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Predicting response to PD-1 inhibitors in head and neck squamous cell carcinomas using peripheral blood inflammatory markers
IF 5 2区 医学
Translational Oncology Pub Date : 2024-12-01 DOI: 10.1016/j.tranon.2024.102222
Ruihua Fang , Yi Chen , Bixue Huang , Zhangfeng Wang , Xiaolin Zhu , Dawei Liu , Wei Sun , Lin Chen , Minjuan Zhang , Kexing Lyu , Wenbin Lei
{"title":"Predicting response to PD-1 inhibitors in head and neck squamous cell carcinomas using peripheral blood inflammatory markers","authors":"Ruihua Fang ,&nbsp;Yi Chen ,&nbsp;Bixue Huang ,&nbsp;Zhangfeng Wang ,&nbsp;Xiaolin Zhu ,&nbsp;Dawei Liu ,&nbsp;Wei Sun ,&nbsp;Lin Chen ,&nbsp;Minjuan Zhang ,&nbsp;Kexing Lyu ,&nbsp;Wenbin Lei","doi":"10.1016/j.tranon.2024.102222","DOIUrl":"10.1016/j.tranon.2024.102222","url":null,"abstract":"<div><div>Immune checkpoint inhibitor (ICI) treatment has the potential to induce durable disease remission. However, the current combined positive score (CPS) is insufficient accurate for predicting which patients will benefit from it. In the present study, a real-world retrospective study was conducted on 56 patients of HNSCC who received ICI treatment. Then the treatment that patient received and levels of pre-treatment blood inflammatory markers (NLR, MLR and PLR) were identified to develop a model for predicting immunotherapy response. Notably, the model achieved an area under the curve (AUC) of 0.877 (95 % CI 0.769–0.985) , providing a larger net benefit than the CPS marker (AUC=0.614, 95 % CI 0.466–0.762). Furthermore, the internal validation of the prediction model showed a C-index of 0.835. Patients with high score of the model would get improved PFS than those with low score. Therefore, the prediction model for patients with local advanced or R/M HNSCC receiving ICI treatment, which represented an better efficient prediction of immunotherapy response than CPS marker.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102222"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757280","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}
引用次数: 0
Patient-derived tumor organoids: A preclinical platform for personalized cancer therapy
IF 5 2区 医学
Translational Oncology Pub Date : 2024-12-01 DOI: 10.1016/j.tranon.2024.102226
Sebastien Taurin, Reem Alzahrani, Sahar Aloraibi, Layal Ashi, Rawan Alharmi, Noora Hassani
{"title":"Patient-derived tumor organoids: A preclinical platform for personalized cancer therapy","authors":"Sebastien Taurin,&nbsp;Reem Alzahrani,&nbsp;Sahar Aloraibi,&nbsp;Layal Ashi,&nbsp;Rawan Alharmi,&nbsp;Noora Hassani","doi":"10.1016/j.tranon.2024.102226","DOIUrl":"10.1016/j.tranon.2024.102226","url":null,"abstract":"<div><div>Patient-derived tumor organoids (PDTOs) represent a significant advancement in cancer research and personalized medicine. These organoids, derived from various cancer types, have shown the ability to retain the genetic and molecular characteristics of the original tumors, allowing for the detailed study of tumor biology and drug responses on an individual basis. The success rates of establishing PDTOs vary widely and are influenced by factors such as cancer type, tissue quality, and media composition. Furthermore, the dynamic nature of organoid cultures may also lead to unique molecular characteristics that deviate from the original tumors, affecting their interpretation in clinical settings without the implementation of rigorous validation and establishment of standardized protocols. Recent studies have supported the correlation between PDTOs and the corresponding patient response. Although these studies involved a small number of patients, they promoted the integration of PDTOs in observational and interventional clinical trials to advance translational cancer therapies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102226"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757261","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}
引用次数: 0
Molecular profiling of head and neck squamous cell carcinomas in North-eastern Italy identifies possible tumour cell vulnerabilities
IF 5 2区 医学
