Cancer letters最新文献

{"title":"Mechanisms of Low MHC I Expression and Strategies for Targeting MHC I with Small Molecules in Cancer Immunotherapy.","authors":"Shijia Kong, Jie Zhang, Longsheng Wang, Wen Li, Hongjie Guo, Qiaojun He, Honggang Lou, Ling Ding, Bo Yang","doi":"10.1016/j.canlet.2024.217432","DOIUrl":"https://doi.org/10.1016/j.canlet.2024.217432","url":null,"abstract":"<p><p>Major histocompatibility complex (MHC) class I load antigens and present them on the cell surface, which transduces the tumor-associated antigens to CD8⁺ T cells, activating the acquired immune system. However, many tumors downregulate MHC I expression to evade immune surveillance. The low expression of MHC I not only reduce recognition by- and cytotoxicity of CD8⁺ T cells, but also seriously weakens the anti-tumor effect of immunotherapy by restoring CD8⁺ T cells, such as immune checkpoint inhibitors (ICIs). Accumulated evidence suggested that restoring MHC I expression is an effective strategy for enhancing tumor immunotherapy. This review focuses on mechanisms underlying MHC I downregulation include gene deletion and mutation, transcriptional inhibition, reduced mRNA stability, increased protein degradation, and disruption of endocytic trafficking. We also provide a comprehensive review of small molecules that restore or upregulate MHC I expression, as well as clinical trials involving the combination of ICIs and these small molecule drugs.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217432"},"PeriodicalIF":9.1,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prostate Luminal Cell Plasticity and Cancer.","authors":"Emily C Williams, Maho Shibata","doi":"10.1016/j.canlet.2024.217430","DOIUrl":"https://doi.org/10.1016/j.canlet.2024.217430","url":null,"abstract":"<p><p>Cellular plasticity in prostate cancer promotes treatment resistance. Several independent studies have used mouse models, single-cell RNA sequencing, and genetic lineage tracing approaches to characterize cellular differentiation and plasticity during prostate organogenesis, homeostasis and androgen-mediated tissue regeneration. We review these findings and recent work using immune-competent genetically-engineered mouse models to characterize cellular plasticity and clonal dynamic changes during prostate cancer progression. Collectively these studies highlight the influence of the tumor microenvironment and the function of epigenetic regulators in promoting cellular plasticity. How the epigenetic alternations that promote cell plasticity affect tumor immunogenicity remains an active area of research with implications for disease treatment.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217430"},"PeriodicalIF":9.1,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Histone lactylation-driven YTHDC1 promotes hepatocellular carcinoma progression via lipid metabolism remodeling.","authors":"Wenfei Du, Sheng Tan, Yonglin Peng, Sang Lin, Yunqiang Wu, Keshuo Ding, Changyu Chen, Ruiqi Liu, Yu Cao, Zheyi Li, Sijie Gu, Haoran Feng, Bingbing Wan, Sheng-Ce Tao, Niansong Wang, Ying Fan, Xiaodong Zhao","doi":"10.1016/j.canlet.2024.217426","DOIUrl":"10.1016/j.canlet.2024.217426","url":null,"abstract":"<p><p>Lipid metabolism reprogramming is critical for the initiation and progression of hepatocellular carcinoma (HCC). However, how the dysregulation of lipid metabolism contributes to HCC development remains largely unknown. Here, we report that the m⁶A reader YTHDC1-mediated epigenetic regulation of the long noncoding RNA NEAT1 activates stearoyl-CoA desaturase (SCD)-associated lipid metabolic processes during HCC progression. Mechanistically, histone lactylation in HCC induces increased expression of YTHDC1, increasing the stability of m⁶A-modified NEAT1. The histone acetyltransferase p300 is then recruited by NEAT1 and activates SCD by increasing the level of histone acetylation at the SCD promoter, thus facilitating HCC progression via hepatocellular lipid metabolism remodeling. Taken together, these discoveries suggest a close link between the epigenetic machinery and lipid metabolic abnormalities, which promotes cancer progression.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217426"},"PeriodicalIF":9.