Translational Oncology最新文献

Universal CAR cell therapy: Challenges and expanding applications 通用 CAR 细胞疗法：挑战与应用拓展

IF 5 2区医学

Translational Oncology Pub Date : 2024-10-15 DOI: 10.1016/j.tranon.2024.102147

{"title":"Universal CAR cell therapy: Challenges and expanding applications","authors":"","doi":"10.1016/j.tranon.2024.102147","DOIUrl":"10.1016/j.tranon.2024.102147","url":null,"abstract":"<div><div>Chimeric Antigen Receptor (CAR) T cell therapy has gained success in adoptive cell therapy for hematological malignancies. Although most CAR cell therapies in clinical trials or markets remain autologous, their acceptance has been limited due to issues like lengthy manufacturing, poor cell quality, and demanding cost. Consequently, “Off-the-shelf”, universal CAR (UCAR) cell therapy has emerged. Current concerns with UCAR therapies revolve around side effects such as graft versus host disease (GVHD) and host versus graft response (HVGR). Preclinical research on UCAR cell therapies aims to enhance efficacy and minimize these side effects. Common approaches involve gene editing techniques to knock out T cell receptor (TCR), human leukocyte antigen (HLA), and CD52 expression to mitigate GVHD and HVGR risks. However, these methods carry drawbacks including potential genotoxicity of the edited cells. Most recently, novel editing techniques, such as epigenetic editing and RNA writer systems, have been developed to reduce the risk of GVHD and HVGR, allowing for multiplex editing at different sites. Additionally, incorporating more cell types into UCAR cell therapies, like T-cell subtypes (DNT, γδT, virus-specific T cells) and NK cells, can efficiently target tumors without triggering side effects. In addition, the limited efficacy of T cells and NK cells against solid tumors is being addressed through CAR-Macrophages. In summary, CAR cell therapy has evolved to accommodate multiple cell types while expanding applications to various diseases, including hematologic malignancies and solid tumors, which holds tremendous growth potential and is promised to improve the lives of more patients in the future.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142432753","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

High circulating activin A plasma levels are associated with tumour stage and poor survival in treatment-naive lung squamous cell cancer patients 循环激活素 A 血浆水平高与肿瘤分期和未经治疗的肺鳞癌患者生存率低有关

IF 5 2区医学

Translational Oncology Pub Date : 2024-10-15 DOI: 10.1016/j.tranon.2024.102153

{"title":"High circulating activin A plasma levels are associated with tumour stage and poor survival in treatment-naive lung squamous cell cancer patients","authors":"","doi":"10.1016/j.tranon.2024.102153","DOIUrl":"10.1016/j.tranon.2024.102153","url":null,"abstract":"<div><h3>Objectives</h3><div>Lung squamous cell carcinoma (LUSC) is associated with a poor prognosis and a lack of specific treatment options. The dysregulation of activin A (ActA) has been reported in various malignancies. Herein, we investigated the diagnostic and prognostic significance of ActA in LUSC.</div></div><div><h3>Materials and methods</h3><div>ActA concentrations were measured using ELISA in plasma samples of 128 LUSC patients (stage I-IV) and 73 controls, and correlated those values with clinicopathological parameters and survival.</div></div><div><h3>Results</h3><div>ActA plasma levels were significantly higher in therapy-naive LUSC patients compared to controls (444.1 <span><math><mo>±</mo></math></span> 310.9 pg/mL vs 338.9 <span><math><mo>±</mo></math></span> 145.5 pg/mL, <em>p</em> = 0.010). ActA levels significantly correlated with advanced stage as well as with T and N factors. High circulating ActA levels were significantly increased in metastatic disease patients compared to M0 disease. Further, patients with ActA levels above a computationally established optimal cut-off value of 443.0 pg/mL had a significantly worse median overall (OS, 17.63 vs 64.77 months, HR 0.391, 95 % CI 0.200–0.762, <em>p</em> < 0.001) and median disease-/progression-free survival (DFS/PFS; 11.57 vs 30.20 months, HR 0.502, 95 % CI 0.248–1.019, <em>p</em> = 0.020). Multivariate analysis revealed that high ActA levels were an independent prognostic factor for shorter OS (<em>p</em> = 0.001) and DFS/PFS (<em>p</em> = 0.018). A newly developed score combining CRP and ActA levels was also an independent prognostic factor for OS and DFS/PFS.</div></div><div><h3>Conclusion</h3><div>Measurement of circulating ActA levels may help identify advanced-stage LUSC patients, and this value could serve as a prognostic parameter in LUSC. Thus, ActA may be a novel blood-based biomarker for identifying LUSC patients with distant metastasis.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433328","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

