Translational Oncology最新文献_第3页

Corrigendum to “PMAIP1-Mediated Glucose Metabolism and its Impact on the Tumor Microenvironment in Breast Cancer: Integration of Multi-Omics Analysis and Experimental Validation” [Translational Oncology 52C (2024) 102267]

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-03-01 DOI: 10.1016/j.tranon.2025.102285

Yidong Zhang , Hang Xu , Xuedan Han , Qiyi Yu , Hua Xiao , Lufeng Zheng

引用次数: 0

SPRY1 regulates macrophage M1 polarization in skin aging and melanoma prognosis

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-02-28 DOI: 10.1016/j.tranon.2025.102331

Rongxin Zhao , Xun Zhang , Yingnan Geng , Dan Lu , Yuqing Wang , Han Xie , Xiaofei Zhang , Shunming Xu , Yanyun Cao

Introduction

Skin aging is a complex, multifactorial process involving cellular damage, inflammation, and increased susceptibility to diseases. Despite its importance, the role of SPRY1 in skin aging remains poorly understood. This study aims to investigate the function of SPRY1 in skin aging, particularly its impact on macrophage M1 polarization, and explore its potential as a therapeutic target for mitigating skin aging and melanoma.

Methods

Bioinformatics analyses were performed using datasets from the GTEx and GEO databases, alongside in vitro cellular experiments. These included Weighted Gene Co-expression Network Analysis (WGCNA), single-cell sequencing, and various cellular assays in RAW264.7 murine monocyte/macrophage leukemia cells and NIH/3T3 mouse skin fibroblasts. The assays comprised gene transfection, Cell Counting Kit-8 (CCK-8) assays, quantitative real-time PCR (qRT-PCR), and measurements of reactive oxygen species (ROS) and superoxide dismutase (SOD) activity.

Results

SPRY1 was identified as a key gene within modules linked to skin aging. Single-cell sequencing revealed its enrichment in macrophages and keratinocytes. Knockdown of SPRY1 in RAW264.7 cells resulted in a shift from M1 to M2 macrophage polarization, reduced oxidative stress, and decreased expression of inflammatory markers. In NIH/3T3 cells, SPRY1 knockdown reduced cell viability and lowered the expression of inflammatory genes. Additionally, SPRY1 expression was downregulated in melanoma, and its reduced levels were associated with poorer survival outcomes.

Conclusions

SPRY1 accelerates skin aging by promoting macrophage M1 polarization and may serve as a promising therapeutic target. Future research should focus on in vivo validation and further exploration of its regulatory networks to develop novel treatments.

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引用次数: 0

Radiation from frequent whole-body CT scans induces systemic immunosuppression and immune activation of tumor tissue

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-02-26 DOI: 10.1016/j.tranon.2025.102326

Jigang Dong , Chengrui Fu , Minghao Li , Zhongtang Wang , Baosheng Li

Objective

This study aims to elucidate the impact of repeated whole-body computed tomography (CT) scans on systemic immunity, the tumor immune microenvironment, and tumor control. This inquiry was prompted by clinical observations indicating a decrease in the levels of IFN-β and IFN-γ in patients' blood following whole-body CT scans.

Methods

A Lewis lung carcinoma (LLC) mouse model was established and divided into two groups: a control group and a group subjected to multiple whole-body CT scanning radiation (WBCTSs). The study monitored tumor growth trends across both groups and employed a comprehensive set of analytical techniques—including enzyme-linked immunosorbent assay (ELISA), flow cytometry analysis, immunohistochemistry, RNA sequencing, and single-cell sequencing—to assess differences in cytokine profiles (IFN-β and IFN-γ), proportions of key immune cells, and gene expression variations between the groups.

Results

Repeated CT scan radiation does not promote tumor progression. In tumor tissues subjected to multiple CT scans, an increase in the proportion of CD8+ T cells, elevated interferon levels, and up-regulation of genes associated with killing in CD8+ T cells and genes associated with Ifnb in macrophages were observed. In contrast, radiation from multiple whole-body CT scans resulted in a decrease in the proportion of CD8+ T cells in the blood and spleen, a decrease in serum interferon levels, and down-regulation of killing-related genes in CD8+ T cells.

