撰文丨王聪 编辑丨王多鱼 排版丨水成文 利用免疫系统靶向和清除肿瘤细胞的癌症免疫疗法，已经彻底改变了癌症治疗格局。其中， 免疫检查点阻断 （ICB） 疗法，通过抑制 T 细胞活化的负调控因子来 增强抗肿瘤免疫反应，在部分癌症患者中取得了显著成功。然而，仍有相当大比例的癌症患者对此类治疗无应答，这凸显了理解影响 ICB 疗效因素的迫切性。 肠道微生物群 由驻留在胃肠道的数以万亿计的微生物组成，已成为影响免疫功能和癌症免疫疗法应答的关键决定因素，多项研究已证明，肠道微生物群的组成与 临床治疗响应存在关联。然而，关于肠道共生细菌如何影响 ICB 疗效的机制性理解仍然不清楚。 2026 年 1 月 14 日， 纽约大学医学院 Dan R. Littman 团队在国际顶尖学术期刊 Nature 上发表了题为： Microbiota-induced T cell plasticity enables immune-mediated tumour control 的研究论文。 该研究表明， 肠道微生物群诱导的 T 细胞可塑性，使免疫介导的肿瘤控制成为可能。因此 ， 靶向调控肠道微生物群可作为扩大免疫检查点阻断 （ICB） ...

撰文丨王聪 编辑丨王多鱼 排版丨水成文 卵巢癌 （ Ovarian Cancer， OC） 是致死率最高的妇科恶性肿瘤，2022 年全球新增病例 324938 例，死亡病例 206834 例。以铂类药物为基础的化疗联合紫 杉醇 （可选择加用或不加用贝伐珠单抗） ；近年来，还会在此基础上联合维持治疗的 PARP 抑制剂和/或贝伐珠单抗，是晚期卵巢癌的主要治疗选择。 尽管当前的卵巢癌一线治疗的应答率为 75% - 80%，但大多数患者在 18 个月内仍会出现癌症复发。对于 铂耐药卵巢癌 ，标准的非铂类化疗疗效有限，仅有 ≤15% 的患者出现客观缓解，中位无进展生存期 （PFS） 在 3 - 4 个月之间 。因此， 临床上迫切需要新型安全有效的抗血管生成药物用于铂耐药卵巢癌的治 疗。 2026 年 1 月 9 日，中国医学科学院肿瘤医院 吴令英 教授 、 山东第一医科大学附属肿瘤医院（山东省肿瘤医院） 李清水 教授等，在 Nature 子刊 Nature Cancer 上发表了题为： Suvemcitug plus chemotherapy in women with platinum-resistant recu ...

Core Viewpoint - Obesity is a significant global public health crisis linked to various chronic diseases, characterized by persistent low-grade inflammation that exacerbates disease progression [6][7]. Group 1: Research Findings - A study published in Science reveals that obesity reshapes macrophage nucleotide metabolism, leading to hyperactivation of the NLRP3 inflammasome and uncontrolled inflammation, accelerating disease progression [3][4]. - The study identifies SAMHD1 as an intrinsic inhibitor in macrophages that can suppress NLRP3 inflammasome activation across species from fish to humans [3]. Group 2: Mechanisms of Inflammation - The NLRP3 inflammasome acts as an "alarm" in the immune system, activated by tissue damage or stress, producing pro-inflammatory cytokines like IL-1β, which, in obesity, disrupt insulin signaling and accelerate metabolic diseases [9]. - Obese individuals exhibit an increased amount of oxidized mitochondrial DNA (ox-mtDNA) in their immune cells, which activates the NLRP3 inflammasome [11][12]. Group 3: Role of SAMHD1 - SAMHD1 is crucial for maintaining nucleotide balance in cells, and obesity leads to its phosphorylation and functional impairment, resulting in excessive NLRP3 inflammasome activation [14]. - The absence of functional SAMHD1 in animal models leads to NLRP3 hyperactivation, indicating its role as a regulatory mechanism against inflammation [14]. Group 4: Metabolic Reprogramming - Obesity alters the metabolic pathways in immune cells, allowing excess dNTPs to enter mitochondria via nucleotide transport proteins, bypassing normal synthesis pathways and leading to uncontrolled mtDNA synthesis [16]. - Blocking dNTP transport into mitochondria can reverse obesity-related inflammation, suggesting a potential therapeutic direction [16]. Group 5: Clinical Implications - Mice lacking SAMHD1 exhibit typical metabolic abnormalities after a high-fat diet, and blocking dNTP transport alleviates these symptoms [18]. - The study's findings indicate that targeting mitochondrial dNTP transport could lead to new therapies for chronic inflammation and metabolic diseases associated with obesity, offering a more precise approach than traditional immune response suppression methods [18].