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nervous system in colorectal cancer.","authors":"Chunjie Xu, Chunhui Jiang, Yuan Tian, Ye Liu, Hao Zhang, Zeyu Xiang, Hanbing Xue, Lei Gu, Qing Xu","doi":"10.1016/j.canlet.2024.217431","DOIUrl":"https://doi.org/10.1016/j.canlet.2024.217431","url":null,"abstract":"<p><p>A malignant tumor is a complex systemic disease involving the nervous system, which regulates nerve signals. Cancer neuroscience is a field that explores the interactions between tumors and the nervous system. The gastrointestinal tract is a typical peripheral organ with abundant neuroregulation and is regulated by the peripheral, enteric, and central nervous systems (PNS, ENS, and CNS, respectively). The physiological functions of the gastrointestinal tract are maintained via complex neuromodulation. Neuroregulatory imbalance is the primary cause of gastrointestinal diseases, including colorectal cancer (CRC). In CRC, there is a direct interaction between the nervous system and tumor cells. Moreover, this tumor-nerve interaction can indirectly regulate the tumor microenvironment, including the microbiota, immunity, and metabolism. In addition to the lower nerve centers, the stress response, emotion, and cognition represented by the higher nerve centers also participate in the occurrence and progression of CRC. Herein, we review some basic knowledge regarding cancer neuroscience and elucidate the mechanism underlying tumor-nerve interactions in CRC.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217431"},"PeriodicalIF":9.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increased phosphorylation of AMPKα1 S485 in colorectal cancer and identification of PKCα as a responsible kinase.","authors":"Yan Zhou, Tingting Lei, Zhimin Tang, Pei Guo, Deqiang Huang, Zhijun Luo, Linyu Luo","doi":"10.1016/j.canlet.2024.217418","DOIUrl":"10.1016/j.canlet.2024.217418","url":null,"abstract":"<p><p>The present study attempts to examine the biological effect of phosphorylation of AMPKα1 S485 and identify the responsible kinase in colon cancer cells. Thus, our results showed that S485 phosphorylation was increased in colorectal cancer specimens as compared with adjacent normal tissues, which was inversely correlated to phosphorylation of T172. Our study further revealed that phosphorylation of S485 on AMPKα1 plays a promoting role in cell proliferation, colony formation, migration and growth of Xenograft tumor. Furthermore, we identified PKCα as a kinase specific for phosphorylation of S485. First, under the basal condition, S485 phosphorylation was blunted by Gö6983, a pan PKC inhibitor, but not by Akt inhibitor, MK2206, although the latter countered off the insulin-stimulated phosphorylation. Second, the phosphorylation was enhanced by PMA and attenuated by sgRNA for PKCα, but not by PKCγ and PKCδ, neither by siRNA for Akt1. Third, the phosphorylation was suppressed by shRNA for PLCγ1. Fourth, the phosphorylation was enhanced by ectopically expressing a constitutively active mutant of PKCα, but not PKCγ. Finally, the increase of S485 phosphorylation by high glucose or palmitic acid was almost completely abolished by Gö6983. Altogether, our data reinforced the tumor suppressive function of AMPK and demonstrated that PKCα is a major kinase responsible for phosphorylation of S485, which contributes to one of the mechanisms underlying the regulation of AMPK in cancer cells in response to nutritional conditions.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217418"},"PeriodicalIF":9.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sulforaphane potentiates the efficacy of chemoradiotherapy in glioblastoma by selectively targeting thioredoxin reductase 1.","authors":"Yuqian Ge, Zehe Ge, Fuwei Tian, Xiaoyu Tai, Dongyin Chen, Shuhong Sun, Zhumei Shi, Jianxing Yin, Guining Wei, Dongmei Li, Lude Wang, Wenxia Xu, Minfeng Tong, Fang Liu, Lin Zhao, Xu Qian, Xin Ge","doi":"10.1016/j.canlet.2024.217429","DOIUrl":"https://doi.org/10.1016/j.canlet.2024.217429","url":null,"abstract":"<p><p>Chemoradiotherapy is a conventional treatment modality for patients with glioblastoma (GBM). However, the efficacy of this approach is significantly hindered by the development of therapeutic resistance. The thioredoxin system, which plays a crucial role in maintaining redox homeostasis, confers protection to cancer cells against apoptosis induced by chemoradiotherapy. Herein, we demonstrate that sulforaphane (SFN), an isothiocyanate phytochemical with anti-cancer effects, inhibits the activity of thioredoxin reductase 1 (TrxR1) through covalent conjugation with residues C59/64/497&U498. This inhibition of TrxR1 leads to the accumulation of reactive oxygen species (ROS), thereby enhancing chemoradiotherapy-induced apoptosis in GBM cells. Furthermore, SFN-induced ROS accumulation facilitates the polarization of M1-like macrophages, which synergistically sensitize GBM tumors to chemoradiotherapy. In conclusion, our study unveils that SFN has potential benefits in improving the effect of chemoradiotherapy and prognosis for GBM patients by targeting TrxR1.