Conclusion

Our results suggest that repeated whole-body CT scanning radiation induces systemic immunosuppression and immune activation in tumor tissues. Multiple repeated CT scans do not promote tumor progression.

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引用次数: 0

Discovering the Potential Role of the C2 DUSP2+ MCs Subgroup in Lung Adenocarcinoma

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-02-26 DOI: 10.1016/j.tranon.2025.102295

Shengyi Zhang , Xinhan Li , Zhikai Xiahou , Ailing Chen , Renfang Sun , Chao Liu , Jie Yuan

Objective

In both industrialized and developing nations worldwide, lung adenocarcinoma is one of the deadliest malignant tumors and the primary cause of cancer-related deaths. Its cellular heterogeneity is unclear to the fullest extent, although in recent years, its prevalence in younger individuals has increased. Therefore, it is urgent to deepen the understanding of lung adenocarcinoma and explore new therapeutic methods.

Methods

CytoTRACE, Monocle, SCENIC, and enrichment analysis were used to analyze the single cell RNA data, we characterized the biological characteristics of mast cells (MCs) in lung adenocarcinoma patient samples. CellChat was used to analyze and validate the interaction between MCs and tumor cells in lung adenocarcinoma. Prognostic models were used to evaluate and predict the development trend and outcome of a patient's disease, such as the survival time of cancer patients. The python package SCENIC was used to evaluate the enrichment of transcription factors and the activity of regulators in lung adenocarcinoma cell subgroups. CCK-8 assay could validate the activity of a specific cell subgroup sequenced in single cell sequencing to confirm the role of this cell subgroup in tumor proliferation.

Results

Our analysis identified seven major cell types, further grouping MCs within them and identifying four distinct subgroups, including MCs with high DUSP2 expression, which showed some tumor-related characteristics. In addition, we identified the key signaling receptor EGFR and validated it through in vitro knockdown experiments, demonstrating its role in promoting cancer. In addition, we established an independent prognostic indicator, the DUSP2+ MCs risk score, which showed an association between groups with high risk scores and poor outcomes.

Conclusion

These findings shed light on the complex interactions in the lung adenocarcinoma tumor microenvironment and suggest that targeting specific MCs subgroups, particularly through the EGFR signaling pathway, may provide new therapeutic strategies.

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引用次数: 0

MIAT: A pivotal oncogenic long noncoding RNA tunning the hallmarks of solid malignancies

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-02-26 DOI: 10.1016/j.tranon.2025.102329

Monica M. Rostom , Alaa A. Rashwan , Christina D. Sotiropoulou , Sama Z. Hozayen , Abdelhamid M. Abdelhamid , Miriam Mokhtar Abdelhalim , Omar Eltahtawy , Hadir M. Emara , Noha M. Elemam , Christos K. Kontos , Rana A. Youness

Long non-coding RNAs (LncRNAs) have emerged as intriguing players in cellular regulation, challenging the traditional view of non-coding RNAs as mere "dark genome". Non-coding DNA makes up most of the human genome and plays a pivotal role in cancer development. These RNA molecules, which do not code for proteins, have captivated researchers with their diverse and crucial roles in gene regulation, chromatin dynamics, and other cellular processes. In several physiological and pathological circumstances, lncRNAs serve critical functions. This review will tackle the complex function of the lncRNA myocardial infarction-associated transcript (MIAT) in various solid malignancies. A special emphasis would be directed on the correlation between cancer patients' clinicopathological features and the expression profile of MIAT. MIAT is a oncogenic regulator in many malignant tumors, where it can control the growth, invasion, metastasis, and resistance to death of cells. As a result, MIAT is thought to be a possible biomarker and therapeutic target for cancer patients. The biological functions, mechanisms and potential clinical implications of MIAT during carcinogenesis and finally the current possible therapeutic approaches targeting MIAT are also outlined in this review.

