Core Viewpoint - The source of dietary fat significantly influences anti-tumor immunity in obese individuals, with animal fats impairing immune response and promoting tumor growth, while plant fats do not have this negative effect [5][7][9]. Group 1: Research Findings - A study published in Nature Metabolism indicates that high-fat diets based on animal fats (lard, beef tallow, or butter) weaken anti-tumor immunity in obese mice and accelerate tumor growth [5][7]. - In contrast, high-fat diets based on plant oils (coconut oil, palm oil, or olive oil) do not exhibit this detrimental effect, with palm oil even enhancing anti-tumor immunity and slowing tumor growth in obese mice [5][7][9]. - The research highlights that the metabolic byproducts of animal fats, particularly long-chain acylcarnitines, strongly inhibit NK and CTL cells, leading to impaired immune function [9]. Group 2: Implications for Cancer Treatment - The findings suggest that dietary modifications, such as replacing animal fats with plant oils, could be beneficial for obese cancer patients undergoing treatment, potentially lowering their cancer risk [5][6][9]. - The study emphasizes the importance of dietary fat composition in maintaining a healthy immune system and improving treatment outcomes for obese individuals with cancer [9].

Core Viewpoint - The research indicates that social interaction in mice can suppress breast cancer progression through a specific neural circuit, providing a potential theoretical basis for clinical applications of social support in tumor treatment [4][10]. Summary by Sections Research Findings - Social interaction activates neural circuits that inhibit breast cancer progression [8] - ACC Glu neurons are crucial for the anti-tumor effects of social interaction [8] - The ACC Glu → BLA Glu circuit mediates the anti-tumor benefits of social interaction [8] - Artificial activation of the social interaction circuit can enhance anti-tumor immune responses [8] Implications - The study suggests that social interaction may influence tumor progression by modulating sympathetic nerve activity and norepinephrine release, potentially reshaping anti-tumor immunity [6][10].

Core Viewpoint - Exercise is recognized as a significant factor in reducing cancer risk, enhancing the survival of cancer patients, and improving treatment outcomes, particularly through its effects on the gut microbiome and immune response [2][4][6]. Group 1: Research Findings - A study published in the journal Cell indicates that exercise induces the production of the gut microbiota metabolite formate, which enhances CD8 T cell antitumor immunity and improves the efficacy of cancer immunotherapy [3][4]. - The research highlights that the gut microbiome's metabolic products, rather than the microbiome itself, are crucial for the antitumor effects of exercise [9][10]. - The study identifies Nrf2 as a key mediator in the enhancement of Tc1 cell function driven by formate, both in vitro and in vivo [11]. Group 2: Implications for Cancer Treatment - The findings suggest that high-producing formate gut microbiota in humans can enhance tumor suppression and promote robust antitumor Tc1 immune responses, indicating formate as a potential biomarker for enhancing Tc1-mediated antitumor immunity [12][15]. - The research opens avenues for developing treatment strategies that combine exercise with microbiota-derived metabolites, particularly focusing on Nrf2 agonists like formate for patients resistant to immune checkpoint inhibitors [16][17].

Core Viewpoint - The study highlights the critical role of dendritic cell (DC) interstitial motility in sustaining anti-tumor immunity, revealing that impaired migration in a disordered tumor microenvironment (TME) promotes tumor immune evasion, while enhancing this motility offers promising directions for dendritic cell-centered immunotherapy [5][15]. Group 1: Research Findings - The research published by the team from Westlake University indicates a gradual decline in migratory conventional dendritic cells (mig-cDC) in tumor-draining lymph nodes (tdLN) during tumor progression, which hampers the initial activation of tumor-specific T cells and their subsequent delivery to the TME, leading to immune evasion [4][11]. - A genome-wide CRISPR screening identified phosphodiesterase 5 (PDE5) and its substrate cGMP as key regulators of dendritic cell migration, with late-stage tumors disrupting cGMP synthesis in dendritic cells, thereby reducing their migratory capacity [4][12]. - The use of the PDE5 inhibitor sildenafil was shown to restore cGMP levels and enhance the migration of mig-cDC to tdLN, thereby maintaining anti-tumor immunity [12][14]. Group 2: Mechanisms and Implications - The study elucidates the NOS2-NO-sGC-PDE5 signaling axis, which maintains cGMP levels and determines dendritic cell migration ability, emphasizing the importance of this pathway in anti-tumor immunity [13]. - Sildenafil, commonly known for treating erectile dysfunction, has been observed to have anti-tumor effects, which this research provides an immunological mechanism for, suggesting its potential in enhancing dendritic cell function in cancer therapy [14][15]. - The findings suggest that enhancing the interstitial motility of dendritic cells could be a promising strategy for developing dendritic cell-based immunotherapies, addressing the challenges posed by the TME [5][15].

