撰文丨王聪 编辑丨王多鱼 排版丨水成文 结直肠癌 （CRC） 是全球第三大常见癌症，在癌症相关死亡中排名第二，约 50% 的结直肠癌患者最终会 出现肝转移。在可行的情况下，对肝转移瘤进行手术切除可使 15% 至 20% 的患者获得总体生存率和无病 生存率提高的机会。然而，并非所有患者都能从根治性手术中获益，因为 50% 至 60% 的 结直肠癌肝转 移 （CRLM） 患者在切除术后会在肝脏内复发。这种复发通常是由未被发现的微小转移灶的生长或手术过 程中肿瘤细胞的扩散所引发的，这两者都受到围手术期变化的影响。 手术引起的免疫紊乱会改变宿主-肿瘤免疫环境，这可能会促进肿瘤复发。结直肠癌患者术后全身及局部炎 症均与较差的癌症预后直接相关。尽管已知存在这些关联，但我们对于手术引发的炎症如何促进肿瘤复发 的理解仍然有限。 2026 年 2 月 9 日，弗吉尼亚大学 Zhang Hongji 团队等在 Cell 子刊 Cell Reports Medicine 上发表了题 为： Preoperative exercise induces anti-tumor Kupffer cells to prevent surgic ...

编辑丨王多鱼 排版丨水成文 癌症相关成纤维细胞 （CAF） 是肿瘤微环境中的主要基质成分，然而它们的代谢状态在治疗期间如何转变 以及如何影响抗肿瘤免疫力，目前仍不清楚。 2026 年 2 月 12 日，中山大学肿瘤防治中心 刘卓炜 / 马梓坤 / 梁晓雨 团队联合暨南大学 何蓉蓉 团队， 在 Cancer Cell 期刊发表题为： Lipid Oxidation Reprogramming in Cancer-Associated Fibroblasts Enhances CD8 ⁺ T-Cell Cytotoxicity and Therapeutic Response 的研究论文。 该研究通过整合临床癌症样本、单细胞 RNA 分析和功能研究，鉴定出了一个由化疗诱导的 PTGER3 + CAF 亚群，其特征是脂质氧化增强，即 lipo-CAF ，这种代谢重编程通过抑制 PTEN 相关信号传导，促进 CD8 ⁺ T 细 细胞的活化和细胞毒性，从而增强了抗肿瘤免疫。在临床上，治疗诱导的 PTGER3 + CAF 比 例较高与改善的治疗响应和更好的患者预后相关。 这项研究揭示了一种先前未被认识的基质代谢适应机制， ...

Core Viewpoint - Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults, with a median survival of only 12-18 months post-diagnosis, and current treatments have limited efficacy in extending life expectancy [3] Group 1: Research Findings - A recent study published in Nature Cell Biology indicates that inhibiting lactate transport derived from tumor-associated macrophages (TAM) can restore cGAS-STING signaling and enhance antitumor immunity in glioblastoma [4] - The research team discovered that lactate is transported from TAM to glioblastoma stem cells (GSC) via MCT4-MCT1, promoting GSC proliferation and inducing lactylation modification of the non-homologous end joining protein KU70 at lysine 317 (K317), which inhibits cGAS-STING signaling and remodels the immunosuppressive tumor microenvironment [7] - Overall, the study reveals that lactate and lactylation modifications produced by TAM are key regulatory factors in maintaining the immunosuppressive tumor microenvironment in GSC, opening new avenues for combination therapies in glioblastoma [9]

