Core Viewpoint - The 2025 Nobel Prize in Physiology or Medicine was awarded to two American scientists, Mary E. Brencoe and Fred Ramsdell, along with Japanese scientist Shimon Sakaguchi, for their discoveries in the field of peripheral immune tolerance, which is crucial for preventing autoimmune diseases [1][6]. Group 1: Immune System and Autoimmune Diseases - The immune system functions as a "health guardian," responsible for combating pathogens and maintaining internal balance by eliminating mutated or dead cells [6]. - Autoimmune diseases occur when the immune system mistakenly attacks normal cells, leading to conditions such as rheumatoid arthritis and systemic lupus erythematosus [6]. - The key to why not everyone develops severe autoimmune diseases lies in the immune system's "recognition correction" mechanism, known as immune tolerance [6]. Group 2: Mechanisms of Immune Tolerance - Immune tolerance is divided into "central tolerance," which eliminates immune cells that recognize self-antigens during development, and "peripheral tolerance," which acts as a "brake system" to protect self-tissues while eliminating threats [6][7]. - The Nobel Prize-winning research focused on the "brake system," identifying regulatory T cells (Treg) as crucial components in peripheral tolerance [6][8]. Group 3: Clinical Applications and Challenges - The findings open new avenues for treating autoimmune diseases, organ transplantation, and cancer therapy [8][9]. - For autoimmune diseases, low-dose interleukin-2 (IL-2) can enhance Treg cells to restore immune balance [8]. - In organ transplantation, increasing Treg activity can reduce rejection responses, improving graft survival [9]. - In cancer treatment, strategies to weaken local Treg cells are necessary to allow immune cells to attack tumors effectively [9]. - Current therapies face challenges in precision and safety, with ongoing research needed to develop effective clinical applications [10].

Core Viewpoint - The article discusses a novel therapeutic approach targeting pathogenic T cells in autoimmune diseases, focusing on the mechanism of LAG-3 and T Cell Receptor (TCR) interaction, which offers a new strategy for treatment [4][10]. Group 1: Mechanism of Action - Autoimmune diseases are caused by overactive immune responses leading to tissue damage, with T cells playing a crucial role in diseases like type 1 diabetes and rheumatoid arthritis [2][3]. - LAG-3, an inhibitory immune checkpoint receptor, is regulated by its classical ligand MHC-II, and its activation is dependent on the spatial proximity to TCR, which is essential for effective suppression of CD4+ T cells [4][5][7]. - The study reveals that LAG-3's optimal function requires not just interaction with MHC-II but also the formation of a spatial proximity with TCR, which is a key molecular mechanism for T cell inhibition [7][8]. Group 2: Therapeutic Development - The research team developed a bispecific T cell silencer (BiTS) that targets the interaction between LAG-3 and TCR, allowing for selective modulation of pathogenic T cells while preserving beneficial T cell functions [5][10]. - This innovative approach has shown significant therapeutic effects in various animal models of autoimmune diseases, indicating its potential for treating conditions like refractory multiple sclerosis and rheumatoid arthritis [5][10]. - The study provides a unique opportunity for precise intervention in T cell-driven autoimmune diseases, addressing the current lack of safe and effective therapies [10].

