International Journal of Biological Sciences最新文献_第4页

BRD7 Inhibited Immune Escape in Nasopharyngeal Carcinoma via Inhibiting PD-L1 Expression.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-02-10 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.103703

Yilin Guo, Jiaxue Lu, Xiaoxu Li, Shiqi Yan, Jieyu Zhou, Ziying Tian, Ying Liu, Nan Li, Qing Zhou, Xiayu Li, Lei Shi, Su Jiang, Mengna Li, Xiao Zhou, Donghai Huang, Zhaoyang Zeng, Songqing Fan, Wei Xiong, Ming Zhou, Guiyuan Li, Wenling Zhang

{"title":"BRD7 Inhibited Immune Escape in Nasopharyngeal Carcinoma via Inhibiting PD-L1 Expression.","authors":"Yilin Guo, Jiaxue Lu, Xiaoxu Li, Shiqi Yan, Jieyu Zhou, Ziying Tian, Ying Liu, Nan Li, Qing Zhou, Xiayu Li, Lei Shi, Su Jiang, Mengna Li, Xiao Zhou, Donghai Huang, Zhaoyang Zeng, Songqing Fan, Wei Xiong, Ming Zhou, Guiyuan Li, Wenling Zhang","doi":"10.7150/ijbs.103703","DOIUrl":"10.7150/ijbs.103703","url":null,"abstract":"Therapeutic strategies aimed at harnessing anti-tumor immunity are being intensively investigated as they show promising results in cancer treatment. The PD-1/ PD-L1 pathway is an essential target for restoring functional anti-tumor immune response. BRD7 is a candidate tumor suppressor gene and nuclear transcription factor of nasopharyngeal carcinoma (NPC) which was cloned in our laboratory. In this paper, we reported that the candidate tumor suppressor gene BRD7 was strongly associated with good prognosis of NPC patients and negatively regulated PD-L1 expression. In addition, we found that BRD7 down-regulated PD-L1 expression and enhanced the killing function of CD8+ T lymphocytes in NPC cells through binding to p85α via the 485-651 domain and inhibiting the activity of PI3K, thereby inhibiting the activity of PI3K/AKT/mTOR/STAT3 pathway. In vivo experiments, the results showed that BRD7 could not only inhibit the growth of tumors, but also play a better anti-tumor effect when combined with PD-L1 antibody. These results provided further evidence that BRD7 inhibited immune escape of NPC through down-regulating PD-L1 expression.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 5","pages":"1914-1931"},"PeriodicalIF":8.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

METTL3-mediated m6A modification of SLC7A11 enhances nasopharyngeal carcinoma radioresistance by inhibiting ferroptosis.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-02-10 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.100518

Zili Dai, Baisheng Lin, Maohua Qin, Yunen Lin, Li Wang, Kai Liao, Guofeng Xie, Feixiang Wang, Jian Zhang

引用次数: 0

The Role of Mitochondrial Quality Control in Liver Diseases: Dawn of a Therapeutic Era.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-02-10 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.107777

Jia Li, Wenqin Liu, Jie Zhang, Chao Sun

{"title":"The Role of Mitochondrial Quality Control in Liver Diseases: Dawn of a Therapeutic Era.","authors":"Jia Li, Wenqin Liu, Jie Zhang, Chao Sun","doi":"10.7150/ijbs.107777","DOIUrl":"10.7150/ijbs.107777","url":null,"abstract":"The liver is a vital metabolic organ that detoxifies substances, produces bile, stores nutrients, and regulates versatile metabolic processes. Maintaining normal liver cell function requires the prompt and delicate modulation of mitochondrial quality control (MQC), which encompasses a spectrum of processes such as mitochondrial fission, fusion, biogenesis, and mitophagy. Recent studies have shown that disruptions to this homeostatic status are closely linked to the advent and progression of a variety of acute and chronic liver diseases, including but not limited to alcohol-associated liver disease and metabolic dysfunction-associated fatty liver disease. However, the explicit mechanisms by which mitochondrial dysfunction impacts inflammatory pathways and cell death in the context of liver diseases remain unclear. In this narrative review, we provide a detailed description of MQC, analyze the mechanisms underpinning mitochondrial dysfunction induced by different detrimental insults, and further elucidate how imbalanced/disrupted MQC promotes the progression and aggravation of liver diseases, ultimately shedding light on the mitochondrion-centric therapeutic strategies for these pathophysiological entities.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 4","pages":"1767-1783"},"PeriodicalIF":8.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fatty Acid Trafficking Between Lipid Droplets and Mitochondria: An Emerging Perspective.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-02-10 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.105361

