Triple-negative breast Cancer (TNBC) is an aggressive subtype lacking estrogen, progesterone, and HER2 receptors. Known for limited targeted therapies, it poses challenges and requires personalized treatment strategies. Differential analysis revealed a significant decrease in keratin 81 (KRT81) expression in non-TNBC samples and an increase in TNBC samples, lower KRT81 expression correlated with better TNBC patient outcomes. It emerged as an independent predictive factor for TNBC, with associations found between its expression and clinically relevant features. We further developed a nomogram for survival probability assessment based on Cox regression results, demonstrating its accuracy through calibration curves. Gene annotation analysis indicated that KRT81 is involved in immune-related pathways and tumor cell adhesion. KRT81 is associated with immune cell infiltration of Follicular helper T cells (Tfh) and CD8 + T cells, suggesting its potential impact on the immunological microenvironment. The study delved into KRT81's predictive value for immunotherapy responses, high expression of KRT81 was associated with greater potential for immune evasion. Single-cell RNA sequencing analysis pinpointed KRT81 expression within a specific malignant subtype which was a risk factor for TNBC. Furthermore, KRT81 promoted TNBC cell proliferation, migration, invasion, and adhesion was confirmed by gene knockout or overexpression assay. Co-culture experiments further indicated KRT81's potential role in inhibiting CD8 + T cells, and correlation analysis implied KRT81 was highly correlated with immune checkpoint CD276, providing insights into its involvement in the immune microenvironment via CD276. In conclusion, this comprehensive study positions KRT81 as a promising prognostic marker for predicting tumor progression and immunotherapy responses in TNBC.
{"title":"The prognostic marker KRT81 is involved in suppressing CD8 + T cells and predicts immunotherapy response for triple-negative breast cancer.","authors":"Zhideng Yan, Zhihui Zhong, Chuanke Shi, Muyin Feng, Xiaoqiang Feng, Tong Liu","doi":"10.1080/15384047.2024.2355705","DOIUrl":"10.1080/15384047.2024.2355705","url":null,"abstract":"<p><p>Triple-negative breast Cancer (TNBC) is an aggressive subtype lacking estrogen, progesterone, and HER2 receptors. Known for limited targeted therapies, it poses challenges and requires personalized treatment strategies. Differential analysis revealed a significant decrease in keratin 81 (KRT81) expression in non-TNBC samples and an increase in TNBC samples, lower KRT81 expression correlated with better TNBC patient outcomes. It emerged as an independent predictive factor for TNBC, with associations found between its expression and clinically relevant features. We further developed a nomogram for survival probability assessment based on Cox regression results, demonstrating its accuracy through calibration curves. Gene annotation analysis indicated that KRT81 is involved in immune-related pathways and tumor cell adhesion. KRT81 is associated with immune cell infiltration of Follicular helper T cells (Tfh) and CD8 + T cells, suggesting its potential impact on the immunological microenvironment. The study delved into KRT81's predictive value for immunotherapy responses, high expression of KRT81 was associated with greater potential for immune evasion. Single-cell RNA sequencing analysis pinpointed KRT81 expression within a specific malignant subtype which was a risk factor for TNBC. Furthermore, KRT81 promoted TNBC cell proliferation, migration, invasion, and adhesion was confirmed by gene knockout or overexpression assay. Co-culture experiments further indicated KRT81's potential role in inhibiting CD8 + T cells, and correlation analysis implied KRT81 was highly correlated with immune checkpoint CD276, providing insights into its involvement in the immune microenvironment via CD276. In conclusion, this comprehensive study positions KRT81 as a promising prognostic marker for predicting tumor progression and immunotherapy responses in TNBC.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11123506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-31Epub Date: 2024-07-10DOI: 10.1080/15384047.2024.2376410
Yuhua Qu, Anhui Zeng, Yulu Cheng, Shengchun Li
Substantial advancements have been made in recent years in comprehending immune memory, which enhances the secondary response through prior infections. The ability of vertebrate T and B lymphocytes to exhibit classic recall responses has long been regarded as a distinguishing characteristic. However, natural killer (NK) cells have been found to acquire immunological memory in a manner akin to T and B cells. The fundamental principles derived from the investigation of NK cell memory offer novel insights into innate immunity and have the potential to pave the way for innovative strategies to enhance therapeutic interventions against multiple diseases including cancer. Here, we reviewed the fundamental characteristics, memory development and regulatory mechanism of NK cell memory. Moreover, we will conduct a comprehensive evaluation of the accomplishments, obstacles, and future direction pertaining to the utilization of NK cell memory in the field of cancer immunotherapy.