Proteomic and metabolomic profiles of plasma-derived Extracellular Vesicles differentiate melanoma patients from healthy controls 血浆源性细胞外囊泡的蛋白质组和代谢组特征将黑色素瘤患者与健康对照组区分开来

IF 5 2区医学

Translational Oncology Pub Date : 2024-10-13 DOI: 10.1016/j.tranon.2024.102152

{"title":"Proteomic and metabolomic profiles of plasma-derived Extracellular Vesicles differentiate melanoma patients from healthy controls","authors":"","doi":"10.1016/j.tranon.2024.102152","DOIUrl":"10.1016/j.tranon.2024.102152","url":null,"abstract":"<div><h3>Background</h3><div>Plasma-derived Extracellular Vesicles (EVs) have been suggested as novel biomarkers in melanoma, due to their ability to reflect the cell of origin and ease of collection. This study aimed to identify novel EV biomarkers that can discriminate between disease stages. This was achieved by characterising the plasma-derived EVs of patients with melanoma, and comparing their proteomic and metabolomic profile to those from healthy controls.</div></div><div><h3>Methods</h3><div>EVs were isolated from the plasma of 36 patients with melanoma and 13 healthy controls using Size Exclusion Chromatography. Proteomic and Metabolomic Analyses were performed, and machine learning algorithms were used to identify potential proteins and metabolites to differentiate the plasma-derived EVs from melanoma patients of different disease stages.</div></div><div><h3>Results</h3><div>The concentration and size of the EV population isolated was similar between groups. Proteins (APOC4, PRG4, PLG, TNC, VWF and SERPIND1) and metabolites (lyso PC a C18:2, PC ae C44:3) previously associated with melanoma pathogenesis were identified as relevant in differentiating between disease stages.</div></div><div><h3>Conclusion</h3><div>The results further support the continued investigation of circulating plasma-derived EVs as biomarkers in melanoma. Furthermore, the potential of combined proteo-metabolomic signatures for differentiation between disease stages may provide valuable insights into early detection, prognosis, and personalised treatment strategies.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142422507","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

Role of glucose metabolic reprogramming in colorectal cancer progression and drug resistance 葡萄糖代谢重编程在结直肠癌进展和耐药性中的作用

IF 5 2区医学

Translational Oncology Pub Date : 2024-10-13 DOI: 10.1016/j.tranon.2024.102156

引用次数: 0

First in human intraarterial delivery of tislelizumab for the treatment of pMMR locally advanced rectal cancer: A single-arm, open label, phase II clinical trial 首次在人体动脉内给药 tislelizumab 治疗 pMMR 局部晚期直肠癌：单臂、开放标签 II 期临床试验

IF 5 2区医学

Translational Oncology Pub Date : 2024-10-13 DOI: 10.1016/j.tranon.2024.102154

{"title":"First in human intraarterial delivery of tislelizumab for the treatment of pMMR locally advanced rectal cancer: A single-arm, open label, phase II clinical trial","authors":"","doi":"10.1016/j.tranon.2024.102154","DOIUrl":"10.1016/j.tranon.2024.102154","url":null,"abstract":"<div><h3>Background</h3><div>Intravenous immune checkpoint inhibitors (ICIs) have shown efficacy in treating locally advanced rectal cancer (LARC), but concerns about systemic toxicity persist. This study developed a unique approach termed chemo-immuno-embolization with transcatheter rectal arterial intervention (CIETAI), aiming to enhance the anti-tumor response while minimizing systemic toxicity.</div></div><div><h3>Method</h3><div>This is a prospective, single-arm, phase II clinical trial conducted in Daping hospital. Patients with previously untreated stage II/III LARC underwent preoperative CIETAI combined with PD-1 inhibitor tislelizumab plus oxaliplatin, followed by standard concomitant chemoradiotherapy (capecitabine and 50.4 Gy radiation). Intravenous tislelizumab was administered for an additional two cycles.</div></div><div><h3>Results</h3><div>Between January 2023 and December 2023, a total of 38 patients were enrolled. As the primary endpoint, 17 (44.74 %) patients achieved pathological complete response (TRG0), with a major pathologic response (MPR) rate of 65.79 %. The anal preservation rate was 84.21 % (32/38), and importantly, 15 of 21 patients with low rectal cancer achieved organ preservation with functional maintenance. Eight patients experienced grade 3–4 adverse events (AEs). All immune-related AEs were grade 1–2, with the most common being endocrine toxicity (5/6, 83.33 %). No grade 5 AEs occurred.</div></div><div><h3>Conclusion</h3><div>This study provides preliminary evidence supporting the safety and efficacy of intraarterial tislelizumab delivery in the neoadjuvant setting for LARC. These promising results encourage further exploration in larger cohorts to validate the clinical impact of this novel CIETAI strategy.</div></div><div><h3>Trial registration</h3><div>ClinicalTrials.gov Identifier: NCT05957016.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142422516","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