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217429"},"PeriodicalIF":9.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Driver mutation landscape of acute myeloid leukemia provides insights for neoantigen-based immunotherapy.","authors":"Peng Jin, Jie Shen, Ming Zhao, Jinyi Yu, Wen Jin, Ge Jiang, Zeyi Li, Mengke He, Xiaxin Liu, Shishuang Wu, Fangyi Dong, Yuncan Cao, Hongming Zhu, Xiaoyang Li, Xiaoling Wang, Yunxiang Zhang, Zhen Jin, Kankan Wang, Junmin Li","doi":"10.1016/j.canlet.2024.217427","DOIUrl":"https://doi.org/10.1016/j.canlet.2024.217427","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) has lagged in benefiting from immunotherapies, primarily due to the scarcity of actionable AML-specific antigens. Driver mutations represent promising immunogenic targets, but a comprehensive characterization of the AML neoantigen landscape and their impact on patient outcomes and the AML immune microenvironment remain unclear. Herein, we conducted matched DNA and RNA sequencing on 304 AML patients and extensively integrated data from additional ∼2,500 AML cases, identifying 49 driver genes, notably characterized by a significant proportion of insertions and deletions (indels). Neoantigen analysis showed that indels triggered a higher abundance of neoantigens both in quantity and quality compared to single nucleotide variants (SNVs) and gene fusions. By integrating peptide features pertinent to neoantigen presentation and T cell recognition, we developed two robust models of epitope immunogenicity that significantly enriched immunogenic neoepitopes. We validated 30 neoantigens through in vitro direct binding assays of predicted peptides to MHC proteins and confirmed the immunogenicity of 20 neoantigens using interferon-γ ELISpot and tetramer assays. Moreover, we demonstrated that patients with higher neoantigen loads, derived from driver mutations, exhibited poor clinical outcomes and an IFN-driven adaptive immune response, which was associated with immune suppression and tumor evasion. Through deconvolution of large-scale bulk transcriptomes, integration of single-cell RNA sequencing and multiparametric flow cytometry, we confirmed a strong association between neoantigen load and CD8⁺ T cell exhaustion. This study provides a comprehensive landscape of AML neoantigens derived from driver mutations, offering putative immunogenic targets and emphasizing the need for strategies to revitalize the immunosuppressive milieu.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217427"},"PeriodicalIF":9.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor metastasis and recurrence: The role of perioperative NETosis.","authors":"Fu Zeng, Yuwen Shao, Jingyi Wu, Jingwen Luo, Ying Yue, Yang Shen, Yanghanzhao Wang, Yuxin Shi, Dan Wu, Juan P Cata, Shuofei Yang, Hao Zhang, Changhong Miao","doi":"10.1016/j.canlet.2024.217413","DOIUrl":"https://doi.org/10.1016/j.canlet.2024.217413","url":null,"abstract":"<p><p>Although surgical resection of tumor mass remains the mainstay of curative therapeutic management for solid tumors, accumulating studies suggest that these procedures promote tumor recurrence and metastasis. Regarded as the first immune cells to fight against infectious or inflammatory insults from surgery, neutrophils along with their ability of neutrophil extracellular traps (NETs) production has attracted much attention. A growing body of evidence suggests that NETs promote cancer metastasis by stimulating various stages, including local invasion, colonization, and growth. Therefore, we discussed the mechanism of NETosis induced by surgical stress and tumor cells, and the contribution of NETs on tumor metastasis: aid in the tumor cell migration and proliferation, evasion of immune surveillance, circulating tumor cell adhesion and establishment of a metastatic niche. Lastly, we summarized existing NET-targeting interventions, offering recent insights into potential targets for clinical intervention.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"611 ","pages":"217413"},"PeriodicalIF":9.