近年来,人们在理解免疫记忆方面取得了长足进步,免疫记忆可增强对先前感染的次级反应。脊椎动物的 T 淋巴细胞和 B 淋巴细胞能够表现出典型的记忆反应,这一点一直被认为是与众不同的特征。然而,人们发现自然杀伤(NK)细胞获得免疫记忆的方式与 T 和 B 细胞相似。从对 NK 细胞记忆的研究中得出的基本原理提供了对先天性免疫的新见解,并有可能为创新战略铺平道路,以加强对包括癌症在内的多种疾病的治疗干预。在此,我们回顾了 NK 细胞记忆的基本特征、记忆发展和调控机制。此外,我们还将对癌症免疫疗法领域利用 NK 细胞记忆的成就、障碍和未来方向进行全面评估。
{"title":"Natural killer cell memory: challenges and opportunities for cancer immunotherapy.","authors":"Yuhua Qu, Anhui Zeng, Yulu Cheng, Shengchun Li","doi":"10.1080/15384047.2024.2376410","DOIUrl":"10.1080/15384047.2024.2376410","url":null,"abstract":"<p><p>Substantial advancements have been made in recent years in comprehending immune memory, which enhances the secondary response through prior infections. The ability of vertebrate T and B lymphocytes to exhibit classic recall responses has long been regarded as a distinguishing characteristic. However, natural killer (NK) cells have been found to acquire immunological memory in a manner akin to T and B cells. The fundamental principles derived from the investigation of NK cell memory offer novel insights into innate immunity and have the potential to pave the way for innovative strategies to enhance therapeutic interventions against multiple diseases including cancer. Here, we reviewed the fundamental characteristics, memory development and regulatory mechanism of NK cell memory. Moreover, we will conduct a comprehensive evaluation of the accomplishments, obstacles, and future direction pertaining to the utilization of NK cell memory in the field of cancer immunotherapy.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11238922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-31Epub Date: 2024-08-03DOI: 10.1080/15384047.2024.2386753
Dan Xiong, Yafei Xu, Hongbo Wang, Yunlin Ye
Nephroblastoma, an overexpressed gene (NOV) protein, plays an important role in proliferation, differentiation, angiogenesis, adhesion, invasion and tumorigenesis, but the function of amino-truncated NOV is different. This study is to investigate the role of amino-truncated NOV in the progression of bladder cancer. Using immunohistochemistry and Western blot analysis, we detected the amino-truncated NOV in bladder cancer, and statistical analysis was performed to estimate the association between the expression of amino-truncated NOV and the patient's prognosis by SPSS 19.0. With transduction of amino-truncated NOV, we evaluated alteration for proliferation, migration, invasion and chemoresistance in bladder cancer cells, as well as some proteins related to Wnt/β-catenin pathway and epithelial-mesenchymal transition. The truncated variant of the NOV protein was located in a nucleus other than the cytoplasm and highly expressed in bladder cancer, which was also linked to higher pathological grade and positive lymph node metastasis as well as recurrence. The exact sequence of this truncated protein was confirmed, and it was a 26-kDa splicing. The truncated NOV protein found in bladder cancer was cut at the 187th amino acid of the full-length protein. It was also involved in bladder cancer progression and chemoresistance through a mechanism involving epithelial-mesenchymal transition (EMT) and the Wnt/β-catenin signaling pathway. Our findings provide experimental evidence that the nuclear NOV protein expression is a potential biomarker in the prognostic evaluation of bladder cancer and enhanced amino-truncated NOV expression is potentially important for bladder cancer cell invasion, metastasis and chemoresistance during progression.