Translational Oncology Pub Date : 2024-12-01 DOI: 10.1016/j.tranon.2024.102221
Monica Schiappacassi , Riccardo Spizzo , Jerry Polesel , Lorena Musco , Roberto Doliana , Luca Pellizzari , Valentina Lupato , Giuseppe Fanetti , Emanuela Vaccher , Diego Serraino , Luigi Barzan , Sandro Sulfaro , Vittorio Giacomarra , Giovanni Franchin , Gustavo Baldassarre
{"title":"Molecular profiling of head and neck squamous cell carcinomas in North-eastern Italy identifies possible tumour cell vulnerabilities","authors":"Monica Schiappacassi ,&nbsp;Riccardo Spizzo ,&nbsp;Jerry Polesel ,&nbsp;Lorena Musco ,&nbsp;Roberto Doliana ,&nbsp;Luca Pellizzari ,&nbsp;Valentina Lupato ,&nbsp;Giuseppe Fanetti ,&nbsp;Emanuela Vaccher ,&nbsp;Diego Serraino ,&nbsp;Luigi Barzan ,&nbsp;Sandro Sulfaro ,&nbsp;Vittorio Giacomarra ,&nbsp;Giovanni Franchin ,&nbsp;Gustavo Baldassarre","doi":"10.1016/j.tranon.2024.102221","DOIUrl":"10.1016/j.tranon.2024.102221","url":null,"abstract":"<div><h3>Background and Purpose</h3><div>Head and Neck Squamous Cell Cancer (HNSCC) originates from the oral cavity, oropharynx, hypopharynx and larynx, and it ranks sixth among global cancers. Despite modest 5-year survival gains, the integration of molecular personalization lags behind and there is an urgent need to develop novel therapies and biomarkers.</div></div><div><h3>Material and Methods</h3><div>This study outlined the somatic mutational profile of 15 HNSCC-enriched genes in a case series from North-eastern Italy, the region with the highest national HNSCC incidence. We conducted a comparative analysis with prior case studies and assessed the prognostic implications of the mutations that we found in these genes.</div></div><div><h3>Results</h3><div>Consistent with previous studies, oral cavity tumours showed a lower gene mutation frequency. We highlighted a significant enrichment of somatic <em>AJUBA</em> mutations in the hypopharyngeal region, linked to a poorer prognosis. Moreover, <em>KMT2C</em> mutations co-occurring with <em>CDKN2A</em> or <em>NOTCH1</em> mutations were associated with a worse prognosis. At the same time, only 7 % of the cases exhibited mutations that are predictive biomarker in HNSCC according to compelling clinical evidence but that need further investigation in a clinical trial setting.</div></div><div><h3>Conclusion</h3><div>Our findings underlined novel differences in somatic gene mutations among the four anatomic sites. However, at present, the identified mutations cannot yet be considered predictive biomarkers either for the lack of supporting clinical findings or for the lack of approved targeted therapies in HNSCC. This underscores the imperative for continued investigation into the biology of HNSCC to unveil novel vulnerabilities that can be leveraged to enhance patient treatment strategies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102221"},"PeriodicalIF":5.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757262","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}
引用次数: 0
O-GlcNAcylation in ovarian tumorigenesis and its therapeutic implications
IF 5 2区 医学
Translational Oncology Pub Date : 2024-11-30 DOI: 10.1016/j.tranon.2024.102220
Lu Xia, Jie Mei, Min Huang, Dandan Bao, Zhiwei Wang, Yizhe Chen
{"title":"O-GlcNAcylation in ovarian tumorigenesis and its therapeutic implications","authors":"Lu Xia,&nbsp;Jie Mei,&nbsp;Min Huang,&nbsp;Dandan Bao,&nbsp;Zhiwei Wang,&nbsp;Yizhe Chen","doi":"10.1016/j.tranon.2024.102220","DOIUrl":"10.1016/j.tranon.2024.102220","url":null,"abstract":"<div><div>Ovarian cancer is a prevalent malignancy among women, often associated with a poor prognosis. Post-translational modifications (PTMs), particularly O-GlcNAcylation, have been implicated in the progression of ovarian cancer. Emerging evidence indicates that dysregulation of O-GlcNAcylation contributes to the initiation and malignant progression of ovarian cancer. This review discusses the potential role of O-GlcNAcylation in ovarian tumorigenesis, with a focus on its regulation of various cellular signaling pathways, including p53, RhoA/ROCK/MLC, Ezrin/Radixin/Moesin (ERM), and β-catenin. This review also emphasizes the O-GlcNAcylation of