Katarína Smolková, Klára Gotvaldová

{"title":"Fatty Acid Trafficking Between Lipid Droplets and Mitochondria: An Emerging Perspective.","authors":"Katarína Smolková, Klára Gotvaldová","doi":"10.7150/ijbs.105361","DOIUrl":"10.7150/ijbs.105361","url":null,"abstract":"The current understanding of lipid droplets (LDs) in cell biology has evolved from being viewed merely as storage compartments. LDs are now recognized as metabolic hubs that act as cytosolic buffers against the detrimental effects of free fatty acids (FAs). Upon activation, FAs traverse various cellular pathways, including oxidation in mitochondria, integration into complex lipids, or storage in triacylglycerols (TGs). Maintaining a balance among these processes is crucial in cellular FA trafficking, and under metabolically challenging circumstances the routes of FA metabolism adapt to meet the current cellular needs. This typically involves an increased demand for anabolic intermediates or energy and the prevention of redox stress. Surprisingly, LDs accumulate under certain conditions such as amino acid starvation. This review explores the biochemical aspects of FA utilization in both physiological contexts and within cancer cells, focusing on the metabolism of TGs, cholesteryl esters (CEs), and mitochondrial FA oxidation. Emphasis is placed on the potential toxicity associated with non-esterified FAs in cytosolic and mitochondrial compartments. Additionally, we discuss mechanisms that lead to increased LD biogenesis due to an inhibited mitochondrial import of FAs.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 5","pages":"1863-1873"},"PeriodicalIF":8.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11900811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143624500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Febuxostat therapy improved the outcomes of cardiorenal syndrome rodent through alleviating xanthine oxidase-induced oxidative stress and mitochondrial dysfunction.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-02-10 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.99194

Chih-Chao Yang, Ya Yue, Yi-Ling Chen, John Y Chiang, Yi-Ting Wang, Chi-Ruei Huang, Ben-Chung Cheng, Tsuen-Wei Hsu, Hon-Kan Yip

{"title":"Febuxostat therapy improved the outcomes of cardiorenal syndrome rodent through alleviating xanthine oxidase-induced oxidative stress and mitochondrial dysfunction.","authors":"Chih-Chao Yang, Ya Yue, Yi-Ling Chen, John Y Chiang, Yi-Ting Wang, Chi-Ruei Huang, Ben-Chung Cheng, Tsuen-Wei Hsu, Hon-Kan Yip","doi":"10.7150/ijbs.99194","DOIUrl":"10.7150/ijbs.99194","url":null,"abstract":"Background: We tested the hypothesis that febuxostat (Feb) therapy effectively protected cardiorenal syndrome (CRS) rats via repressing the xanthine-oxidase (XO)-caused oxidative stress. Methods and Results: Cellular levels of apoptosis/oxidative stress/mitochondrial-membrane potential were higher in p-Cresol treated-NRK-52E cells than in control group that were reversed by Feb treatment or silencing XO gene (all P<0.001). Pilot study demonstrated that: XO activity was significantly increased in CRS than in SC group; a significant negative correlation between XO activity and left ventricular ejection fraction (LVEF) (%); a significant positive correlation between XO activity and BNP/BUN/creatinine/proteinuria levels (all P<0.01). Male-adult SD-rats were classified into groups 1(sham-control)/2 (CRS)/3 [CRS+Feb (10mg/kg/day)]/4 [CRS+Feb (30mg/kg/day)]. By day-63, the survival rate was significantly lower in group 2 than in other groups (P=0.029), and circulatory levels of FGF23/BNP/XO-activity BUN/creatinine/proteinuria and renal-artery resistance were highest in group 2/lowest in group 1/significantly lower in group 4 than in group 3, whereas the LVEF exhibited an opposite pattern of XO among the groups (all P<0.0001). Cellular levels of fibrosis/XO/H2DCFDA/CD68/CHAC1, and protein expressions of oxidative-stress (NOX-2/NOX-4/XO)/inflammatory (NF-κB/IL-1β)/fibrotic (Smad3/TFG-β)/apoptotic (CHAC1/2)/mitochondrial-damaged (p-DRP1) biomarkers in kidney/heart tissues displayed a similar pattern of XO (all P<0.0001). Conclusion: Feb therapy improved cardiorenal function and prognostic outcome in CRS rats.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 4","pages":"1749-1766"},"PeriodicalIF":8.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The E3 ubiquitin ligase MAEA promotes macrophage phagocytosis and inhibits gastrointestinal cancer progression by mediating PARP1 ubiquitination and degradation.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-02-10 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.102796

