{"title":"Elucidating the synergistic roles of CD4+ T and dendritic cells in antitumor immunity.","authors":"Xiubao Ren","doi":"10.20892/j.issn.2095-3941.2024.0453","DOIUrl":"https://doi.org/10.20892/j.issn.2095-3941.2024.0453","url":null,"abstract":"","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Osimertinib exacerbates immune checkpoint inhibitor-related severe adverse events by activating the IL-6/JAK/STAT3 pathway in macrophages.","authors":"Yuan Li, Yanping Chen, Yuan Meng, Meng Shen, Fan Yang, Xiubao Ren","doi":"10.20892/j.issn.2095-3941.2024.0269","DOIUrl":"https://doi.org/10.20892/j.issn.2095-3941.2024.0269","url":null,"abstract":"<p><strong>Objective: </strong>The combination of epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) and immune checkpoint inhibitors (ICIs) leads to an increased incidence of severe immune-related adverse events (irAEs). However, the mechanisms underlying macrophages in irAEs have not been elucidated.</p><p><strong>Methods: </strong>An osimertinib and ICI-induced irAE mouse model was constructed. Lung micro-CT scans were used to assess the degree of inflammatory infiltration. Hematoxylin-eosin staining was used to analyze the histopathologic inflammatory infiltration in mouse liver and lung tissues. Flow cytometry was used to detect the percentages of T cells, NK cells, and macrophages and the expression of EGFR. Enzyme-linked immunosorbent assay (ELISA) was used to detect the serum interleukin (IL)-6, alanine transaminase (ALT), ferritin, and tumor necrosis factor (TNF)-α levels. Total RNA extracted from mouse liver macrophages was analyzed by RNA-seq. Simple Western blot analysis was used to detect the IL-6/JAK/STAT3 pathway activation state.</p><p><strong>Results: </strong>Osimertinib combined with ICIs upregulated EGFR expression on macrophages with increased serum IL-6, ALT, and ferritin levels. RNA-seq and simple Western blot analysis of mouse liver macrophages confirmed that that the IL-6/JAK/STAT3 pathway was activated in the combination treatment group. Ruxolitinib blocked the IL-6/JAK/STAT3 pathway and significantly decreased the serum IL-6, ALT, and ferritin levels in the combination treatment group.</p><p><strong>Conclusions: </strong>An osimertinib and ICI-induced irAE mouse model was constructed that showed osimertinib combined with ICIs inhibited EGFR phosphorylation and activated the IL-6/JAK/STAT3 signaling pathway in mouse liver macrophages, which led to the release of relevant cytokines.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Adenosine signaling in tumor-associated macrophages and targeting adenosine signaling for cancer therapy.","authors":"Lei Yang, Yi Zhang, Li Yang","doi":"10.20892/j.issn.2095-3941.2024.0228","DOIUrl":"https://doi.org/10.20892/j.issn.2095-3941.2024.0228","url":null,"abstract":"<p><p>This review examined the critical role of adenosine signaling in modulating the behavior of tumor-associated macrophages (TAMs), a key determinant of the tumor microenvironment (TME). Adenosine is an immunosuppressive metabolite that is highly enriched in the TME due to elevated expression of adenosine triphosphatase (ATPase). Adenosine influences polarization of TAMs through A2A and A2B receptors, which drives a phenotype that supports tumor progression and immune evasion. The adenosine-mediated regulation of TAMs significantly suppresses the TME, dampening the efficacy of current immunotherapies. Targeting the adenosine pathway has shown potential in preclinical studies through reversal of the immunosuppressive microenvironment and antitumor immune response enhancement. Clinical trials are currently underway to determine the impact of A2A receptor antagonists, and CD39 and CD73 inhibition, enzymes that are pivotal in adenosine production, in various cancers. The current understanding of the CD39-CD73-adenosine axis in TAM regulation and the emerging strategies targeting adenosine signaling pathway for therapeutic intervention are the subjects of this review. The current clinical trials focusing on adenosine pathway inhibitors in combination with existing therapies to improve clinical outcomes are summarized and the need for continued research to refine these approaches for cancer treatment is emphasized.