critical proteins in ovarian cancer, such as SNAP-23, SNAP-29, E-cadherin, and calreticulin. Additionally, the potential of O-GlcNAcylation to enhance immunotherapy for ovarian cancer patients is explored. Several compounds targeting OGT and OGA in ovarian cancer are also highlighted. Targeting the dynamic and versatile nature of O-GlcNAcylation could undoubtedly contribute to more effective treatments and improved outcomes for ovarian cancer patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102220"},"PeriodicalIF":5.0,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745093","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}
引用次数: 0
SIRT5 inhibits glycolysis and nasal type extranodal NK/T cell lymphoma cell proliferation by catalyzing the desuccinylation of glucose-6-phosphate isomerase
IF 5 2区 医学
Translational Oncology Pub Date : 2024-11-29 DOI: 10.1016/j.tranon.2024.102215
Tiansheng Wang , Guolin Tan , Ming Jiang , Guohui Liu , Wei Li , Xiang Qing
{"title":"SIRT5 inhibits glycolysis and nasal type extranodal NK/T cell lymphoma cell proliferation by catalyzing the desuccinylation of glucose-6-phosphate isomerase","authors":"Tiansheng Wang ,&nbsp;Guolin Tan ,&nbsp;Ming Jiang ,&nbsp;Guohui Liu ,&nbsp;Wei Li ,&nbsp;Xiang Qing","doi":"10.1016/j.tranon.2024.102215","DOIUrl":"10.1016/j.tranon.2024.102215","url":null,"abstract":"<div><h3>Background</h3><div>Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is a malignant tumor harboring a poor prognosis and unsatisfactory treatment outcomes. This study was performed to explore the pathogenesis and exact etiology of ENKTL. <strong>Methods</strong> Bioinformatic analysis was conducted to investigate the expression of SIRT5 and glucose-6-phosphate isomerase (GPI), as well their correlation with ENKTL overall survival. Cell proliferation ability and cell apoptosis were determined by CCK8, soft-agar colony formation and Tunel assays. Pyruvic acid and lactate production, GPI activity and F6P levels were detected to indicate glycolysis process. Succinylation modification in GPI protein was quantified by 4D label-free succinylation modification quantitative proteome. ENKTL mouse model was established by the injection of SNK6 cells.</div></div><div><h3>Results</h3><div>SIRT5 suppressed the NKTL cell proliferation through the desuccinylation effect, while it was down-regulated in the ENKTL. SIRT5 catalyzed the desuccinylation of glycolytic enzyme GPI in ENKTL cells, which accelerated GPI protein degradation through the autophagy-lysosome system. SIRT5 inhibited glycolysis via mediating the desuccinylation of GPI, thereby suppressing ENKTL cell proliferation. The antitumor role of SIRT5 was also certified in ENKTL mouse model by targeting GPI.</div></div><div><h3>Conclusion</h3><div>SIRT5 inhibits glycolysis via catalyzed the desuccinylation of glycolytic enzyme GPI, thereby repressing ENKTL cells proliferation and tumor growth. As SIRT5 serves as a tumor suppressor in ENKTL, it may be a promising molecular target in therapy strategy.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102215"},"PeriodicalIF":5.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745033","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}
引用次数: 0
Exploring the tumor-suppressive role of miRNA-200c in head and neck squamous cell carcinoma: Potential and mechanisms of exosome-mediated delivery for therapeutic applications
IF 5 2区 医学
Translational Oncology Pub Date : 2024-11-29 DOI: 10.1016/j.tranon.2024.102216
Mohamed S. Kishta , Aya Khamis , Hafez AM , Abdelrahman H. Elshaar , Désirée Gül