{"title":"MIAT: A pivotal oncogenic long noncoding RNA tunning the hallmarks of solid malignancies","authors":"Monica M. Rostom , Alaa A. Rashwan , Christina D. Sotiropoulou , Sama Z. Hozayen , Abdelhamid M. Abdelhamid , Miriam Mokhtar Abdelhalim , Omar Eltahtawy , Hadir M. Emara , Noha M. Elemam , Christos K. Kontos , Rana A. Youness","doi":"10.1016/j.tranon.2025.102329","DOIUrl":"10.1016/j.tranon.2025.102329","url":null,"abstract":"<div><div>Long non-coding RNAs (LncRNAs) have emerged as intriguing players in cellular regulation, challenging the traditional view of non-coding RNAs as mere \"dark genome\". Non-coding DNA makes up most of the human genome and plays a pivotal role in cancer development. These RNA molecules, which do not code for proteins, have captivated researchers with their diverse and crucial roles in gene regulation, chromatin dynamics, and other cellular processes. In several physiological and pathological circumstances, lncRNAs serve critical functions. This review will tackle the complex function of the lncRNA myocardial infarction-associated transcript (MIAT) in various solid malignancies. A special emphasis would be directed on the correlation between cancer patients' clinicopathological features and the expression profile of MIAT. MIAT is a oncogenic regulator in many malignant tumors, where it can control the growth, invasion, metastasis, and resistance to death of cells. As a result, MIAT is thought to be a possible biomarker and therapeutic target for cancer patients. The biological functions, mechanisms and potential clinical implications of MIAT during carcinogenesis and finally the current possible therapeutic approaches targeting MIAT are also outlined in this review.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102329"},"PeriodicalIF":5.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508251","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

Identification of the specific characteristics of neuroendocrine prostate cancer: Immune status, hub genes and treatment

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-02-24 DOI: 10.1016/j.tranon.2025.102320

Jianqing Wang , Yu Wang , Huihui Zhou , Guopeng Yu , Huan Xu , Dajun Gao , Minglun Li , Yuzhuo Wang , Bin Xu

Castration-resistant prostate cancer (CRPC) marks the advanced phase of prostate malignancy, manifested through two principal subtypes: castration-resistant adenocarcinoma (CRPC-adeno) and neuroendocrine prostate cancer (NEPC). This study aims to identify unique central regulatory genes, assess the immunological landscape, and explore potential therapeutic strategies specifically tailored to NEPC. We discovered 1444 differentially expressed genes (DEGs) distinguishing between the two cancer types and identified 12 critical hub genes. Notably, CHST1, MPPED2, and RIPPLY3 emerged as closely associated with the immune cell infiltration pattern, establishing them as top candidates. Prognostic analysis highlighted the potential critical roles of CHST1 and MPPED2 in prostate cancer development, findings corroborated through in vitro and in vivo assays. Moreover, we validated the functions and expression levels of CHST1, MPPED2, and RIPPLY3 in NEPC using cell lines, animal models and human tissues. In the final step, we found that imatinib might be the drug specific to NEPC, which was further confirmed by in vitro cell assay. Our results revealed the clinical characteristics, molecular features, immune cell infiltration pattern in CRPC-adeno and NEPC, and identified and confirmed CHST1, MPPED2, and RIPPLY3 as the critical genes in the development in prostate cancer and NEPC. We also predicted and validated imatinib as the potential specific drugs to NEPC.