Core Insights - The article discusses the challenges in clinical trials targeting cancer-associated fibroblasts (CAFs), which are crucial tumor-promoting factors, due to their inherent functional plasticity and the opaque regulatory circuits behind their heterogeneous phenotypes [2] Group 1: Research Findings - A study published in Cancer Cell identified ADAM12 as a fibroblast checkpoint that impedes anti-tumor immunity, with its deletion delaying tumor progression and making tumors more sensitive to immunotherapy [3] - The research team developed a systematic screening method based on complementary CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) to screen patient-derived fibroblasts [5] - The study found that the I-type interferon (IFN-I) response program is a primary antagonistic axis against TGF-β-driven tumor-promoting myofibroblast activation, with ADAM12 mediating this relationship [5] Group 2: Implications for Treatment - Deletion of ADAM12 triggers the IFN-I response program, reconfiguring the myofibroblast population into progenitor-like states, revitalizing T-cell-based immune responses, and inducing tumor rejection in various mouse models [5] - The research positions ADAM12 as a potential target for therapeutic interventions, paving the way for future treatment strategies [5][7] - The study emphasizes the conversion of TGF-β dependent myCAF programs into IFN-I response states to exert anti-tumor activity, enhancing T-cell infiltration and sensitivity to immunotherapy [7]

Core Viewpoint - The article discusses the first direct observation of the Migdal effect, a significant breakthrough in physics that could aid in the exploration of light dark matter and address a long-standing theoretical gap in the field [3][4]. Group 1: Research Findings - The research team successfully observed the Migdal effect by bombarding gas molecules in a detector with neutrons, distinguishing the "co-vertex" images of simultaneous nuclear and electronic events from complex background noise [6]. - This discovery marks the end of an 80-year wait in the physics community for direct evidence of the Migdal effect, solidifying its theoretical foundation [4][10]. Group 2: Implications - The direct observation of the Migdal effect fills a long-existing experimental validation gap and brings humanity closer to unraveling the mysteries of the universe, particularly regarding dark matter [10].

Core Viewpoint - The article discusses a significant breakthrough in the construction of lateral heterostructures in two-dimensional perovskite materials, highlighting the successful controlled patterning of mosaic lateral heterojunctions in thin-layer two-dimensional perovskite single crystals [4]. Group 1 - The research addresses the limitations of existing polycrystalline thin-film structures, which suffer from defects and poor ionic migration behavior, thereby hindering carrier transport efficiency and device performance [3]. - The study presents a method to create size-controllable square holes in two-dimensional perovskite, enabling the construction of large-area continuous lateral heterostructures [6]. - The team successfully synthesized a mosaic lateral heterostructure capable of emitting multiple colors, providing a versatile material platform for developing complex integrated light-emitting devices [6]. Group 2 - The lateral heterostructures are significant for exploring exotic physical phenomena, developing new devices, and achieving miniaturization of equipment [5]. - The research utilizes a patterned template growth technique, which offers a feasible solution for large-area patterning of heterostructures [5]. - The synthesis method provides new insights into the structural characteristics of perovskites and enhances the understanding of their properties [6].

Core Viewpoint - The article discusses the Warburg effect, highlighting how cancer cells exhibit increased glycolysis even in the presence of oxygen, leading to enhanced lactate production and cancer progression. Recent research has uncovered the molecular mechanisms behind this phenomenon, specifically focusing on the role of lactate in activating the ERK signaling pathway through a lactylation-phosphorylation loop involving the enzyme GCN5 [2][3][5][7]. Group 1 - The Warburg effect describes the phenomenon where cancer cells maintain high levels of glycolysis despite sufficient oxygen, which is contrary to normal cellular metabolism [2]. - A recent study published in Nature Chemical Biology reveals that lactate promotes tumor progression by inducing lactylation of the ERK protein, enhancing the RAS-ERK signaling pathway [3][5]. - The study identifies GCN5 as the lactyltransferase responsible for ERK lactylation, which is activated by ERK phosphorylation, creating a positive feedback loop that amplifies lactate-driven cancer progression [5][7]. Group 2 - The research demonstrates that lactate-induced ERK lactylation weakens its interaction with MEK, promoting ERK dimerization and activation, which further drives cancer development [5][7]. - A cell-penetrating peptide was developed to specifically inhibit ERK lactylation, showing potential in suppressing tumor growth in KRAS mutant cancer models [5][7].