{"title":"Exploring the tumor-suppressive role of miRNA-200c in head and neck squamous cell carcinoma: Potential and mechanisms of exosome-mediated delivery for therapeutic applications","authors":"Mohamed S. Kishta ,&nbsp;Aya Khamis ,&nbsp;Hafez AM ,&nbsp;Abdelrahman H. Elshaar ,&nbsp;Désirée Gül","doi":"10.1016/j.tranon.2024.102216","DOIUrl":"10.1016/j.tranon.2024.102216","url":null,"abstract":"<div><div>Head and neck squamous cell carcinoma (HNSCC) remains a challenging malignancy due to its high rates of recurrence, metastasis, and resistance to conventional therapies. microRNA-200c (miRNA-200c) has emerged as a critical tumor suppressor in HNSCC, with the potential to inhibit epithelial-mesenchymal transition (EMT), which is considered as a key process in cancer metastasis and progression. Interestingly, there are also controversial findings in HNSCC characterizing miRNA-200c as oncogenic factor. This review article provides a comprehensive overview of the current understanding of miRNA-200c's general role in cancer, and particularly in HNSCC, highlighting its mechanisms of action, including the regulation of EMT and other oncogenic pathways.</div><div>Additionally, the review explores the innovative approach of exosome-mediated delivery of miRNA-200c as a therapeutic strategy. Exosomes, as natural nanocarriers, offer a promising vehicle for the targeted delivery of miRNA-200c to tumor cells, potentially overcoming the limitations of traditional delivery methods and enhancing therapeutic efficacy. The review also discusses the challenges and future directions in the clinical application of miRNA-200c, particularly focusing on its potential to improve outcomes for HNSCC patients. This article seeks to provide valuable insights for researchers and clinicians working towards innovative treatments for this aggressive cancer type.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102216"},"PeriodicalIF":5.0,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745092","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}
引用次数: 0
FLASH radiotherapy combined with immunotherapy: From biological mechanisms to blockbuster therapeutics
IF 5 2区 医学
Translational Oncology Pub Date : 2024-11-28 DOI: 10.1016/j.tranon.2024.102183
Yu Wang , Shu-Nan Qi , Nan Bi , Ye-Xiong Li
{"title":"FLASH radiotherapy combined with immunotherapy: From biological mechanisms to blockbuster therapeutics","authors":"Yu Wang ,&nbsp;Shu-Nan Qi ,&nbsp;Nan Bi ,&nbsp;Ye-Xiong Li","doi":"10.1016/j.tranon.2024.102183","DOIUrl":"10.1016/j.tranon.2024.102183","url":null,"abstract":"<div><div>FLASH ultra-high dose rate radiotherapy (RT) can effectively exert the protective effect on normal tissue and reduce the risk of treatment-related toxicity, without compromising the killing effect on tumor tissue, resulting in a significant differential biological effect between tumor control and normal tissue damage, namely the FLASH effect. To date, the precise biological details of the FLASH effect remain uncertain. The currently mainstream mechanisms proposed by the academic community include the transient oxygen depletion hypothesis, free radical hypothesis, immune protection hypothesis, and DNA integrity hypothesis, which have attracted increasing attention in recent years. Based on these theoretical principles and numerous investigations on the FLASH effect in vivo and in vitro, the combined application of FLASH and immune checkpoint inhibitors (ICIs) has been considered synergistic and potentially practical. The primary underlying basis is that FLASH might actively preserve the number and function of circulating immune cells, thereby enhancing the efficacy of immune cell-mediated immunotherapy. Meanwhile, FLASH RT could activate the tumor immune microenvironment and transform \"cold'' tumors into ''hot'' ones, consequently boosting local and systemic anti-tumor immunity and expanding the therapeutic benefits of ICIs. Moreover, FLASH might attenuate immunoinflammatory responses and minimize the incidence of radiation-related adverse events, allowing for the potentially safer and promising clinical application of combing FLASH RT with ICI therapy. Nevertheless, data on this treatment modality is currently lacking, and several barriers remain to be addressed, including the logistical bottlenecks, technical hurdles, limited availability, and unclear biological mechanisms. Further research is warranted in the future.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102183"},"PeriodicalIF":5.0,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745091","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}
引用次数: 0
MYST2 histone acetyltransferase promotes lung adenocarcinoma progression by regulating the p38 MAPK signaling pathway MYST2 组蛋白乙酰转移酶通过调节 p38 MAPK 信号通路促进肺腺癌的进展