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892282","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TIM3 on natural killer cells regulates antibody-dependent cellular cytotoxicity in HER2-positive gastric cancer.","authors":"Chikanori Tsutsumi, Kenoki Ohuchida, Hirono Tsutsumi, Yuki Shimada, Yutaka Yamada, Kiwa Son, Sayuri Hayashida, Naoki Katayama, Yuki Mochida, Chika Iwamoto, Nobuhiro Torata, Kohei Horioka, Koji Shindo, Yusuke Mizuuchi, Naoki Ikenaga, Kohei Nakata, Keiichi Ota, Eiji Iwama, Masami Yamamoto, Tetsuya Tsukamoto, Sachiyo Nomura, Takashi Morisaki, Yoshinao Oda, Isamu Okamoto, Masafumi Nakamura","doi":"10.1016/j.canlet.2024.217412","DOIUrl":"https://doi.org/10.1016/j.canlet.2024.217412","url":null,"abstract":"<p><p>Therapies targeting HER2 are the standard treatment for HER2-positive gastric cancer (GC). Trastuzumab, a monoclonal antibody against HER2, exerts anti-tumor activity through cell growth regulation and antibody-dependent cellular cytotoxicity (ADCC). ADCC is induced by the binding of trastuzumab to Fcγ receptor III (CD16) in natural killer (NK) cells. However, the relationship between immune checkpoint (IC) molecules of NK cells and trastuzumab-induced ADCC is poorly understood. We performed single-cell RNA sequencing (scRNA-seq) and immunohistochemistry to identify IC molecules associated with CD16 expression in NK cells of GC patients. Additionally, we conducted in vitro assays with HER2-transfected GC cells and in vivo experiments using a mouse HER2-positive GC model to assess expression changes in IC molecules in NK cells and their ligands during trastuzumab treatment. In GC patients, the expression of TIM3, an IC molecule, was strongly correlated with that of CD16 in NK cells. In vitro assays showed that ADCC with trastuzumab increased TIM3 expression in NK cells. scRNA-seq analysis revealed that TIM3 expression of cytotoxic NK cells was elevated in HER2-positive GC patients treated with trastuzumab. HMGB1, a TIM3 ligand, was expressed at higher levels in HER2-transfected GC cells than in controls. Furthermore, HMGB1 expression was higher in HER2-positive GC patients treated with trastuzumab compared to untreated HER2-positive GC patients. In the mouse HER2-positive GC model, anti-TIM3 antibodies and trastuzumab demonstrated synergistic anti-tumor effects without toxicity. This study suggests the combined anti-TIM3 antibody and trastuzumab therapy may have potential as a new treatment strategy for HER2-positive GC.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"611 ","pages":"217412"},"PeriodicalIF":9.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A mechanistic, functional, and clinical perspective on targeting CD70 in cancer.","authors":"Sandeep Kumar, Sowdhamini Mahendiran, Rakesh Sathish Nair, Harsh Vyas, Sunil Kumar Singh, Piush Srivastava, Saket Jha, Basabi Rana, Ajay Rana","doi":"10.1016/j.canlet.2024.217428","DOIUrl":"10.1016/j.canlet.2024.217428","url":null,"abstract":"<p><p>The oncoimmunology research has witnessed notable advancements in recent years. Reshaping the tumor microenvironment (TME) approach is an effective method to improve antitumor immune response. The T cell-mediated antitumor response is crucial for favorable therapeutic outcomes in several cancers. The United States Food and Drug Administration (FDA) has approved immune checkpoint inhibitors (ICIs) for targeting the immune checkpoint proteins (ICPs) expressed in various hematological and solid malignancies. The ICPs are T cell co-inhibitory molecules that block T cell activation and, thus, antitumor response. Currently, most of the FDA-approved ICIs are antagonistic antibodies of programmed death-ligand 1 (PD-L1), programmed cell death protein 1 (PD-1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). In contrast to ICPs, the T cell costimulatory molecules are required for T cell activation, expansion, and effector function. However, the abrupt expression of these costimulatory molecules in tumors presents a concern for T cell-mediated antitumor response. One of the T cell costimulatory molecules, the cluster of differentiation 70 (CD70), has emerged as a druggable target in various hematological and solid malignancies due to its role in T cell effector function and immune evasion. The present review describes the expression of CD70, factors affecting the CD70 expression, the physiological and clinical relevance of CD70, and the current approaches to target CD70 in hematological and solid malignancies.</p>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217428"},"PeriodicalIF":9.1,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}