编辑丨王多鱼 排版丨水成文 关于 类固醇激素 影响 肿瘤生物学 的研究越来越受到关注。 2026 年 1 月 23 日，来自华中科技大学同济医学院附属同济医院 王桂华 、 胡俊波 团队 （ 黄昌胜 为论文第一作者 ） 在 Cell 子刊 Cell Metabolism 上发表了题为： Pregnenolone Promotes Immune Evasion through Blocking Endogenous Retrovirus Expression 的研究论文。 该研究发现， 类固醇代谢物 孕烯醇酮 （P5） 通过抑制 内源逆转录病毒 （ERV） 表达，促进肿瘤免疫逃逸。 这一发现不仅揭示了"神经内分泌-表 观遗传-免疫"调控新轴线，也为提升实体肿瘤免疫治疗效果提供了潜在新靶点。 在这项最新研究中，研究团队利用多种小鼠肿瘤模型，研究团队发现， 类固醇代谢物 孕烯醇酮 （P5） 会促进肿瘤进展，并降低对免疫疗法的敏感 性。在交配受限的母鼠体内，孕烯醇酮水平显著升高。 从机制上来说， 孕烯醇酮 直接与 Kap1 结合，抑制 Trim39 介导的 K750 位点的泛素化修饰，阻止其被泛素化降解，稳定并导致 K ...

Core Viewpoint - AstraZeneca's drug Imfinzi (durvalumab) has been approved by China's National Medical Products Administration (NMPA) for first-line treatment of adult patients with mismatch repair deficient (dMMR) advanced or recurrent endometrial cancer, in combination with carboplatin and paclitaxel, followed by monotherapy maintenance [1]. Group 1: Drug Approval and Mechanism - Imfinzi is a humanized PD-L1 monoclonal antibody that binds to the PD-L1 protein, blocking its interaction with PD-1 and CD80, thereby preventing tumor immune evasion and restoring suppressed immune responses [1]. - The approval in China is based on subgroup analysis results from the DUO-E Phase III trial, which is a three-arm, randomized, double-blind, placebo-controlled, multicenter study [1]. Group 2: Clinical Trial Results - In the trial, the combination of durvalumab with carboplatin and paclitaxel, followed by durvalumab monotherapy maintenance, reduced the risk of disease progression or death by 58% compared to the control group [2]. - The median progression-free survival (PFS) for the durvalumab group has not yet been reached, while the median PFS for the control group is 7.0 months [2]. Group 3: Safety Profile - The overall safety and tolerability of the durvalumab combination therapy are good, consistent with previous clinical trial results, and no new safety signals have been reported [2].

Core Viewpoint - The study identifies TRAP1 as a mitochondrial chaperone that is suppressed by cancer, leading to immune evasion, and suggests that restoring TRAP1 can reprogram tumor-associated macrophages (TAM) to enhance anti-tumor immunity, positioning the TRAP1 pathway as a promising new target for cancer immunotherapy [2][9]. Group 1 - TRAP1 is a mitochondrial HSP90 molecular chaperone that acts as a metabolic checkpoint, inhibiting oxidative respiration and limiting the suppressive function of macrophages [5]. - In the tumor microenvironment, TRAP1 expression is downregulated through the TIM4-AMPK signaling pathway, and its absence enhances immune suppressive activity while promoting tumor immune evasion [6]. - Inhibition of TRAP1 increases electron transport chain activity and raises the ratio of α-ketoglutarate to succinate, reshaping mitochondrial homeostasis and leading to enhanced immune suppression through JMJD3-mediated histone demethylation [6]. Group 2 - Targeting TIM4 and JMJD3 to restore TRAP1 can reprogram TAM, disrupt the immune evasion of the tumor microenvironment, and enhance anti-tumor immunity [7]. - The findings establish TRAP1 as a key regulatory factor integrating metabolic and epigenetic control of suppressive TAM functions, highlighting the TRAP1 pathway as a promising new target for cancer immunotherapy [9].

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].

Core Viewpoint - Recent studies reveal that taurine, a common ingredient in energy drinks, plays a significant role in leukemia progression by driving glycolysis in the tumor microenvironment, suggesting caution in its supplementation for leukemia patients [2][9]. Group 1: Taurine's Role in Leukemia - A study from the University of Rochester indicates that taurine from the tumor niche promotes glycolysis, facilitating leukemia development [2]. - The research utilized single-cell RNA sequencing to identify molecular interactions between the bone marrow microenvironment and leukemia stem cells (LSC), highlighting the importance of these interactions in leukemia progression [5]. - Taurine biosynthesis driven by cysteine dioxygenase-1 (CDO1) is limited to osteoblast lineage cells and increases during myeloid disease progression, with LSC relying on taurine transport proteins for their growth [5][6]. Group 2: Implications for Treatment - Inhibition of taurine transport proteins significantly suppresses the progression of acute myeloid leukemia (AML) in mouse models and human patient-derived cells [6]. - Elevated expression of taurine transport proteins in venetoclax-resistant AML patients suggests a potential therapeutic target, as inhibiting these proteins can enhance the efficacy of existing treatments [6]. - The study indicates that taurine uptake deficiency reduces leukemia stem cell capabilities by inhibiting mTOR activation and downstream glycolysis [6]. Group 3: Broader Research Context - Other studies have linked taurine deficiency to aging and its potential to extend healthspan in various organisms, indicating its multifaceted role in health and disease [9][11]. - Research has shown that taurine supplementation can reactivate exhausted CD8+ T cells, enhancing cancer treatment outcomes, further complicating the narrative around taurine's role in cancer [11]. - The discovery of a novel N-acetyltaurine hydrolase (PTER) suggests new avenues for obesity treatment, indicating taurine's relevance beyond oncology [14].