肾母细胞瘤过表达基因(NOV)蛋白在增殖、分化、血管生成、粘附、侵袭和肿瘤发生中起着重要作用,但氨基截短的NOV的功能有所不同。本研究旨在探讨氨基截短的 NOV 在膀胱癌进展过程中的作用。通过免疫组化和 Western 印迹分析,我们检测了膀胱癌中的氨基截短 NOV,并通过 SPSS 19.0 进行了统计分析,以估计氨基截短 NOV 的表达与患者预后之间的关联。通过转导氨基截短NOV,我们评估了膀胱癌细胞的增殖、迁移、侵袭和化疗耐受性的变化,以及与Wnt/β-catenin通路和上皮-间质转化相关的一些蛋白的变化。NOV蛋白的截短变体位于细胞核而非细胞质中,在膀胱癌中高表达,也与较高的病理分级、阳性淋巴结转移和复发有关。这种截短蛋白的确切序列已得到证实,它是一个 26 kDa 的剪接体。在膀胱癌中发现的截短 NOV 蛋白在全长蛋白的第 187 个氨基酸处被切断。它还通过涉及上皮-间质转化(EMT)和Wnt/β-catenin信号通路的机制参与了膀胱癌的进展和化疗抗性。我们的研究结果提供了实验证据,证明核NOV蛋白表达是膀胱癌预后评估的潜在生物标志物,而氨基截短的NOV表达增强可能对膀胱癌细胞的侵袭、转移和化疗过程中的耐药性有重要影响。
{"title":"Amino-truncated NOV expression and its correlation with clinicopathologic features, prognosis, metastasis, and chemoresistance in bladder cancer.","authors":"Dan Xiong, Yafei Xu, Hongbo Wang, Yunlin Ye","doi":"10.1080/15384047.2024.2386753","DOIUrl":"10.1080/15384047.2024.2386753","url":null,"abstract":"<p><p>Nephroblastoma, an overexpressed gene (NOV) protein, plays an important role in proliferation, differentiation, angiogenesis, adhesion, invasion and tumorigenesis, but the function of amino-truncated NOV is different. This study is to investigate the role of amino-truncated NOV in the progression of bladder cancer. Using immunohistochemistry and Western blot analysis, we detected the amino-truncated NOV in bladder cancer, and statistical analysis was performed to estimate the association between the expression of amino-truncated NOV and the patient's prognosis by SPSS 19.0. With transduction of amino-truncated NOV, we evaluated alteration for proliferation, migration, invasion and chemoresistance in bladder cancer cells, as well as some proteins related to Wnt/β-catenin pathway and epithelial-mesenchymal transition. The truncated variant of the NOV protein was located in a nucleus other than the cytoplasm and highly expressed in bladder cancer, which was also linked to higher pathological grade and positive lymph node metastasis as well as recurrence. The exact sequence of this truncated protein was confirmed, and it was a 26-kDa splicing. The truncated NOV protein found in bladder cancer was cut at the 187th amino acid of the full-length protein. It was also involved in bladder cancer progression and chemoresistance through a mechanism involving epithelial-mesenchymal transition (EMT) and the Wnt/β-catenin signaling pathway. Our findings provide experimental evidence that the nuclear NOV protein expression is a potential biomarker in the prognostic evaluation of bladder cancer and enhanced amino-truncated NOV expression is potentially important for bladder cancer cell invasion, metastasis and chemoresistance during progression.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299625/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141888507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-31Epub Date: 2024-03-06DOI: 10.1080/15384047.2024.2317999
Samatha M Jain, Shruthi Nagainallur Ravichandran, Makalakshmi Murali Kumar, Antara Banerjee, Alexander Sun-Zhang, Hong Zhang, Rupak Pathak, Xiao-Feng Sun, Surajit Pathak
Rectal cancer accounts for the second highest cancer-related mortality, which is predominant in Western civilizations. The treatment for rectal cancers includes surgery, radiotherapy, chemotherapy, and immunotherapy. Radiotherapy, specifically external beam radiation therapy, is the most common way to treat rectal cancer because radiation not only limits cancer progression but also significantly reduces the risk of local recurrence. However, therapeutic radiation-induced radioresistance to rectal cancer cells and toxicity to normal tissues are major drawbacks. Therefore, understanding the mechanistic basis of developing radioresistance during and after radiation therapy would provide crucial insight to improve clinical outcomes of radiation therapy for rectal cancer patients. Studies by various groups have shown that radiotherapy-mediated changes in the tumor microenvironment play a crucial role in developing radioresistance. Therapeutic radiation-induced hypoxia and functional alterations in the stromal cells, specifically