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Tumor-related fungi and crosstalk with gut fungi in the tumor microenvironment.","authors":"Yue Wang, Yiwen Wang, Yuhang Zhou, Yun Feng, Tao Sun, Junnan Xu","doi":"10.20892/j.issn.2095-3941.2024.0240","DOIUrl":"https://doi.org/10.20892/j.issn.2095-3941.2024.0240","url":null,"abstract":"<p><p>Most studies on the human gut microbiome have focused on the bacterial fraction rather than fungal biomics, which as resulted in an incomplete understanding of the fungal microbiome. Recent advances in microbiota detection and next-generation sequencing technology have boosted an increase in research on fungi. Symbiotic fungi have become increasingly influential in health and disease and modulate various physiologic functions within the host. Fungal infections can result in high morbidity and mortality rates and are life-threatening in some immunocompromised patients. In addition to bacterial dysbiosis, alterations in fungal communities are important and have been linked to many diseases, including asthma, mental illness, and various cancers. When investigating cancer it is imperative to consider the role of fungi alongside viruses and bacteria. This review examined the impact of intestinal fungi and peri-tumor fungi on tumorigenesis, cancer progression, and response to anticancer therapies. The review highlights the specific involvement of some fungal species in cancers include digestive tract tumors such as colorectal, pancreatic, liver, and gastric cancers, as well as non-digestive tract tumors such as lung, melanoma, breast, and ovarian cancers. Furthermore, fungal mechanisms of action, including fungus-host recognition and immune regulation, biofilm formation, toxin and metabolite production in the tumor microenvironment, and the complex effects of fungus-bacteria interactions on tumorigenesis and development, highlight the significance of potential biomarkers in cancer diagnosis and treatment.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142726122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Modulation of gut microbiota in targeted cancer therapy: insights on the EGFR/VEGF/KRAS pathways.","authors":"Li Gong, Shixue Yang, Junli Huang, Yongsheng Li","doi":"10.20892/j.issn.2095-3941.2024.0320","DOIUrl":"https://doi.org/10.20892/j.issn.2095-3941.2024.0320","url":null,"abstract":"<p><p>The rise in the incidence of cancer globally has led to a heightened interest in targeted therapies as a form of anticancer treatment. Key oncogenic targets, including epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), and kirsten rat sarcoma viral oncogene homologue (KRAS), have emerged as focal points in the development of targeted agents. Research has investigated the impact of gut microbiota on the efficacy of various anticancer therapies, such as immunotherapy, chemotherapy, and radiotherapy. However, a notable gap exists in the literature regarding the relationship between gut microbiota and targeted agents. This review emphasizes how specific gut microbiota and gut microbiota metabolites, including butyrate, propionate, and ursodeoxycholic acid, interact with oncogenic pathways to modulate anti-tumor effects. Conversely, deoxycholic acid, lipopolysaccharide, and trimethylamine n-oxide may exert pro-tumor effects. Furthermore, modulation of the gut microbiota influences glucose and lipid metabolism, thereby enhancing the response to anti-KRAS agents and addressing diarrhea induced by tyrosine kinase inhibitors. By elucidating the connection between gut microbiota and the EGFR/VEGF/KRAS pathways, this review provides valuable insights for advancing targeted cancer therapy and optimizing treatment outcomes in clinical settings.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142725844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Heliang Wu, Yi Wang, Yulin Lin, Ru Ma, Xuemei Du, Yandong Su, Rui Yang, Zhiran Yang, Xinli Liang, Yinguang Zhang, Xiaoqing Liang, Zhonghe Ji, Chunning Lai, Yajing Huang, Yan Li
{"title":"Potential treatment approaches for malignant peritoneal mesothelioma: in vivo and in vitro experimental study of natural killer cell immunotherapy.","authors":"Heliang Wu, Yi Wang, Yulin Lin, Ru Ma, Xuemei Du, Yandong Su, Rui Yang, Zhiran Yang, Xinli Liang, Yinguang Zhang, Xiaoqing Liang, Zhonghe Ji, Chunning Lai, Yajing Huang, Yan Li","doi":"10.20892/j.issn.2095-3941.2024.0218","DOIUrl":"https://doi.org/10.20892/j.issn.2095-3941.2024.0218","url":null,"abstract":"<p><strong>Objective: </strong>Malignant peritoneal mesothelioma (MPM) is a rare primary malignant tumor with an extremely poor prognosis that currently lacks effective treatment options. This study investigated the <i>in vitro</i> and <i>in vivo</i> efficacy of natural killer (NK) cells for treatment of MPM.</p><p><strong>Methods: </strong>An <i>in vitro</i> study was conducted to assess the cytotoxicity of NK cells from umbilical cord blood to MPM cells with the use of a high-content imaging analysis system, the Cell Counting Kit-8 assay, and Wright-Giemsa staining. The level of NK cell effector molecule expression was detected by flow cytometry and enzyme-linked immunosorbent assays. The ability of NK cells to kill MPM cells was determined based on live cell imaging, transmission electron microscopy, and scanning electron microscopy. An <i>in vivo</i> study was conducted to assess the efficacy and safety of NK cell therapy based on the experimental peritoneal cancer index, small animal magnetic resonance imaging, and conventional histopathologic, cytologic, and hematologic studies.