗西汀对 BRAFi/MEKi 耐 ...

编辑丨王多鱼 排版丨水成文 肿瘤免疫微环境 （ Tumor Immune Microenvironment， TIME） 对癌症的发展进程和免疫治疗响应有着 至关重要的影响。 多重免疫荧光 （mIF） 是一种强大的成像方式，可用于解析肿瘤免疫微环境 （TIME） ，但其应用受到高昂成本和较低通量的限制。 近日， 微软研究院 潘海峰 、微软研究院/华盛顿大学 王晟 等人在国际大奖学术期刊 Cell 上发表了题为： Multimodal AI generates virtual population for tumor microenvironment modeling 的研究论文。 该研究提出了 GigaTIME ，这是一个通过连接细胞形态和状态来进行大规模群体肿瘤免疫微环境建模的多 模态人工智能框架 （该工具已在 Hugging Face、GitHub 和 Microsoft Foundry 免费开源） 。 GigaTIME 学习了一种跨模态翻译器，通过在 4000 万个细胞的配对 H&E 和 mIF 数据 （涵盖 21 种蛋白 质） 上进行训练，成功实现了 从常规 H&E 病理切片到多重免疫荧光 （ mIF ...

编辑丨王多鱼 排版丨水成文 在许多 " 免疫冷肿瘤 " 中，能够识别肿瘤的特异性 T 细胞十分稀缺，而相当数量状态良好的 T 细胞却因无法识别肿瘤抗原而长期 " 旁 观 " 。与此同时，肿瘤内部又充斥免疫抑制性的巨噬细胞，使得 T 细胞难以维持持续杀伤。 如何让 " 旁观者 " 真正投入战斗，并反向利用巨噬细胞为免疫反应助力，成为破解实体瘤免疫治疗瓶颈的关键。 2025 年 12 月 10 日，上海交通大学医学院附属仁济医院、上海市妇科肿瘤重点实验室 杨帆 研究员团队联合 庄光磊 研究员和 狄文 教授，在 Nature 子刊 Nature Biomedical Engineering 上 发表了题为： A trispecific antibody engaging T cells with tumour and myeloid cells augments antitumour immunity 的研究论文。 该研究开发了一种三特异性抗体—— B7H3×CD3×PDL1 ，能够同时结合 T 细胞、肿瘤细胞和巨噬细胞，以增强抗肿瘤免疫。 该研究提出了一条突破传统的肿瘤免疫治疗的新路径——不再依赖稀有的肿瘤特异性 ...

Core Viewpoint - The article discusses the significance of Total Neoadjuvant Therapy (TNT) in the treatment of locally advanced rectal cancer (LARC) and highlights the need for a deeper understanding of the immune remodeling mechanisms involved in its efficacy [3][6]. Group 1: Treatment Strategies and Mechanisms - LARC accounts for over one-third of both incidence and mortality in colorectal cancer, which is the third most common and the second deadliest cancer globally [3]. - Recommended treatment strategies for LARC include TNT or neoadjuvant chemotherapy (nCT), with additional options like radiotherapy for cases with poor response [3]. - The immune remodeling mechanisms behind the efficacy of TNT remain unclear, necessitating further research into the tumor microenvironment (TME) changes induced by this therapy [6]. Group 2: Research Findings - A study published in Cancer Cell reveals that TNT significantly remodels the immune microenvironment in LARC, with CD8+ T cells and endothelial cells interacting as a potential key factor for clinical efficacy [4][10]. - The research utilized single-cell RNA sequencing and spatial transcriptomics to analyze pre- and post-treatment samples, showing that TNT is associated with a reduction in regulatory T cells (Treg) and an increase in IFNG+ CD8+ effector memory T cells, which may enhance complete response rates [6][7]. - The abundance of tumor-infiltrating CD8+ T cells post-TNT correlates with the enrichment of ACKR1+ endothelial cell subpopulations, which are activated by IFNγ released from CD8+ T cells, enhancing their antigen-presenting capabilities [6][7][10]. Group 3: Implications for Clinical Practice - The study provides new insights into optimizing clinical treatment strategies for rectal cancer by elucidating the complex mechanisms of immune response during neoadjuvant therapy [4][10]. - The findings suggest that the quantity of IFNG+ CD8+ T cells and peripheral blood IFNG signaling could serve as markers for response to TNT [8].

Core Viewpoint - The article discusses the role of the p53 R172H mutation in pancreatic ductal adenocarcinoma (PDAC), highlighting its contribution to creating an immunosuppressive tumor microenvironment and reducing the efficacy of immune checkpoint inhibitors (ICIs) [4][13][15]. Group 1: Background on PDAC - PDAC is a highly aggressive cancer characterized by KRAS gene activation mutations and TP53 gene alterations, with TP53 mutations leading to the loss of tumor suppressor function [2][6]. - Approximately 90% of PDAC cases have KRAS activation mutations, while around 70% exhibit changes in the TP53 tumor suppressor gene, indicating the critical role of p53 in genomic protection [7]. Group 2: Research Findings - A study published by MIT researchers reveals that the common p53 mutation, p53 R172H, occupies enhancers of immunosuppressive chemokines (e.g., Cxcl1), stimulating their expression and establishing an immunosuppressive tumor microenvironment in PDAC [3][4][11]. - The study indicates that knocking out the p53 R172H mutation enhances the efficacy of immune checkpoint inhibitors [13][15]. - Mechanistically, p53 R172H enhances Cxcl1 expression by occupying its distal enhancer, with NF-κB being a crucial cofactor for this process [12][15]. Group 3: Implications for Treatment - The findings suggest that p53 R172H promotes tumor growth by regulating cancer cell-specific gene expression programs that shape the tumor microenvironment, thereby inhibiting anti-tumor immune responses [15][16]. - In mouse models of PDAC, tumors lacking p53 R172H showed fewer T cells and higher levels of myeloid-derived suppressor cells (MDSCs), indicating a more favorable immune environment for tumor growth [15].