IF 5 2区 医学
Translational Oncology Pub Date : 2024-11-27 DOI: 10.1016/j.tranon.2024.102218
Zhiang Huang , Wanru Zhang , Ping Wang , Mengyao Wu , Yipu Guo , Jingying Chen
{"title":"MYST2 histone acetyltransferase promotes lung adenocarcinoma progression by regulating the p38 MAPK signaling pathway","authors":"Zhiang Huang ,&nbsp;Wanru Zhang ,&nbsp;Ping Wang ,&nbsp;Mengyao Wu ,&nbsp;Yipu Guo ,&nbsp;Jingying Chen","doi":"10.1016/j.tranon.2024.102218","DOIUrl":"10.1016/j.tranon.2024.102218","url":null,"abstract":"<div><h3>Background</h3><div>Lung cancer, particularly lung adenocarcinoma, poses a significant health challenge due to its high incidence and mortality rates. Despite advancements in targeted therapies, treatment outcomes for lung adenocarcinoma remain unsatisfactory. This study explores the role of the histone acetyltransferase MYST2 in lung adenocarcinoma and its potential as a therapeutic target.</div></div><div><h3>Methods</h3><div>An analysis using the TIMER 2.0 and TCGA databases was performed to compare the expression levels of MYST2 between lung adenocarcinoma tissues and normal tissues. Functional assays, including cell proliferation, migration, and invasion, were conducted to evaluate the effects of MYST2 overexpression and knockout in lung cancer cells. Co-immunoprecipitation and GST pull-down assays were utilized to identify interactions involving the MYST domain of MYST2 and p38, while also assessing the impact of MYST2 on the binding between MEK6 and p38.</div></div><div><h3>Results</h3><div>The analysis revealed that MYST2 was significantly up-regulated in lung adenocarcinoma tissues compared to normal tissues and was associated with poor prognosis. Functional assays demonstrated that MYST2 overexpression promoted, whereas MYST2 knockout inhibited, lung cancer cell proliferation, migration, and invasion. Mechanistically, MYST2 enhanced the phosphorylation of p38 and ERK. Co-immunoprecipitation and GST pull-down assays identified the MYST domain of MYST2 as crucial for its interaction with p38. Additionally, MYST2 overexpression facilitated the binding of MEK6 to p38, indirectly influencing p38 activity.</div></div><div><h3>Conclusion</h3><div>These findings suggest that MYST2 acts as an oncogene in lung cancer by modulating p38 phosphorylation through the MYST domain, underscoring its potential as a prognostic marker and therapeutic target.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102218"},"PeriodicalIF":5.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720020","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}
引用次数: 0
Immunogenic clearance combined with PD-1 blockade elicits antitumor effect by promoting the recruitment and expansion of the effector memory-like CD8+ T cell 免疫原性清除与 PD-1 阻断相结合,通过促进效应记忆型 CD8+ T 细胞的招募和扩增而产生抗肿瘤效果
IF 5 2区 医学
Translational Oncology Pub Date : 2024-11-27 DOI: 10.1016/j.tranon.2024.102209
Seong A Kim , Seohyun Kim , Yeonsun Hong , Yoonjeong Choi , Yeji Lee , Minsu Kwon , Seung-Yoon Park , Cherlhyun Jeong , Gi-Hoon Nam , Rafael T. Han , In-San Kim
{"title":"Immunogenic clearance combined with PD-1 blockade elicits antitumor effect by promoting the recruitment and expansion of the effector memory-like CD8+ T cell","authors":"Seong A Kim ,&nbsp;Seohyun Kim ,&nbsp;Yeonsun Hong ,&nbsp;Yoonjeong Choi ,&nbsp;Yeji Lee ,&nbsp;Minsu Kwon ,&nbsp;Seung-Yoon Park ,&nbsp;Cherlhyun Jeong ,&nbsp;Gi-Hoon Nam ,&nbsp;Rafael T. Han ,&nbsp;In-San Kim","doi":"10.1016/j.tranon.2024.102209","DOIUrl":"10.1016/j.tranon.2024.102209","url":null,"abstract":"<div><div>Immune checkpoint inhibition shows promise for cancer treatment, but only a minority of patients respond. Combination strategies have been explored to overcome this resistance. Combining immunogenic clearance using immunogenic cell death inducers with a rho kinase inhibitor enhances phagocytosis of immunogenically dying cancer cells by antigen-presenting cells, stimulating tumor-specific immune responses by activating CD8<strong><sup>+</sup></strong> <em>T</em> cells via dendritic cell-mediated priming. This approach increases the