CAV1 inhibits Xc- system through IFNGR1 to promote ferroptosis to inhibit stemness and improves anti-PD-1 efficacy in breast cancer CAV1 通过 IFNGR1 抑制 Xc- 系统，促进铁凋亡，从而抑制干细胞，提高乳腺癌的抗 PD-1 疗效

IF 5 2区医学

Translational Oncology Pub Date : 2024-10-11 DOI: 10.1016/j.tranon.2024.102149

{"title":"CAV1 inhibits Xc- system through IFNGR1 to promote ferroptosis to inhibit stemness and improves anti-PD-1 efficacy in breast cancer","authors":"","doi":"10.1016/j.tranon.2024.102149","DOIUrl":"10.1016/j.tranon.2024.102149","url":null,"abstract":"<div><div>Breast cancer is the most prevalent malignancy among women worldwide, with breast cancer stem cells (BCSCs) being the primary drivers of metastasis and recurrence. Numerous studies have elucidated the relationship between ferroptosis and cellular stemness, identifying the Xc<sup>-</sup> system as a key regulatory mechanism governing ferroptosis. However, the interplay between CAV1 and ferroptosis, along with its implications for stemness in breast cancer, remains inadequately understood. This gap in knowledge impedes advancements in targeted therapies for breast cancer. We employed immunohistochemistry and bioinformatics analyses to demonstrate the downregulation of CAV1 in breast cancer tissues. Additionally, we utilized CCK-8 assays, EDU staining, and Transwell assays to assess cell proliferation, migration, and invasion capabilities. Furthermore, we evaluated indicators associated with ferroptosis while examining markers related to stemness through sphere culture experiments and flow cytometry techniques. Our findings indicate that CAV1 expression can induce cell death via ferroptosis while simultaneously inhibiting both cell proliferation and features of stemness by upregulating IFNGR1 and promoting ferroptosis. Moreover, our <em>in vivo</em> experiments revealed that overexpression of CAV1 enhances the efficacy of anti-PD-1 therapy. In conclusion, our study elucidates the regulatory role of CAV1 on ferroptosis within breast cancer contexts; it suppresses BCSC characteristics while positioning CAV1 as a promising therapeutic target for combating this disease.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142422444","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

lncRNA WAC-AS1 promotes the progression of gastric cancer through miR-204-5p/HOXC8 axis lncRNA WAC-AS1通过miR-204-5p/HOXC8轴促进胃癌进展

IF 5 2区医学

Translational Oncology Pub Date : 2024-10-11 DOI: 10.1016/j.tranon.2024.102139

引用次数: 0

HSP90AA1 is an unfavorable prognostic factor for hepatocellular carcinoma and contributes to tumorigenesis and chemotherapy resistance HSP90AA1 是肝细胞癌的一个不利预后因素，并导致肿瘤发生和化疗耐药。

IF 5 2区医学

Translational Oncology Pub Date : 2024-10-10 DOI: 10.1016/j.tranon.2024.102148

{"title":"HSP90AA1 is an unfavorable prognostic factor for hepatocellular carcinoma and contributes to tumorigenesis and chemotherapy resistance","authors":"","doi":"10.1016/j.tranon.2024.102148","DOIUrl":"10.1016/j.tranon.2024.102148","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is still one of the leading causes of tumor-related deaths. Accumulating evidence indicates that immunogenic cell death (ICD) could occur in tumor cells. However, ICD-related studies are limited in HCC. This study collected HCC RNA sequencing data from the Cancer Genome Atlas, International Cancer Genome Consortium, and Gene Expression Omnibus databases. R software was used to analyze the expression of ICD in HCC and to screen essential genes with prognostic value. qRT-PCR and WB determined the mRNA and protein expressions of hub gene. Cell viability assay, Clonal formation assay, and Live/dead staining assay were employed to determine the gene functions. After cross-analysis of differentially expressed genes (DEGs) and ICD-related genes (ICDRGs), 7 differentially expressed ICDRGs were identified in HCC. Of them, HSP90AA1, with the most excellent prognostic value in HCC, was selected, whose expression was also validated in public cohorts, cell lines, and clinical tissue samples. High HSP90AA1 expression indicated an inferior prognosis of HCC, and HSP90AA1 knockdown significantly suppressed cell viability and chemotherapy resistance of HCC. ICD-related gene HSP90AA1 was an unfavorable factor for HCC, and high HSP90AA1 expression contributed to tumor cell survival and chemotherapy resistance.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401421","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