Core Viewpoint - CAR-T cell therapy has shown remarkable clinical efficacy in hematological cancers, but approximately 30%-50% of patients experience disease relapse within one year post-treatment, highlighting the need for improved T cell persistence strategies [2][5]. Group 1: CAR-T Cell Therapy Challenges - Despite the success of CAR-T cell therapy, it is associated with severe toxicities, including cytokine release syndrome and neurotoxicity [2]. - The persistence of T cells is crucial for the efficacy and long-term remission of CAR-T cell therapy, influenced by factors such as the percentage of stem cell-like memory T cells and T cell proliferation capacity [2][5]. Group 2: New Research Developments - A study published by a team from the University of Southern California introduced a novel CAR structure driven by the ZAP327 signaling domain, which significantly reduces cytokine release and T cell exhaustion while generating robust and long-lasting antitumor immunity in mouse models [3][5]. - The ZAP327-driven CAR-T cells demonstrated superior therapeutic antitumor activity compared to traditional CAR-T cells, particularly in low antigen-expressing tumor models, leading to extended survival in mouse experiments [5][8]. Group 3: Mechanisms of Action - The ZAP327 domain modulates TCR signaling, increases the pool of stem cell-like memory T cells, and exhibits metabolic characteristics associated with memory T cells through oxidative phosphorylation pathways [6][8]. - The study emphasizes the potential of ZAP327-driven CAR-T cells to overcome the limitations of current CAR-T therapies and enhance T cell responses against solid tumors [8].

Core Viewpoint - Dietary restriction (DR) can extend the lifespan of mammals and delay age-related diseases, including cancer, through mechanisms that are not yet fully understood [1]. Group 1: Research Findings - A study published in Nature Metabolism indicates that dietary restriction leads to metabolic changes in ketone bodies, specifically increasing β-hydroxybutyrate (βOHB), which reprograms the fate and function of CD8+ T cells in the tumor microenvironment, enhancing anti-tumor immunity and responses to immunotherapy [1]. - In experiments, mice subjected to a 50% dietary restriction showed a significant slowdown in tumor growth and a survival extension of 30%-80% compared to those with free access to food [4]. - The anti-cancer effects of dietary restriction were found to be dependent on the immune system, particularly CD8+ T cells, as the effects disappeared in T cell-deficient mice [4]. Group 2: Mechanism of Action - CD8+ T cells, known as "killer cells," are responsible for identifying and destroying cancer cells, but often become "exhausted" in the tumor microenvironment [6]. - Dietary restriction promotes the expansion of effector T cell subsets with stronger anti-cancer capabilities while limiting the accumulation of terminally exhausted T cells [7]. - The mechanism behind this transformation is linked to ketone metabolism, where increased βOHB enhances mitochondrial function and energy metabolism in CD8+ T cells, thereby boosting their anti-cancer capabilities [8]. Group 3: Implications for Cancer Therapy - The study found that dietary restriction can synergize with existing cancer immunotherapies, such as PD-1 monoclonal antibodies, significantly improving treatment outcomes and even leading to complete tumor regression in some melanoma mouse models [9]. - The research suggests that dietary interventions could be a simple and effective strategy to enhance the efficacy of cancer immunotherapy [11]. - Given the challenges of implementing strict dietary restrictions in clinical settings, alternative approaches such as GLP-1 receptor agonists (e.g., semaglutide, tirzepatide) may simulate the metabolic effects of dietary restriction [11].

Core Viewpoint - The research highlights the potential of Vitamin B6, specifically its active form pyridoxal phosphate (PLP), in enhancing the stem-like characteristics and antitumor abilities of CD8+ T cells, suggesting its clinical application in cancer immunotherapy [2][10]. Group 1: Mechanism and Findings - Tumor-infiltrating lymphocytes (TILs) often exhibit dysfunction but can display stem-like behavior through unclear mechanisms [6]. - The study found that Vitamin B6 or PLP treatment enhances the persistence and stem-like phenotype of CD8+ T cells, improving their ability to eliminate tumors [6][8]. - PLP maintains T cell functionality by directly binding to and inhibiting p70S6 kinase (p70S6K), which in turn affects the phosphorylation of BACH2, promoting stem cell gene expression while suppressing exhaustion gene expression [6][11]. Group 2: Clinical Implications - In preclinical tumor models, PLP treatment improved the efficacy of anti-PD-1 monoclonal antibody therapy [7]. - The research underscores the clinical potential of strategies that enhance T cell functionality through Vitamin B6/PLP in cancer immunotherapy [10].