tumor-associated macrophage (TAM) and cancer-associated fibroblasts (CAF), play a crucial role in developing radioresistance. In addition, signaling pathways, such as - the PI3K/AKT pathway, Wnt/β-catenin signaling, and the hippo pathway, modulate the radiation responsiveness of cancer cells. Different radiosensitizers, such as small molecules, microRNA, nanomaterials, and natural and chemical sensitizers, are being used to increase the effectiveness of radiotherapy. This review highlights the mechanism responsible for developing radioresistance of rectal cancer following radiotherapy and potential strategies to enhance the effectiveness of radiotherapy for better management of rectal cancer.
{"title":"Understanding the molecular mechanism responsible for developing therapeutic radiation-induced radioresistance of rectal cancer and improving the clinical outcomes of radiotherapy - A review.","authors":"Samatha M Jain, Shruthi Nagainallur Ravichandran, Makalakshmi Murali Kumar, Antara Banerjee, Alexander Sun-Zhang, Hong Zhang, Rupak Pathak, Xiao-Feng Sun, Surajit Pathak","doi":"10.1080/15384047.2024.2317999","DOIUrl":"10.1080/15384047.2024.2317999","url":null,"abstract":"<p><p>Rectal cancer accounts for the second highest cancer-related mortality, which is predominant in Western civilizations. The treatment for rectal cancers includes surgery, radiotherapy, chemotherapy, and immunotherapy. Radiotherapy, specifically external beam radiation therapy, is the most common way to treat rectal cancer because radiation not only limits cancer progression but also significantly reduces the risk of local recurrence. However, therapeutic radiation-induced radioresistance to rectal cancer cells and toxicity to normal tissues are major drawbacks. Therefore, understanding the mechanistic basis of developing radioresistance during and after radiation therapy would provide crucial insight to improve clinical outcomes of radiation therapy for rectal cancer patients. Studies by various groups have shown that radiotherapy-mediated changes in the tumor microenvironment play a crucial role in developing radioresistance. Therapeutic radiation-induced hypoxia and functional alterations in the stromal cells, specifically tumor-associated macrophage (TAM) and cancer-associated fibroblasts (CAF), play a crucial role in developing radioresistance. In addition, signaling pathways, such as - the PI3K/AKT pathway, Wnt/β-catenin signaling, and the hippo pathway, modulate the radiation responsiveness of cancer cells. Different radiosensitizers, such as small molecules, microRNA, nanomaterials, and natural and chemical sensitizers, are being used to increase the effectiveness of radiotherapy. This review highlights the mechanism responsible for developing radioresistance of rectal cancer following radiotherapy and potential strategies to enhance the effectiveness of radiotherapy for better management of rectal cancer.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10936619/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140038777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-31Epub Date: 2024-03-23DOI: 10.1080/15384047.2024.2332000
Hannah M Hicks, Veronica L Nassar, Jane Lund, Madison M Rose, Rebecca E Schweppe
Thyroid cancer is one of the deadliest endocrine cancers, and its incidence has been increasing. While mutations in BRAF are common in thyroid cancer, advanced PTC patients currently lack therapeutic options targeting the MAPK pathway, and despite the approved combination of BRAF and MEK1/2 inhibition for BRAF-mutant ATC, resistance often occurs. Here, we assess growth and signaling responses to combined BRAF and MEK1/2 inhibition in a panel of BRAF-mutant thyroid cancer cell lines. We first showed that combined BRAF and MEK1/2 inhibition synergistically inhibits cell growth in four out of six of the -BRAF-mutant thyroid cancer cell lines tested. Western blotting showed that the MAPK pathway was robustly inhibited in all cell lines. Therefore, to identify potential mechanisms of resistance, we performed RNA-sequencing in cells sensitive or resistant to MEK1/2 inhibition. In response to MEK1/2 inhibition, we identified a downregulation of Aurora Kinase B (AURKB) in sensitive but not resistant cells. We further demonstrated that combined MEK1/2 and AURKB inhibition slowed cell growth, which was phenocopied by inhibiting AURKB and ERK1/2. Finally, we show that combined AURKB and ERK1/2 inhibition induces apoptosis in BRAF-mutant thyroid cancer cell lines, together suggesting a potential combination therapy for BRAF-mutant thyroid cancer patients.