Core Insights - On January 14, 2026, a total of 25 research papers were published in the prestigious journal Nature, with 11 of them authored by Chinese scholars, highlighting the significant contribution of Chinese researchers to global scientific advancements [3][5][7][8][10][12][13][15][17][19]. Group 1: Research Contributions - The paper titled "Mosaic lateral heterostructures in two-dimensional perovskite" was co-authored by Zhang Shuchen from the University of Science and Technology of China, Dou Letian from Purdue University, and Yu Yi from ShanghaiTech University [3]. - The research "Exciplex-enabled high-efficiency, fully stretchable OLEDs" was authored by Zhou Huanyu and Zhang Danzhen from Seoul National University [5]. - The study "Direct observation of the Migdal effect induced by neutron bombardment" featured Yi Difan as the first author, with contributions from Zheng Yangheng and others from various Chinese universities [7][8]. - The paper "3D-printed low-voltage-driven ciliary hydrogel microactuators" was co-authored by Liu Zemin from the Max Planck Institute for Intelligent Systems and the Swiss Federal Institute of Technology in Zurich [10]. - The research "Trapping of single atoms in metasurface optical tweezer arrays" was co-authored by Yu Nanfang from Columbia University [12]. - The study "The Ubiquitin Ligase KLHL6 Drives Resistance to CD8 T Cell Dysfunction" was led by Li Guideng from the Chinese Academy of Medical Sciences [13]. - The paper "Language model-guided anticipation and discovery of mammalian metabolites" was co-authored by Qiang Hantao from Princeton University and Wang Fei from the University of Alberta [15]. - The research titled "Artificial intelligence tools expand scientists' impact but contract science's focus" was co-authored by Li Yong and Xu Fengli from Tsinghua University [17]. - The study "Sub-zero Celsius elastocaloric cooling via low-transition-temperature alloys" was led by Sun Qingping from the Hong Kong University of Science and Technology [19].

Core Viewpoint - The research published by Professor Ren Wenkai's team from South China Agricultural University indicates that Lactobacillus reuteri and its metabolite L-theanine enhance the catabolism of branched-chain amino acids (BCAA), providing a potential therapeutic pathway for metabolic disorders associated with elevated BCAA levels [2][6]. Group 1 - The study reveals that gut microbiota can regulate circulating BCAA levels through direct conversion, and it uncovers an indirect mechanism by which gut microbiota influences host BCAA metabolism [4]. - The research team compared germ-free mice and pigs with wild-type counterparts, finding that Lactobacillus reuteri and L-theanine are associated with enhanced BCAA catabolism [5]. - Experiments on pig cell lines demonstrated that L-theanine increases the expression of branched-chain amino transferase (BCAT), which is involved in BCAA catabolism, by promoting BCAT2 mRNA expression and stabilizing the BCAT2 protein [5]. Group 2 - Overall, the study provides a potential pathway for developing therapies targeting metabolic disorders related to elevated BCAA levels [6].

Core Viewpoint - The article emphasizes the significant role of the dynamic interaction between tumor cells and the host in the pathogenesis of cancer cachexia, a syndrome affecting approximately 50%-80% of cancer patients, with varying incidence rates across different malignancies [2][4]. Group 1: Overview of Cancer Cachexia - Cancer cachexia is characterized by systemic inflammation, weight loss, and muscle and fat tissue atrophy, primarily due to increased energy expenditure, hypermetabolism, and anorexia [4]. - Clinical criteria for considering cancer cachexia risk include weight loss of ≥5% within six months, BMI <20 kg/m² with weight loss of ≥2%, and weight loss of ≥2% in sarcopenic patients [4]. - The syndrome significantly impacts patients' quality of life, exacerbates treatment-related toxicities, and increases mortality rates by 20%-30% [4]. Group 2: Mechanisms and Interactions - The review discusses the systemic metabolic syndrome involving multiple tissues and organs, including skeletal muscle, fat, and liver, and how tumors influence distant organs through neural, blood, and lymphatic networks [5][19]. - It posits that catabolic metabolism activation and anabolic metabolism suppression are key features in cancer cachexia, leading to inflammatory responses that disrupt energy homeostasis [5][23]. - The interplay between metabolic reprogramming and inflammatory responses creates a vicious cycle, with immune and stromal cells releasing inflammatory mediators that further disturb systemic metabolism [23][26]. Group 3: Recent Advances and Therapeutic Strategies - Recent studies highlight innovative therapeutic strategies aimed at alleviating cancer cachexia, including the approval of Anamorelin, a ghrelin receptor agonist, which has shown promise in increasing muscle mass and weight [25]. - Targeting specific inflammatory factors, such as GDF15 with Ponsegromab, has demonstrated potential in improving weight and activity levels in early clinical trials [25]. - Metabolic interventions, including supplementation with specific amino acid derivatives and ω-3 fatty acids, have been shown to alleviate symptoms of cancer cachexia [26]. Group 4: Future Research Directions - The complexity of cancer cachexia mechanisms necessitates further research to identify new therapeutic targets, integrating immunology and metabolomics approaches [26]. - The need for more comprehensive studies using optimal animal models to simulate cachexia states is emphasized to enhance understanding of the syndrome's progression [26].