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引用次数: 0

Mucin 4 expression is associated with metastasis in triple-negative breast cancer and can be tackled by soluble TNF blockade, improving immunotherapy outcome

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-02-22 DOI: 10.1016/j.tranon.2025.102325

Florencia Mauro , Sofia Bruni , Agustina Dupont , Aldana Schey , Agustina Badalini , Gloria Inurrigarro , Silvina Figurelli , Sabrina Barchuk , Daniel Lopez Della Vecchia , Ernesto Gil Deza , Yanina Rivenson , Agustin Nava , Elmer Fernandez , Alejandro Urtreger , Rosalia Cordo Russo , María Florencia Mercogliano , Roxana Schillaci

Purpose

Triple-negative breast cancer (TNBC) has the worst prognosis among breast cancers. Immunotherapy is a therapeutic option, but there is no biomarker to guide promising combination treatments. Mucin 4 (MUC4) favors metastasis in preclinical cancer models. This study evaluates the efficacy of soluble TNF (sTNF) neutralization to tackle MUC4 expression preventing metastasis in combination with immunotherapy, and the potential use of MUC4 as a prognostic and predictive biomarker in TNBC patients.

Experimental Design

To explore TNF modulation of MUC4 expression, a panel of TNBC cell lines was used. To assess the effect of sTNF blockade with a dominant negative molecule in combination with anti-PD-1 antibody on lung metastasis and overall survival (OS), 4T1 and LMM3 tumors were used. MUC4, PD-L1 and Ki-67 expression was evaluated by immunohistochemistry, and tumor infiltrating lymphocytes (TILs) were assessed by H&E staining, in a cohort of 49 early TNBC patients treated with chemotherapy.

Results

TNF neutralization reduces MUC4 expression in TNBC cell lines. Only the combination of sTNF blockade with anti-PD-1 antibody prevents metastasis and increases mice survival. In early TNBC patients MUC4 expression is inversely associated with TILs presence and PD-L1 and Ki-67 expression. Finally, MUC4 is associated with metastasis and is an independent biomarker of poor OS.

Conclusions

We proved the existence of a sTNF/MUC4 axis in TNBC that can be actionable by sTNF neutralization, preventing metastasis. We suggest that MUC4 is a suitable biomarker to guide immunotherapy in TNBC, together with the administration of sTNF blocking drugs to improve outcome.

{"title":"Mucin 4 expression is associated with metastasis in triple-negative breast cancer and can be tackled by soluble TNF blockade, improving immunotherapy outcome","authors":"Florencia Mauro , Sofia Bruni , Agustina Dupont , Aldana Schey , Agustina Badalini , Gloria Inurrigarro , Silvina Figurelli , Sabrina Barchuk , Daniel Lopez Della Vecchia , Ernesto Gil Deza , Yanina Rivenson , Agustin Nava , Elmer Fernandez , Alejandro Urtreger , Rosalia Cordo Russo , María Florencia Mercogliano , Roxana Schillaci","doi":"10.1016/j.tranon.2025.102325","DOIUrl":"10.1016/j.tranon.2025.102325","url":null,"abstract":"<div><h3>Purpose</h3><div>Triple-negative breast cancer (TNBC) has the worst prognosis among breast cancers. Immunotherapy is a therapeutic option, but there is no biomarker to guide promising combination treatments. Mucin 4 (MUC4) favors metastasis in preclinical cancer models. This study evaluates the efficacy of soluble TNF (sTNF) neutralization to tackle MUC4 expression preventing metastasis in combination with immunotherapy, and the potential use of MUC4 as a prognostic and predictive biomarker in TNBC patients.</div></div><div><h3>Experimental Design</h3><div>To explore TNF modulation of MUC4 expression, a panel of TNBC cell lines was used. To assess the effect of sTNF blockade with a dominant negative molecule in combination with anti-PD-1 antibody on lung metastasis and overall survival (OS), 4T1 and LMM3 tumors were used. MUC4, PD-L1 and Ki-67 expression was evaluated by immunohistochemistry, and tumor infiltrating lymphocytes (TILs) were assessed by H&E staining, in a cohort of 49 early TNBC patients treated with chemotherapy.</div></div><div><h3>Results</h3><div>TNF neutralization reduces MUC4 expression in TNBC cell lines. Only the combination of sTNF blockade with anti-PD-1 antibody prevents metastasis and increases mice survival. In early TNBC patients MUC4 expression is inversely associated with TILs presence and PD-L1 and Ki-67 expression. Finally, MUC4 is associated with metastasis and is an independent biomarker of poor OS.</div></div><div><h3>Conclusions</h3><div>We proved the existence of a sTNF/MUC4 axis in TNBC that can be actionable by sTNF neutralization, preventing metastasis. We suggest that MUC4 is a suitable biomarker to guide immunotherapy in TNBC, together with the administration of sTNF blocking drugs to improve outcome.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102325"},"PeriodicalIF":5.0,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463524","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