{"title":"The effects of Aurora Kinase inhibition on thyroid cancer growth and sensitivity to MAPK-directed therapies.","authors":"Hannah M Hicks, Veronica L Nassar, Jane Lund, Madison M Rose, Rebecca E Schweppe","doi":"10.1080/15384047.2024.2332000","DOIUrl":"10.1080/15384047.2024.2332000","url":null,"abstract":"<p><p>Thyroid cancer is one of the deadliest endocrine cancers, and its incidence has been increasing. While mutations in <i>BRAF</i> are common in thyroid cancer, advanced PTC patients currently lack therapeutic options targeting the MAPK pathway, and despite the approved combination of BRAF and MEK1/2 inhibition for <i>BRAF-</i>mutant ATC, resistance often occurs. Here, we assess growth and signaling responses to combined BRAF and MEK1/2 inhibition in a panel of <i>BRAF-</i>mutant thyroid cancer cell lines. We first showed that combined BRAF and MEK1/2 inhibition synergistically inhibits cell growth in four out of six of the -<i>BRAF</i>-mutant thyroid cancer cell lines tested. Western blotting showed that the MAPK pathway was robustly inhibited in all cell lines. Therefore, to identify potential mechanisms of resistance, we performed RNA-sequencing in cells sensitive or resistant to MEK1/2 inhibition. In response to MEK1/2 inhibition, we identified a downregulation of Aurora Kinase B (AURKB) in sensitive but not resistant cells. We further demonstrated that combined MEK1/2 and AURKB inhibition slowed cell growth, which was phenocopied by inhibiting AURKB and ERK1/2. Finally, we show that combined AURKB and ERK1/2 inhibition induces apoptosis in <i>BRAF-</i>mutant thyroid cancer cell lines, together suggesting a potential combination therapy for <i>BRAF</i>-mutant thyroid cancer patients.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10962586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140193439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-31Epub Date: 2024-06-11DOI: 10.1080/15384047.2024.2365452
JiaMin Huang, Eva Michaud, Surashri Shinde-Jadhav, Sabina Fehric, Gautier Marcq, Jose Joao Mansure, Fabio Cury, Fadi Brimo, Ciriaco A Piccirillo, Wassim Kassouf
MIBC is a highly lethal disease, and the patient survival rate has not improved significantly over the last decades. UPPL is a cell line that can be used to recapitulate the luminal-like molecular subtype of bladder cancer and to discover effective treatments to be translated in patients. Here, we investigate the effects of combinational treatments of radiotherapy and immunotherapy in this recently characterized UPPL tumor-bearing mice. We first characterized the baseline tumor microenvironment and the effect of radiation, anti-PD-L1, and combinatorial treatments. Then, the mice were re-challenged with a second tumor (rechallenged tumor) in the contralateral flank of the first tumor to assess the immunological memory. Radiation slowed down the tumor growth. All treatments also decreased the neutrophil population and increased the T cell population. Anti-PD-L1 therapy was not able to synergize with radiation to further delay tumor growth. Furthermore, none of the treatments were able to generate immune memory. The treatments were not sufficient to induce a significant and lasting pool of memory cells. We show here that anti-PD-L1 treatment added to radiotherapy was not enough to achieve T cell-mediated memory in UPPL tumors. Stronger T cell activation signals may be required to enhance radiation efficacy in luminal-like bladder cancer.