Group 1: New Pain Relief Drug - A new experimental pain relief drug, SBI-810, has been developed that provides effective pain relief for both acute and chronic pain, targeting the neurotensin receptor-1 (NTSR1) and activating specific pain signals while avoiding addiction-related side effects [3][6] - The research highlights the potential of NTSR1 biased allosteric modulators as a promising non-addictive pain management strategy, addressing both peripheral and central nervous system mechanisms [6] Group 2: Love Switch in the Brain - A study identified a specific group of neurons in the medial prefrontal cortex (mPFC) that regulates "romantic interest," integrating hormonal states and social cues to control social behaviors [8][11] - This research provides a theoretical basis and potential intervention targets for understanding gender-related social disorders, revealing a "love switch" in the brain that is dynamically regulated by hormonal changes [11] Group 3: Antidepressants Enhancing Cancer Immunotherapy - Research indicates that the serotonin transporter (SERT) acts as an immune checkpoint, and selective serotonin reuptake inhibitors (SSRIs) can significantly enhance T cell anti-tumor immunity, inhibiting tumor growth in various cancer models [13][17] - SSRIs, widely used for depression, show promise as candidates for cancer immunotherapy, potentially offering a more accessible treatment option compared to developing new cancer drugs [17] Group 4: Evidence for Acquired Inheritance Theory - A study provides direct evidence for the theory of acquired inheritance in rice, demonstrating that cold tolerance traits can be inherited through DNA methylation, challenging traditional Darwinian evolution frameworks [19][24] - The research reveals that environmental-induced epigenetic mutations can be stably inherited, offering new insights into adaptive evolution and innovative strategies for crop breeding [24] Group 5: Near-Infrared Vision Contact Lenses - A team developed wearable near-infrared (NIR) upconversion contact lenses that enable humans to perceive NIR spatial and color information, showcasing the potential of polymer materials in non-invasive visual enhancements [26][29] - This innovation could have broad applications in medical, information processing, and visual assistance technologies, potentially offering new solutions for visual impairments such as color blindness [29]

Core Viewpoint - Lung cancer remains the leading cause of cancer-related deaths globally, primarily due to late-stage diagnosis, emphasizing the critical need for early detection and intervention [1][11]. Group 1: Importance of Early Detection - Early diagnosis and intervention are crucial, with low-dose spiral CT screening significantly reducing lung cancer mortality rates [1]. - Understanding the molecular mechanisms of early lung cancer is vital for precise screening, diagnosis, prevention, and treatment [1]. Group 2: Challenges in Research - The study of early cancer development, particularly lung adenocarcinoma (LUAD), faces significant challenges due to the scarcity of precursor lesion specimens [1]. - Atypical adenomatous hyperplasia (AAH) is recognized as the only precursor lesion for lung adenocarcinoma, with potential progression to non-invasive adenocarcinoma in situ (AIS) and invasive adenocarcinoma (IAC) [1]. Group 3: Recent Research Findings - A recent study published in Cancer Cell identified TIM-3 as a potential target for lung cancer "precancer interception" through spatial and multiomics analysis of human and mouse lung adenocarcinoma precursors [2]. - The research revealed a significant upregulation of TIM-3 in myeloid immune cells during the precancerous stage, suggesting its role in immune regulation within the tumor microenvironment [6][7]. Group 4: Immune Response Dynamics - The transition from precancerous lesions to invasive cancer is associated with changes in macrophage polarization and T cell functionality, indicating a shift from innate to adaptive immune responses [6]. - The study identified 818 spatial features related to immune checkpoint TIM-3, highlighting its central regulatory role in early tumor evolution [6]. Group 5: Therapeutic Implications - Blocking TIM-3 demonstrated significant potential for "precancer interception," effectively inhibiting the progression from precancerous lesions to invasive cancer in mouse models [8]. - The treatment not only reduced the proportion of pro-tumor M2 macrophages but also improved the immune surveillance of the precancerous microenvironment [8]. Group 6: Conclusion - The findings provide a crucial mechanistic basis for targeting immune suppression in precancerous stages and lay a solid foundation for early intervention strategies [11].

Core Viewpoint - The study identifies PILRα as a potential immune checkpoint in cancer immunotherapy, which interacts with T cell surface protein CD99 to suppress anti-tumor immunity, indicating its clinical significance in various human cancers with poor prognosis [2][4][5]. Group 1 - The research published in Nature Cancer reveals that PILRα expressed on tumor cells inhibits T cell activation, proliferation, and effector functions by targeting CD99, affecting the ZAP70/NFAT/IL-2/JAK/STAT signaling pathway [3]. - Blocking the interaction between PILRα and CD99 using specific antibodies significantly enhances T cell anti-tumor immune responses and suppresses tumor growth, showing synergistic effects when combined with anti-PD-1 antibodies [3][5]. - High expression of PILRα in various human cancers is associated with unfavorable prognosis, highlighting its potential as a therapeutic target in cancer treatment [4].