Core Insights - The study published by the team led by Academician Dong Chen from Westlake University in the journal Science highlights the role of Ms4a7 expression in cDC1 cells in promoting cross-activation of CD8+ T cells against tumors [2] - The absence of Ms4a7 in cDC1 cells impairs the specific CD8+ T cell response targeting tumors and weakens T cell immunity during bacterial and viral infections [2][4] - Human data analysis indicates that infiltration of MS4A7-expressing cDC1 cells is associated with enhanced CD8+ T cell tumor immunity and improved patient survival rates [2][4] Group 1 - cDC1 cells capture antigens in peripheral tissues and migrate to draining lymph nodes (dLN) to initiate antigen-specific CD8+ T cell immune responses [3] - The study found that Ms4a7 expression is upregulated in cDC1 cells upon tumor antigen uptake or exposure to external stimuli, which is essential for their cross-presentation capability [4] - Ms4a7 is located in antigen-processing vesicles, facilitating steps in the antigen presentation process without altering upstream uptake or degradation [6] Group 2 - The research reveals how tumor microenvironment signals regulate Ms4a7 expression in cDC1, enhancing their cross-presentation ability and CD8+ T cell activation [6] - In human cancers, the expression of MS4A7 correlates with robust interactions between cDC1 and T cells, leading to favorable clinical outcomes [6]

Core Insights - The study published in Nature Immunology reveals that chemotherapy-induced CA-repeat DNA fragments in breast cancer can trigger antitumor immune responses [3][4]. - The research highlights the relationship between genomic instability and immune regulation, emphasizing the therapeutic potential of CA-rich DNA in enhancing antitumor immunity [7]. Group 1 - The research team demonstrated that in tumors with low expression of MSH2, DNA fragments rich in CA, generated by DNA-damaging chemotherapy, preferentially bind with cGAS, leading to the formation of biomolecular condensates in the cytoplasm and triggering antitumor immune responses [7]. - In contrast, DNA fragments lacking CA released from tumors with high MSH2 expression activate AIM2, resulting in immune suppression through the upregulation of PD-L1 and IDO [7]. - The study found that the increase in CA-rich DNA fragments post-chemotherapy correlates with a rise in tumor antigen-responsive T cells and better chemotherapy responses [7]. Group 2 - The injection of CA-rich DNA fragments into tumors enhances antitumor immunity in PyMT allograft tumors [7]. - Different tumor DNA fragments can elicit opposing immune responses based on their preference for different sensors [7].

Core Viewpoint - The research highlights the immune-regulating properties of Zeaxanthin, a nutrient found in leafy vegetables and corn, which enhances CD8+ T cell function and improves anti-tumor immunity, indicating its potential as a dietary supplement in cancer therapy [3][10]. Group 1: Research Findings - Zeaxanthin is identified as an immune modulator that enhances the function of CD8+ effector T cells, thereby increasing anti-tumor immunity [3][10]. - Oral supplementation of Zeaxanthin improves the efficacy of anti-PD-1 immune checkpoint inhibitors and enhances the cytotoxicity of TCR-engineered CD8+ T cells against tumor cells [9][10]. - The study utilized a "blood nutrient" library to identify dietary nutrients that influence CD8+ T cell function, revealing that trans-18:1 fatty acid (TVA) also promotes CD8+ T cell activity and response to immunotherapy [6][8]. Group 2: Mechanisms of Action - Zeaxanthin enhances T cell receptor (TCR) signaling on CD8+ T cells, improving their functional response [9][10]. - The research indicates that the structural isomer Lutein does not exhibit the same immune-enhancing effects as Zeaxanthin, underscoring the unique properties of Zeaxanthin [8][10]. - The findings suggest that dietary components can play a significant role in modulating immune responses, particularly in the context of cancer treatment [5][12].

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].