{"title":"Effects of combined radiotherapy with immune checkpoint blockade on immunological memory in luminal-like subtype murine bladder cancer model.","authors":"JiaMin Huang, Eva Michaud, Surashri Shinde-Jadhav, Sabina Fehric, Gautier Marcq, Jose Joao Mansure, Fabio Cury, Fadi Brimo, Ciriaco A Piccirillo, Wassim Kassouf","doi":"10.1080/15384047.2024.2365452","DOIUrl":"10.1080/15384047.2024.2365452","url":null,"abstract":"<p><p>MIBC is a highly lethal disease, and the patient survival rate has not improved significantly over the last decades. UPPL is a cell line that can be used to recapitulate the luminal-like molecular subtype of bladder cancer and to discover effective treatments to be translated in patients. Here, we investigate the effects of combinational treatments of radiotherapy and immunotherapy in this recently characterized UPPL tumor-bearing mice. We first characterized the baseline tumor microenvironment and the effect of radiation, anti-PD-L1, and combinatorial treatments. Then, the mice were re-challenged with a second tumor (rechallenged tumor) in the contralateral flank of the first tumor to assess the immunological memory. Radiation slowed down the tumor growth. All treatments also decreased the neutrophil population and increased the T cell population. Anti-PD-L1 therapy was not able to synergize with radiation to further delay tumor growth. Furthermore, none of the treatments were able to generate immune memory. The treatments were not sufficient to induce a significant and lasting pool of memory cells. We show here that anti-PD-L1 treatment added to radiotherapy was not enough to achieve T cell-mediated memory in UPPL tumors. Stronger T cell activation signals may be required to enhance radiation efficacy in luminal-like bladder cancer.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11174127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-31Epub Date: 2024-05-14DOI: 10.1080/15384047.2024.2343450
Anyu Luo, Hanlin Liu, Chen Huang, Sheng Wei
The potential function and mechanism of circRNAs in regulating malignant performances of Osteosarcoma (OS) cells have not been well investigated. The expression level of CircLMO7, miR-21-5p and ARHGAP24 were detected by RT-qPCR. The relationship between miR-21-5p and circ-LMO7, as well as between miR-21-5p and ARHGAP24, was predicted and examined through bioinformatics analysis and luciferase reporter gene experiments. Moreover, OS cell growth, invasion, migration, and apoptosis were detected using the cell counting kit-8 (CCK-8), transwell and flow cytometry assays, respectively. ARHGAP24 protein level was measured using western blotting. In present study, we choose to investigate the role and mechanism of circ-LOM7 on OS cell proliferation, migration and invasion. circ-LOM7 was found to be down-regulated in OS tissues and cell lines. Enforced expression of circ-LOM7 suppressed the growth, invasion, and migration of OS cells. In contrast, decreasing circ-LMO7 expression had opposite effects. Furthermore, miR-21-5p was predicted to be sponged by circ-LMO7, and had an opposite role of circ-LMO7 in OS. Moreover, ARHGAP24 served as miR-21-5p's downstream target. Mechanistically, circ-LMO7 was packed in exosomes and acted as a cancer-suppresser on OS by sponging miR-21-5p and upregulating the expression of ARHGAP24. The exosomal circ-LMO7 expression was significantly decreased in OS cell exosomes, and co-culture experiments showed that exosomal circ-LMO7 suppressed the proliferation ability of OS cells. Circ-LMO7 exerts as a tumor suppressor in OS, and the circ-LMO7/miR-21-5P/ARHGAP24 axis is involved in OS progression.