Yanchun Feng, Xiangcai Zou, Jintuan Huang, Zhenze Huang, Guanghao Kuang, Yingming Jiang

{"title":"The E3 ubiquitin ligase MAEA promotes macrophage phagocytosis and inhibits gastrointestinal cancer progression by mediating PARP1 ubiquitination and degradation.","authors":"Yanchun Feng, Xiangcai Zou, Jintuan Huang, Zhenze Huang, Guanghao Kuang, Yingming Jiang","doi":"10.7150/ijbs.102796","DOIUrl":"10.7150/ijbs.102796","url":null,"abstract":"Background: While a role for the E3 ubiquitin ligase MAEA (macrophage erythroblast attacher) has been reported in several cancer types, its importance and mechanistic functions in gastrointestinal cancer (GIC) have yet to be established. Methods: The functions of MAEA in GIC were explored through in vitro and in vivo experiments, including loss- and gain-of-function analyses. Mass spectrometry was used to identify proteins that interact with MAEA. The mechanisms through which MAEA influences tumor aggression were examined through immunoprecipitation analyses. Results: GIC patients exhibiting reduced expression of MAEA were found to exhibit worse disease-free and overall survival outcomes. MAEA was found to impair the proliferation and chemoresistance of GIC tumors in vitro and in subcutaneous xenograft model systems. The combination of MAEA and the PARP1 inhibitor veliparib resulted in enhanced oxaliplatin treatment efficacy in vivo. From a mechanistic perspective, MAEA was found to mediate the K48-linked ubiquitination and degradation of PARP1, in addition to suppressing the M2 polarization of macrophages and enhancing macrophage phagocytic activity. Conclusions: These data suggest that MAEA offers value as a prognostic biomarker and target for the treatment of GIC owing to its ability to degrade PARP1 and augment the phagocytic activity of macrophages.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 4","pages":"1784-1800"},"PeriodicalIF":8.2,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modulation of TGF-β signaling new approaches toward kidney disease and fibrosis therapy.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-02-03 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.101548

Quan Hong, Hyoungnae Kim, Guang-Yan Cai, Xiang-Mei Chen, John Cijiang He, Kyung Lee