responsiveness of immune checkpoint blockade (ICB)-resistant cancer to ICB. However, the precise mechanisms remain unclear. This study elucidates cellular mechanisms of immunogenic clearance enhancing ICB response. Using single-cell RNA sequencing, we observed an increase in effector memory-like CD8<strong><sup>+</sup></strong> <em>T</em> cells within the tumor microenvironment with combined treatment. We propose this cell cluster may originate from proliferating CD8<strong><sup>+</sup></strong> <em>T</em> cells elevated by immunogenic clearance. Notably, abundant effector memory-like CD8<strong><sup>+</sup></strong> <em>T</em> cells in ICB-responsive patients suggest their antitumor effect. Thus, increasing this cell population through enhanced T cell priming may improve the response of ICB-resistant tumors.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102209"},"PeriodicalIF":5.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720014","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}
引用次数: 0
Mendelian randomization and transcriptomic analysis reveal a positive cause-and-effect relationship between Alzheimer's disease and colorectal cancer 孟德尔随机化和转录组分析揭示了阿尔茨海默病与结直肠癌之间的正向因果关系
IF 5 2区 医学
Translational Oncology Pub Date : 2024-11-27 DOI: 10.1016/j.tranon.2024.102169
Wei Du , Xueming Xia , Qiheng Gou , Yan Qiu
{"title":"Mendelian randomization and transcriptomic analysis reveal a positive cause-and-effect relationship between Alzheimer's disease and colorectal cancer","authors":"Wei Du ,&nbsp;Xueming Xia ,&nbsp;Qiheng Gou ,&nbsp;Yan Qiu","doi":"10.1016/j.tranon.2024.102169","DOIUrl":"10.1016/j.tranon.2024.102169","url":null,"abstract":"<div><h3>Background</h3><div>This study addresses the complex multifactorial causes of Alzheimer's disease (AD) and colorectal cancer (CRC), two significant public health issues. Despite previous research, the precise relationship between AD and CRC remains unclear. This study aimed to explore the potential causal relationship between AD and CRC using Mendelian randomization (MR) and to identify risk genes through colocalization and transcriptomic analyses.</div></div><div><h3>Method</h3><div>The study used a two-sample Mendelian randomization (MR) approach to investigate the causal effect of AD on CRC. Genome-wide association study (GWAS) summary statistics for AD and CRC were utilized. Colocalization analysis was conducted to identify risk genes associated with AD, which were then validated through transcriptomic analysis in CRC samples. The study used GWAS data from a cohort of European patients and applied several MR methods, including MR Egger, weighted median, and inverse-variance weighted approaches, to ensure robust findings.</div></div><div><h3>Results</h3><div>The MR analysis revealed a significant positive causal relationship between AD and CRC, indicating that an increased genetic predisposition to AD is associated with a elevated risk of developing CRC. The colocalization analysis identified <em>COLEC11</em> as a significant risk gene for AD, which also showed a strong positive correlation with clinical features and survival outcomes in CRC. Elevated <em>COLEC11</em> expression was linked to advanced clinical stages, increased tumor mutational burden, microsatellite instability, and poorer overall survival in CRC patients.</div></div><div><h3>Conclusions</h3><div>This study provides evidence of a causal relationship between AD and CRC, suggesting that shared genetic and inflammatory pathways may underlie both conditions. The identification of <em>COLEC11</em> as a potential link between AD and CRC offers new avenues for research and therapeutic interventions. These findings contribute to a deeper understanding of the interplay between neurodegenerative and oncologic diseases, highlighting the importance of exploring common pathogenic mechanisms.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"51 ","pages":"Article 102169"},"PeriodicalIF":5.0,"publicationDate":"2024-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142719878","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}
引用次数: 0
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