Oncolytic vaccinia virus armed with 4–1BBL elicits potent and safe antitumor immunity and enhances the therapeutic efficiency of PD-1/PD-L1 blockade in a pancreatic cancer model 在胰腺癌模型中，以4-1BBL为载体的肿瘤溶解性疫苗病毒可激发强效、安全的抗肿瘤免疫，并提高PD-1/PD-L1阻断的治疗效率。

IF 5 2区医学

Translational Oncology Pub Date : 2024-10-09 DOI: 10.1016/j.tranon.2024.102151

{"title":"Oncolytic vaccinia virus armed with 4–1BBL elicits potent and safe antitumor immunity and enhances the therapeutic efficiency of PD-1/PD-L1 blockade in a pancreatic cancer model","authors":"","doi":"10.1016/j.tranon.2024.102151","DOIUrl":"10.1016/j.tranon.2024.102151","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease with a poor prognosis. Mono-immunotherapy, such as blockade of the PD-1/PD-L1 pathway, for PDAC has proven to be less effective. The systemic exertion of 4–1BB signaling enhanced antitumor immunity accompanied by hepatotoxicity, which is an obstacle for its clinical application. Our study exploits an oncolytic virus armed with 4–1BBL (VV-ΔTK-4L) to locally express 4–1BBL in the tumor microenvironment (TME), thus avoiding hepatotoxicity. VV-ΔTK-4L prolonged the survival time of a pancreatic tumor mouse model and modified the immune status of the TME and spleen. In the TME, the quantities of CD45<sup>+</sup> cells, NK1.1<sup>+</sup> cells, CD11c<sup>+</sup> DCs, CD3<sup>+</sup> <em>T</em>, CD4<sup>+</sup> <em>T</em>, and CD8<sup>+</sup> <em>T</em> cells increased. Compared to VV-ΔTK treatment, VV-ΔTK-4L further increases the number of CD8<sup>+</sup> <em>T</em> cells with effector phenotypes, and downregulates exhaustion-related molecules on CD8<sup>+</sup> <em>T</em> cells, and does not increase the proportion of Foxp3<sup>+</sup> <em>T</em> cells. Thus, the TME of pancreatic cancer was converted from “cold” to “hot” by VV-ΔTK-4L. Blockade of the PD-1/PD-L1 pathway combined with VV-ΔTK-4L further significantly improves the survival ratio of a tumor-bearing mouse model. This study provides a systemic therapeutic strategy and approach for PDAC immunotherapy.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401422","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

MicroRNA-450b-5p modulated RPLP0 promotes hepatocellular carcinoma progression via activating JAK/STAT3 pathway 微RNA-450b-5p调节的RPLP0通过激活JAK/STAT3通路促进肝细胞癌的进展。

IF 5 2区医学

Translational Oncology Pub Date : 2024-10-08 DOI: 10.1016/j.tranon.2024.102150

{"title":"MicroRNA-450b-5p modulated RPLP0 promotes hepatocellular carcinoma progression via activating JAK/STAT3 pathway","authors":"","doi":"10.1016/j.tranon.2024.102150","DOIUrl":"10.1016/j.tranon.2024.102150","url":null,"abstract":"<div><div>Hepatocellular carcinoma (HCC) is distinguished by its insidious onset, difficult treatment, and poor prognosis. Ribosomal Protein Lateral Stalk Subunit P0 (RPLP0) is implicated in numerous tumor progression processes. Nevertheless, the regulatory mechanism of RPLP0 in HCC progression remains unclear. Our study suggested that RPLP0 exhibits high expression levels in HCC and possesses promising diagnostic capabilities, as indicated by its area under the curve (AUC) of 0.908. Further analysis showed that RPLP0 was a significant independent prognostic factor, and elevated expression levels of RPLP0 were linked with poorer overall survival (OS) and progression-free interval (PFI) outcomes. Additionally, reducing RPLP0 levels led to a decrease in HCC cell proliferation, clonality, invasion, migration, and xenograft tumor growth, as well as an increase in apoptosis. Furthermore, our findings indicated that microRNA(miR)-450b-5p induced downregulation of RPLP0, leading to the suppression of the JAK/STAT3 pathway and consequently hindering the advancement of HCC. The study indicates that RPLP0 plays a role as a carcinogenic factor in HCC and carries important diagnostic and prognostic implications. Targeting the miR-450b-5p/RPLP0/JAK/STAT3 axis has potential clinical value in treating HCC.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":null,"pages":null},"PeriodicalIF":5.0,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142393549","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