{"title":"Modulation of TGF-β signaling new approaches toward kidney disease and fibrosis therapy.","authors":"Quan Hong, Hyoungnae Kim, Guang-Yan Cai, Xiang-Mei Chen, John Cijiang He, Kyung Lee","doi":"10.7150/ijbs.101548","DOIUrl":"10.7150/ijbs.101548","url":null,"abstract":"The prevalence of chronic kidney disease (CKD) is increasing worldwide, posing a significant healthcare challenge. Despite the immense burden of CKD, optimal therapies remain limited in impact. Kidney fibrosis is a common mediator of all CKD progression, characterized by excessive extracellular matrix deposition and scarring of kidney parenchyma. Transforming growth factor-β (TGF-β) is a potent pro-fibrotic cytokine that signals through canonical and non-canonical pathways to promote kidney cell damage and fibrosis progression, thus garnering much interest as an optimal therapeutic target for CKD. However, the clinical translation of TGF-β inhibition in CKD and other disease settings has faced substantial challenges, particularly due to the highly pleiotropic effects of TGF-β in organ homeostasis and disease. Here, we review the kidney cell-specific biological effects of TGF-β signaling, discuss the current challenges in therapeutic targeting TGF-β in CKD, and provide the rationale for alternative targeting strategies of TGF-β signaling as potential approaches in CKD therapy. Selective inhibition of TGF-β signaling modulators to fine-tune TGF-β inhibition without a broad blockade may lead to new and safer treatments for CKD.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 4","pages":"1649-1665"},"PeriodicalIF":8.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antibody-dependent enhancement of coronaviruses.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-02-03 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.96112

Tao Tao, Lili Tian, Jiayi Ke, Chuxie Zhang, Maochen Li, Xiaolong Xu, Junfen Fan, Yigang Tong, Huahao Fan

{"title":"Antibody-dependent enhancement of coronaviruses.","authors":"Tao Tao, Lili Tian, Jiayi Ke, Chuxie Zhang, Maochen Li, Xiaolong Xu, Junfen Fan, Yigang Tong, Huahao Fan","doi":"10.7150/ijbs.96112","DOIUrl":"10.7150/ijbs.96112","url":null,"abstract":"The COVID-19 pandemic presents a significant challenge to the global health and the world economy, with humanity engaged in an extended struggle against the virus. Notable advancements have been achieved in the development of vaccines and therapeutic interventions, including the application of neutralizing antibodies (NAbs) and convalescent plasma (CP). While antibody-dependent enhancement (ADE) has not been observed in human clinical studies related to SARS-CoV-2, the potential for ADE remains a critical concern and challenge in addressing SARS-CoV-2 infections. Moreover, the causal relationship between ADE and viral characteristics remains to be clearly elucidated. Viruses that present with severe clinical manifestations of ADE have demonstrated the capacity to replicate in macrophages or other immune cells, or to alter the immunological status of these cells, which induces abortive infections characterized by systemic inflammation. In this review, we summarize experimental observations and clinical evidence concerning the ADE effect associated with coronaviruses. We critically examine the potential mechanisms through which coronaviruses mediate ADE, and propose strategies to mitigate this phenomenon in the context of viral infection treatment. Our aim is to offer informed recommendations for the containment of the COVID-19 pandemic and to strengthen the response to SARS-CoV-2, as well as to prepare for potential future coronavirus threats.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 4","pages":"1686-1704"},"PeriodicalIF":8.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

BCLAF1 Regulates Osteoarthritic Cartilage Degradation Through Interaction with LAMTOR2.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-02-03 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.100396

Song Li, Danni Luo, Yulin Liang, Yi Zou, Hongxu Pu, Meng Zheng, Yuting Wang, Xuying Sun, Hao Zhu, Yuanli Zhu, Liming Zhao, Jun Xiao