RNF135 promotes the stemness of breast cancer cells by ubiquitinating and degrading DDX58

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-02-21 DOI: 10.1016/j.tranon.2025.102321

Anqi Hu , Lin Zhang , Lei Cao , Haifeng Li , Riqing Huang , Xiaohong Zhou , Yanxia Shi , Baojiang Li

Background

RING finger protein 135 (RNF135) is identified as a regulator in certain cancer types. However, its role and molecular mechanisms in breast cancer are still unclear.

Methods

Herein, we investigated the level of RNF135 in tumor tissues of breast patients using the online database and confirmed the data by real-time PCR and western blot analysis. The effects of RNF135 on stemness maintenance and migration/invasion capability of breast cells were investigated by sphere formation, flow cytometry, and transwell assays. Limiting dilution xenograft assay and metastatic model were applied to assess the implications of RNF135 in tumorigenesis, chemoresistance, and metastasis.

Results

Our results revealed that RNF135 was upregulated in tumor tissues of breast patients, especially in metastatic patients. Knockdown of RNF135 suppressed stemness, and migration/invasion capability of breast cancer cells. Conversely, RNF135 overexpression enhanced the stemness and migration/invasion ability of breast cancer cells. Limiting dilution xenograft and metastatic assays demonstrated that RNF135 was required for the self-renewal of CSCs to initiate breast cancer development and metastasis. Mechanistically, DDX58 was identified as the substrate of RNF135 and RNF135 could facilitated the ubiquitination and degradation of DDX58. Notably, overexpression of DDX58 rescued the promoting effects of RNF135 on the stemness and migration/invasion ability of breast cancer cells.

Conclusions

Overall, our results implied that RNF135 promotes the stemness of breast cancer cells by ubiquitinating and degrading DDX58 and targeting of RNF135/DDX58 axis might be a feasible method to suppress tumorigenesis and metastasis of breast cancer patients.

{"title":"RNF135 promotes the stemness of breast cancer cells by ubiquitinating and degrading DDX58","authors":"Anqi Hu , Lin Zhang , Lei Cao , Haifeng Li , Riqing Huang , Xiaohong Zhou , Yanxia Shi , Baojiang Li","doi":"10.1016/j.tranon.2025.102321","DOIUrl":"10.1016/j.tranon.2025.102321","url":null,"abstract":"<div><h3>Background</h3><div>RING finger protein 135 (RNF135) is identified as a regulator in certain cancer types. However, its role and molecular mechanisms in breast cancer are still unclear.</div></div><div><h3>Methods</h3><div>Herein, we investigated the level of RNF135 in tumor tissues of breast patients using the online database and confirmed the data by real-time PCR and western blot analysis. The effects of RNF135 on stemness maintenance and migration/invasion capability of breast cells were investigated by sphere formation, flow cytometry, and transwell assays. Limiting dilution xenograft assay and metastatic model were applied to assess the implications of RNF135 in tumorigenesis, chemoresistance, and metastasis.</div></div><div><h3>Results</h3><div>Our results revealed that RNF135 was upregulated in tumor tissues of breast patients, especially in metastatic patients. Knockdown of RNF135 suppressed stemness, and migration/invasion capability of breast cancer cells. Conversely, RNF135 overexpression enhanced the stemness and migration/invasion ability of breast cancer cells. Limiting dilution xenograft and metastatic assays demonstrated that RNF135 was required for the self-renewal of CSCs to initiate breast cancer development and metastasis. Mechanistically, DDX58 was identified as the substrate of RNF135 and RNF135 could facilitated the ubiquitination and degradation of DDX58. Notably, overexpression of DDX58 rescued the promoting effects of RNF135 on the stemness and migration/invasion ability of breast cancer cells.</div></div><div><h3>Conclusions</h3><div>Overall, our results implied that RNF135 promotes the stemness of breast cancer cells by ubiquitinating and degrading DDX58 and targeting of RNF135/DDX58 axis might be a feasible method to suppress tumorigenesis and metastasis of breast cancer patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102321"},"PeriodicalIF":5.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143453502","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