{"title":"Exosome-transmitted circular RNA circ-LMO7 facilitates the progression of osteosarcoma by regulating miR-21-5p/ARHGAP24 axis.","authors":"Anyu Luo, Hanlin Liu, Chen Huang, Sheng Wei","doi":"10.1080/15384047.2024.2343450","DOIUrl":"10.1080/15384047.2024.2343450","url":null,"abstract":"<p><p>The potential function and mechanism of circRNAs in regulating malignant performances of Osteosarcoma (OS) cells have not been well investigated. The expression level of CircLMO7, miR-21-5p and ARHGAP24 were detected by RT-qPCR. The relationship between miR-21-5p and circ-LMO7, as well as between miR-21-5p and ARHGAP24, was predicted and examined through bioinformatics analysis and luciferase reporter gene experiments. Moreover, OS cell growth, invasion, migration, and apoptosis were detected using the cell counting kit-8 (CCK-8), transwell and flow cytometry assays, respectively. ARHGAP24 protein level was measured using western blotting. In present study, we choose to investigate the role and mechanism of circ-LOM7 on OS cell proliferation, migration and invasion. circ-LOM7 was found to be down-regulated in OS tissues and cell lines. Enforced expression of circ-LOM7 suppressed the growth, invasion, and migration of OS cells. In contrast, decreasing circ-LMO7 expression had opposite effects. Furthermore, miR-21-5p was predicted to be sponged by circ-LMO7, and had an opposite role of circ-LMO7 in OS. Moreover, ARHGAP24 served as miR-21-5p's downstream target. Mechanistically, circ-LMO7 was packed in exosomes and acted as a cancer-suppresser on OS by sponging miR-21-5p and upregulating the expression of ARHGAP24. The exosomal circ-LMO7 expression was significantly decreased in OS cell exosomes, and co-culture experiments showed that exosomal circ-LMO7 suppressed the proliferation ability of OS cells. Circ-LMO7 exerts as a tumor suppressor in OS, and the circ-LMO7/miR-21-5P/ARHGAP24 axis is involved in OS progression.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11095575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140920996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-31Epub Date: 2024-09-05DOI: 10.1080/15384047.2024.2398285
Haixin Mo, Xin Zhang, Liangliang Ren
Breast cancer stands as the most prevalent cancer diagnosed worldwide, often leading to brain metastasis, a challenging complication characterized by high mortality rates and a grim prognosis. Understanding the intricate mechanisms governing breast cancer brain metastasis (BCBM) remains an ongoing challenge. The unique microenvironment in the brain fosters an ideal setting for the colonization of breast cancer cells. The tumor microenvironment (TME) in brain metastases plays a pivotal role in the initiation and progression of BCBM, shaping the landscape for targeted therapeutic interventions. Current research primarily concentrates on unraveling the complexities of the TME in BCBM, with a particular emphasis on neuroglia and immune cells, such as microglia, monocyte-derived macrophages (MDMs), astrocytes and T cells. This comprehensive review delves deeply into these elements within the TME of BCBM, shedding light on their interplay, mechanisms, and potential as therapeutic targets to combat BCBM.