{"title":"BCLAF1 Regulates Osteoarthritic Cartilage Degradation Through Interaction with LAMTOR2.","authors":"Song Li, Danni Luo, Yulin Liang, Yi Zou, Hongxu Pu, Meng Zheng, Yuting Wang, Xuying Sun, Hao Zhu, Yuanli Zhu, Liming Zhao, Jun Xiao","doi":"10.7150/ijbs.100396","DOIUrl":"10.7150/ijbs.100396","url":null,"abstract":"Osteoarthritis (OA) is a progressive degenerative joint disorder with cartilage degradation as the primary cause of joint pain and loss of joint function. B-cell lymphoma-2-associated transcription factor 1 (BCLAF1) is a key regulator of apoptosis and serves as a signal transducer of the NFκB and Hif-1α pathways, both of which are involved in osteoarthritic cartilage degradation. However, whether BCLAF1 contributes to the pathogenesis of OA remains unclear. The present study aims to elucidate the role of BCLAF1 in osteoarthritic cartilage degradation and the underlying mechanisms. We found that BCLAF1 levels were increased in cartilage tissue from OA patients, elder and surgery-induced OA mice, and primary chondrocytes treated with inflammatory cytokines. Knockdown of Bclaf1 in chondrocytes inhibited the expression of catabolic factors and apoptosis rate, while promoting the expression of anabolic factors and enhancing chondrocyte functions such as viability and migration. Conversely, overexpression of Bclaf1 produced the opposite effects. Furthermore, intra-articular injection of adenovirus containing shRNA targeting Bclaf1 attenuated cartilage degradation and osteophytosis in a mouse OA model, while overexpression of BCLAF1 further aggravated cartilage degradation and osteophytosis in vivo. Through immunoprecipitation and protein mass spectrometry, we identified LAMTOR2 as a key mediator of BCLAF1 by regulating the translocation of BCLAF1 into the nucleus. Our findings reveal the critical role and key mechanisms of BCLAF1 in regulating cartilage degradation, representing a novel molecular target for the therapeutic development of OA.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 4","pages":"1666-1685"},"PeriodicalIF":8.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Disulfiram/copper triggers cGAS-STING innate immunity pathway via ROS-induced DNA damage that potentiates antitumor response to PD-1 checkpoint blockade.

IF 8.2 2区生物学

International Journal of Biological Sciences Pub Date : 2025-02-03 eCollection Date: 2025-01-01 DOI: 10.7150/ijbs.105575

Mengmeng Yuan, Liang Shi, Yan Liu, Ke Xiang, Yan Zhang, Ye Zhou, Jianling Wang, Meiju Ji, Peng Hou

{"title":"Disulfiram/copper triggers cGAS-STING innate immunity pathway via ROS-induced DNA damage that potentiates antitumor response to PD-1 checkpoint blockade.","authors":"Mengmeng Yuan, Liang Shi, Yan Liu, Ke Xiang, Yan Zhang, Ye Zhou, Jianling Wang, Meiju Ji, Peng Hou","doi":"10.7150/ijbs.105575","DOIUrl":"10.7150/ijbs.105575","url":null,"abstract":"Immune checkpoint blockades (ICBs) have emerged as the leading strategy for treating advanced malignancies; however, their clinical efficacy is frequently constrained by primary or acquired resistance. Harnessing innate immune signaling to increase lymphocyte infiltration into tumors has been recognized a promising approach to augment the anti-cancer immune response to ICBs. Disulfiram (DSF), an FDA-approved drug for chronic alcoholism, has shown potent anti-tumor effect, particularly when used in combination with copper (Cu). Here, we demonstrated a combination treatment of DSF and Cu (DSF/Cu) robustly activated cancer cell-intrinsic cGAS-STING-dependent innate immune signaling pathway. Further studies revealed that DSF/Cu caused mitochondrial and nuclear DNA damage and the release of cytosolic dsDNA by inducing excessive reactive oxygen species (ROS) generation, thereby triggering innate immunity and enhancing anti-tumor effects. Moreover, DSF/Cu significantly increased the intratumoral infiltration of CD8+ cytotoxic lymphocytes and natural killer (NK) cells, and potentiated the therapeutic efficacy of PD-1 checkpoint blockade in murine tumor models. Overall, our findings provide a rationale underlying the anti-cancer and immunomodulatory function of DSF/Cu and highlight the potential of repurposing DSF to improve responses to ICBs in cancer patients.","PeriodicalId":13762,"journal":{"name":"International Journal of Biological Sciences","volume":"21 4","pages":"1730-1748"},"PeriodicalIF":8.2,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11844283/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0