Individualized tumor-reactive T cells exhibit a potent anti-tumor response in prostate cancer

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-02-21 DOI: 10.1016/j.tranon.2025.102322

Lianjun He , Nanlin Jiao , Xing Bao , Yao Wu , Xueyi Qian , Weijie He , Han Zhen , Lei Tang , Huimin Shao , Dong Zhuo , Houbao Huang , Zhenyu Xu

Background

Cellular immunotherapy exhibits promise in treating blood tumors. However, its application for solid tumors is impeded by their heterogeneity and complex microenvironments. The development of individualized multitarget therapy may be the key to overcoming the challenge of tumor heterogeneity.

Methods

To generate tumor-reactive T cells, we modified the conditional reprogramming primary cell culture method by to establish a primary prostate cancer cell culture approach, refer to as eCR (enhanced conditional reprogramming). Then, Tumor tissue–derived primary cells were physically lysed and loaded into dendric cells, which, in turn, were co-cultured with peripheral blood T cells to induced individualized tumor-reactive T cells.

Results

Our improved culture method could use a small amount of fresh or frozen tumor specimens (including biopsy specimens), which can be amplified in vitro while maintaining their original characteristics, without contamination by heterologous antigens. Furthermore, a series of in vitro and in vivo experiments revealed these tumor-reactive T cells exhibited specific and effective killing of tumor cells through their ability to recognize neoantigens in cancer.

Conclusion

In this study, we developed a protocol for the generation of tumor-responsive T cells based on autologous tumor antigens in patients with prostate cancer. This platform is characterized by its multitargeted, individualized, affordability, and minimal adverse effects, holding significant promise in the treatment of prostate cancer as well as other solid tumors.

{"title":"Individualized tumor-reactive T cells exhibit a potent anti-tumor response in prostate cancer","authors":"Lianjun He , Nanlin Jiao , Xing Bao , Yao Wu , Xueyi Qian , Weijie He , Han Zhen , Lei Tang , Huimin Shao , Dong Zhuo , Houbao Huang , Zhenyu Xu","doi":"10.1016/j.tranon.2025.102322","DOIUrl":"10.1016/j.tranon.2025.102322","url":null,"abstract":"<div><h3>Background</h3><div>Cellular immunotherapy exhibits promise in treating blood tumors. However, its application for solid tumors is impeded by their heterogeneity and complex microenvironments. The development of individualized multitarget therapy may be the key to overcoming the challenge of tumor heterogeneity.</div></div><div><h3>Methods</h3><div>To generate tumor-reactive T cells, we modified the conditional reprogramming primary cell culture method by to establish a primary prostate cancer cell culture approach, refer to as eCR (enhanced conditional reprogramming). Then, Tumor tissue–derived primary cells were physically lysed and loaded into dendric cells, which, in turn, were co-cultured with peripheral blood T cells to induced individualized tumor-reactive T cells.</div></div><div><h3>Results</h3><div>Our improved culture method could use a small amount of fresh or frozen tumor specimens (including biopsy specimens), which can be amplified in vitro while maintaining their original characteristics, without contamination by heterologous antigens. Furthermore, a series of in vitro and in vivo experiments revealed these tumor-reactive T cells exhibited specific and effective killing of tumor cells through their ability to recognize neoantigens in cancer.</div></div><div><h3>Conclusion</h3><div>In this study, we developed a protocol for the generation of tumor-responsive T cells based on autologous tumor antigens in patients with prostate cancer. This platform is characterized by its multitargeted, individualized, affordability, and minimal adverse effects, holding significant promise in the treatment of prostate cancer as well as other solid tumors.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102322"},"PeriodicalIF":5.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463415","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