{"title":"Analysis of neuroglia and immune cells in the tumor microenvironment of breast cancer brain metastasis.","authors":"Haixin Mo, Xin Zhang, Liangliang Ren","doi":"10.1080/15384047.2024.2398285","DOIUrl":"10.1080/15384047.2024.2398285","url":null,"abstract":"<p><p>Breast cancer stands as the most prevalent cancer diagnosed worldwide, often leading to brain metastasis, a challenging complication characterized by high mortality rates and a grim prognosis. Understanding the intricate mechanisms governing breast cancer brain metastasis (BCBM) remains an ongoing challenge. The unique microenvironment in the brain fosters an ideal setting for the colonization of breast cancer cells. The tumor microenvironment (TME) in brain metastases plays a pivotal role in the initiation and progression of BCBM, shaping the landscape for targeted therapeutic interventions. Current research primarily concentrates on unraveling the complexities of the TME in BCBM, with a particular emphasis on neuroglia and immune cells, such as microglia, monocyte-derived macrophages (MDMs), astrocytes and T cells. This comprehensive review delves deeply into these elements within the TME of BCBM, shedding light on their interplay, mechanisms, and potential as therapeutic targets to combat BCBM.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11382727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P4HA2 has been implicated in various malignant tumors; however, its expression and functional role in colorectal cancer (CRC) remain poorly elucidated. This study aims to investigate the involvement of P4HA2 in CRC metastasis and progression, uncovering the underlying mechanisms. In colorectal cancer (CRC), P4HA2 exhibited overexpression, and elevated levels of P4HA2 expression were associated with an unfavorable prognosis. Functional assays demonstrated P4HA2's regulation of cell proliferation, and epithelial-mesenchymal transition (EMT) both in vitro and in vivo. Additionally, the AGO1 expression was correlated with P4HA2, and depletion of AGO1 reversed the proliferation and EMT function induced by P4HA2. Chromatin immunoprecipitation (ChIP) and luciferase assays suggested that the transcription factor SP1 binds to the promoter sequence of P4HA2, activating its expression in CRC. This study unveiled SP1 as a transcriptional regulator of P4HA2 in CRC and AGO1 is a probable target of P4HA2. In conclusion, P4HA2 emerges as a potential prognostic biomarker and promising therapeutic target in colorectal cancer.
{"title":"P4HA2 promotes tumor progression and is transcriptionally regulated by SP1 in colorectal cancer.","authors":"Xuening Dang, Xiaojian Chen, Zhonglin Liang, Zhujiang Dai, Wenjun Ding, Jinglue Song, Jihong Fu","doi":"10.1080/15384047.2024.2361594","DOIUrl":"10.1080/15384047.2024.2361594","url":null,"abstract":"<p><p>P4HA2 has been implicated in various malignant tumors; however, its expression and functional role in colorectal cancer (CRC) remain poorly elucidated. This study aims to investigate the involvement of P4HA2 in CRC metastasis and progression, uncovering the underlying mechanisms. In colorectal cancer (CRC), P4HA2 exhibited overexpression, and elevated levels of P4HA2 expression were associated with an unfavorable prognosis. Functional assays demonstrated P4HA2's regulation of cell proliferation, and epithelial-mesenchymal transition (EMT) both in vitro and in vivo. Additionally, the AGO1 expression was correlated with P4HA2, and depletion of AGO1 reversed the proliferation and EMT function induced by P4HA2. Chromatin immunoprecipitation (ChIP) and luciferase assays suggested that the transcription factor SP1 binds to the promoter sequence of P4HA2, activating its expression in CRC. This study unveiled SP1 as a transcriptional regulator of P4HA2 in CRC and AGO1 is a probable target of P4HA2. In conclusion, P4HA2 emerges as a potential prognostic biomarker and promising therapeutic target in colorectal cancer.</p>","PeriodicalId":9536,"journal":{"name":"Cancer Biology & Therapy","volume":null,"pages":null},"PeriodicalIF":4.4,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11168210/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141295594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}