Core Viewpoint - The article discusses the role of Interleukin-15 (IL-15) in enhancing anti-tumor immunity, particularly through the activation of Natural Killer (NK) cells, and highlights recent research that identifies UBE2F as a key target for improving NK cell response to IL-15 [2][6][7]. Group 1 - IL-15 is a cytokine that promotes the generation of immune cells capable of detecting and killing cancer cells, such as NK cells [1]. - Cancer cells have evolved mechanisms to evade immune detection, prompting researchers to explore IL-15 receptor agonists to induce anti-tumor immune responses, although toxicity has limited clinical development [2][6]. - A study published by oNKo-innate and Monash University reveals that knocking out the UBE2F gene in NK cells significantly enhances their sensitivity to low doses of IL-15, improving their anti-cancer capabilities and slowing colorectal cancer growth in preclinical models [2][4]. Group 2 - The research team conducted a whole-genome CRISPR screening to uncover the complete IL-15R signaling mechanism in NK cells, identifying ubiquitin-dependent IL-15R degradation as a major inhibitory mechanism [4][5]. - Key targets discovered include UBE2F, ARIH2, and members of the Cullin-5 RING E3 ligase complex, with UBE2F being essential for the ubiquitination and activation of CUL5, while ARIH2 aids in the degradation of IL-15RB mediated by CRL5 [5][6]. - The absence of UBE2F was shown to inhibit CRL5 activity, thereby enhancing NK cell responsiveness to IL-15, with mouse model studies indicating improved anti-tumor immunity against both primary and metastatic tumors [6]. Group 3 - UBE2F, as an enzyme, presents a potential target for small molecule inhibitors, with existing drugs that block UBE2F already tested in patients with myelodysplastic syndromes to induce cancer cell death [7]. - The research team expresses confidence in discovering more specific inhibitors with better safety profiles for testing in environments where immunotherapy is less effective and requires enhanced immune responses against cancer [7].

Core Viewpoint - The discovery of a new type of cell death called disulfidptosis opens new avenues for cancer treatment, particularly through targeting SLC7A11 protein and lactate dehydrogenase B (LDHB) in tumor-infiltrating CD8⁺ T cells [1][2][11]. Group 1: Disulfidptosis Discovery - In February 2023, a team from the University of Texas MD Anderson Cancer Center identified disulfidptosis, triggered by glucose deprivation in cells with high SLC7A11 expression, which effectively inhibits tumor growth without harming normal tissues [1]. - The research indicates that disulfidptosis is driven by the abnormal accumulation of disulfides, particularly in cancer cells under glucose starvation conditions [11]. Group 2: Role of LDHB in Immune Response - A study published in June 2025 revealed that LDHB promotes disulfidptosis and exhaustion of tumor-infiltrating CD8⁺ T cells, leading to impaired anti-tumor immunity, suggesting LDHB as a potential target in cancer immunotherapy [2][6]. - The mechanism involves LDHB limiting the activity of glucose-6-phosphate dehydrogenase (G6PD) in exhausted CD8⁺ T cells, resulting in NADPH depletion and subsequent disulfidptosis-mediated cell death [6][7]. Group 3: Implications for Cancer Immunotherapy - The findings highlight the distinct roles of disulfidptosis and ferroptosis in driving CD8⁺ T cell exhaustion, indicating that targeting LDHB could be a promising therapeutic strategy in cancer immunotherapy [9]. - The research expands the understanding of disulfidptosis, showing its impact on the functionality of CD8⁺ T cells and its potential implications for enhancing anti-tumor immune responses [11].

Core Viewpoint - The study highlights that intravesical administration of Bacillus Calmette-Guérin (BCG) vaccine can reprogram hematopoietic stem/progenitor cells (HSPC) to enhance anti-tumor immunity, indicating its potential in cancer immunotherapy [1][2][4][6]. Group 1: Mechanism of Action - BCG vaccine can colonize the bone marrow and reprogram HSPC, enhancing myeloid hematopoiesis in both mice and humans [3][4]. - The reprogrammed HSPC can generate neutrophils, monocytes, and dendritic cells, which reshape the tumor microenvironment and drive T cell-dependent anti-tumor responses [3][4]. Group 2: Key Findings - The study confirms that intravesical BCG administration leads to systemic reprogramming of HSPC [4]. - The reprogramming of HSPC is dependent on INFγ and enhances the antigen-presenting function of myeloid cells [4]. - Reprogrammed myeloid cells increase T cell infiltration and work synergistically with PD-1 blockade for anti-cancer effects [4][6]. Group 3: Implications - The findings underscore the broad potential of HSPC reprogramming in enhancing T cell-dependent tumor immunity, suggesting a novel approach in cancer treatment [6].

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].