</p><p><strong>Results: </strong>NK cells effectively killed MPM cells through the release of effector molecules (granzyme B, perforin, interferon-γ, and tumor necrosis factor-α) in a dose- and density-dependent manner. The NK cell killing process potentially involved four dynamic steps: chemotaxis; hitting; adhesion; and penetration. NK cells significantly reduced the tumor burden, diminished ascites production, and extended survival with no significant hematologic toxicity or organ damage in NOG mice.</p><p><strong>Conclusions: </strong>NK cell immunotherapy inhibited proliferation of MPM cells <i>in vitro</i> and <i>in vivo</i> with a good safety profile.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":" ","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557259","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jianlin Shen, Yue Lai, Yanjiao Wu, Xuan Lin, Cheng Zhang, Huan Liu
{"title":"Ubiquitination in osteosarcoma: unveiling the impact on cell biology and therapeutic strategies.","authors":"Jianlin Shen, Yue Lai, Yanjiao Wu, Xuan Lin, Cheng Zhang, Huan Liu","doi":"10.20892/j.issn.2095-3941.2024.0231","DOIUrl":"10.20892/j.issn.2095-3941.2024.0231","url":null,"abstract":"<p><p>Ubiquitination, a multifaceted post-translational modification, regulates protein function, degradation, and gene expression. The pivotal role of ubiquitination in the pathogenesis and progression of cancer, including colorectal, breast, and liver cancer, is well-established. Osteosarcoma, an aggressive bone tumor predominantly affecting adolescents, also exhibits dysregulation of the ubiquitination system, encompassing both ubiquitination and deubiquitination processes. This dysregulation is now recognized as a key driver of osteosarcoma development, progression, and chemoresistance. This review highlights recent progress in elucidating how ubiquitination modulates tumor behavior across signaling pathways. We then focus on the mechanisms by which ubiquitination influences osteosarcoma cell function. Finally, we discuss the potential for targeting the ubiquitin-proteasome system in osteosarcoma therapy. By unraveling the impact of ubiquitination on osteosarcoma cell physiology, we aim to facilitate the development of novel strategies for prognosis, staging, treatment, and overcoming chemoresistance.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":"21 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoning Gan, Guanqi Dai, Yonghao Li, Lin Xu, Guolong Liu
{"title":"Intricate roles of estrogen and estrogen receptors in digestive system cancers: a systematic review.","authors":"Xiaoning Gan, Guanqi Dai, Yonghao Li, Lin Xu, Guolong Liu","doi":"10.20892/j.issn.2095-3941.2024.0224","DOIUrl":"10.20892/j.issn.2095-3941.2024.0224","url":null,"abstract":"<p><p>Gender disparities are evident across different types of digestive system cancers, which are typically characterized by a lower incidence and mortality rate in females compared to males. This finding suggests a potential protective role of female steroid hormones, particularly estrogen, in the development of these cancers. Estrogen is a well-known sex hormone that not only regulates the reproductive system but also exerts diverse effects on non-reproductive organs mediated through interactions with estrogen receptors (ERs), including the classic (ERα and ERβ) and non-traditional ERs [G protein-coupled estrogen receptor (GPER)]. Recent advances have contributed to our comprehension of the mechanisms underlying ERs in digestive system cancers. In this comprehensive review we summarize the current understanding of the intricate roles played by estrogen and ERs in the major types of digestive system cancers, including hepatocellular, pancreatic, esophageal, gastric, and colorectal carcinoma. Furthermore, we discuss the potential molecular mechanisms underlying ERα, ERβ, and GPER effects, and propose perspectives on innovative therapies and preventive measures targeting the pathways regulated by estrogen and ERs. The roles of estrogen and ERs in digestive system cancers are complicated and depend on the cell type and tissue involved. Additionally, deciphering the intricate roles of estrogen, ERs, and the associated signaling pathways may guide the discovery of novel and tailored therapeutic and preventive strategies for digestive system cancers, eventually improving the care and clinical outcomes for the substantial number of individuals worldwide affected by these malignancies.</p>","PeriodicalId":9611,"journal":{"name":"Cancer Biology & Medicine","volume":"21 10","pages":""},"PeriodicalIF":5.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142543898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}