Thiostrepton suppresses intrahepatic cholangiocarcinoma progression via FOXM1-mediated tumor-associated macrophages reprogramming

IF 5 2区医学 Q2 Medicine

Translational Oncology

Pub Date : 2025-02-21 DOI: 10.1016/j.tranon.2025.102327

Yu Li , Yifan Jiang , Rongliang Tong , Bo Ding , Jiangzhen Ge , Keyi Du , Jingqi Sun , Zheng Tang , Diyu Chen , Jian Wu

Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer with an extremely poor prognosis, highlighting the urgent need for new treatment options. Recent studies increasingly suggest that the Forkhead box M1 (FOXM1) transcription factor may serve as a candidate target for cancer immunotherapy. However, its role and the underlying molecular mechanisms in ICC remain not fully understood. Here, we identify thiostrepton (TST) as a potent FOXM1 inhibitor, capable of exerting “dual anti-tumor” effects in ICC. On one hand, TST effectively suppresses tumor cell proliferation and metastasis. On the other hand, TST treatment improves the tumor immune microenvironment by reprogramming tumor-associated macrophages (TAMs), thereby enhancing anti-tumor immune responses. Mechanistically, TST directly alleviates ICC progression by arresting the cell cycle, promoting apoptosis, and inhibiting the epithelial-mesenchymal transition (EMT) process. Furthermore, TST-treated tumor cells secrete cytokines that drive TAMs repolarization toward the tumor-suppressive M1 phenotype. Overall, our results indicate that FOXM1 can serve as a novel target for ICC immunotherapy. By targeting FOXM1, TST exerts “dual anti-tumor” effects and has the potential to become a promising immunotherapy agent for ICC patients.

{"title":"Thiostrepton suppresses intrahepatic cholangiocarcinoma progression via FOXM1-mediated tumor-associated macrophages reprogramming","authors":"Yu Li , Yifan Jiang , Rongliang Tong , Bo Ding , Jiangzhen Ge , Keyi Du , Jingqi Sun , Zheng Tang , Diyu Chen , Jian Wu","doi":"10.1016/j.tranon.2025.102327","DOIUrl":"10.1016/j.tranon.2025.102327","url":null,"abstract":"<div><div>Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer with an extremely poor prognosis, highlighting the urgent need for new treatment options. Recent studies increasingly suggest that the Forkhead box M1 (FOXM1) transcription factor may serve as a candidate target for cancer immunotherapy. However, its role and the underlying molecular mechanisms in ICC remain not fully understood. Here, we identify thiostrepton (TST) as a potent FOXM1 inhibitor, capable of exerting “dual anti-tumor” effects in ICC. On one hand, TST effectively suppresses tumor cell proliferation and metastasis. On the other hand, TST treatment improves the tumor immune microenvironment by reprogramming tumor-associated macrophages (TAMs), thereby enhancing anti-tumor immune responses. Mechanistically, TST directly alleviates ICC progression by arresting the cell cycle, promoting apoptosis, and inhibiting the epithelial-mesenchymal transition (EMT) process. Furthermore, TST-treated tumor cells secrete cytokines that drive TAMs repolarization toward the tumor-suppressive M1 phenotype. Overall, our results indicate that FOXM1 can serve as a novel target for ICC immunotherapy. By targeting FOXM1, TST exerts “dual anti-tumor” effects and has the potential to become a promising immunotherapy agent for ICC patients.</div></div>","PeriodicalId":48975,"journal":{"name":"Translational Oncology","volume":"54 ","pages":"Article 102327"},"PeriodicalIF":5.0,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463714","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