Ángel Bayón-Gil, Javier Martinez-Picado, Maria C Puertas
{"title":"Viremic non-progression in HIV/SIV infection: A tied game between virus and host.","authors":"Ángel Bayón-Gil, Javier Martinez-Picado, Maria C Puertas","doi":"10.1016/j.xcrm.2024.101921","DOIUrl":"https://doi.org/10.1016/j.xcrm.2024.101921","url":null,"abstract":"<p><p>High-efficacy antiretroviral treatment (ART) has been a game-changer for HIV/AIDS pandemic, but incomplete CD4<sup>+</sup> T cell recovery and persistent chronic immune activation still affect HIV-suppressed people. Exceptional cases of HIV infection that naturally exhibit delayed disease progression provide invaluable insights into protective biological mechanisms with potential clinical application. Viremic non-progressors (VNPs) represent an extremely rare population of individuals with HIV, characterized by preservation of the CD4<sup>+</sup> T cell compartment despite persistent high levels of viral load (>10,000 copies/mL). While only a few studies have investigated the immunovirological characteristics of adult and pediatric VNPs, most of our knowledge about this phenotype stems from its non-human-primate counterpart, the natural simian immunodeficiency virus (SIV) hosts. In this review, we synthesize the insights gained from recent studies of natural SIV hosts and VNPs and evaluate the potential similarities and differences in the mechanisms that underlie the absence of pathogenesis, with special focus on the control of immune activation.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":"6 1","pages":"101921"},"PeriodicalIF":11.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell Reports MedicinePub Date : 2025-01-21Epub Date: 2024-12-20DOI: 10.1016/j.xcrm.2024.101733
Benjamin M Jacobs, Christiane Gasperi, Sudhakar Reddy Kalluri, Raghda Al-Najjar, Mollie O McKeon, Jonathan Else, Albert Pukaj, Friederike Held, Stephen Sawcer, Maria Ban, Bernhard Hemmer
{"title":"Single-cell analysis of cerebrospinal fluid reveals common features of neuroinflammation.","authors":"Benjamin M Jacobs, Christiane Gasperi, Sudhakar Reddy Kalluri, Raghda Al-Najjar, Mollie O McKeon, Jonathan Else, Albert Pukaj, Friederike Held, Stephen Sawcer, Maria Ban, Bernhard Hemmer","doi":"10.1016/j.xcrm.2024.101733","DOIUrl":"10.1016/j.xcrm.2024.101733","url":null,"abstract":"<p><p>Neuroinflammation is often characterized by immune cell infiltrates in the cerebrospinal fluid (CSF). Here, we apply single-cell RNA sequencing to explore the functional characteristics of these cells in patients with various inflammatory, infectious, and non-inflammatory neurological disorders. We show that CSF is distinct from the peripheral blood in terms of both cellular composition and gene expression. We report that the cellular and transcriptional landscape of CSF is altered in neuroinflammation but is strikingly similar across different neuroinflammatory disorders. We find clonal expansion of CSF lymphocytes in all disorders but most pronounced in inflammatory diseases, and we functionally characterize the transcriptional features of these cells. Finally, we explore the genetic control of gene expression in CSF lymphocytes. Our results highlight the common features of immune cells in the CSF compartment across diverse neurological diseases and may help to identify new targets for drug development or repurposing in multiple sclerosis (MS).</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101733"},"PeriodicalIF":11.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell Reports MedicinePub Date : 2025-01-21Epub Date: 2024-12-19DOI: 10.1016/j.xcrm.2024.101872
Ian Miranda, Nusrat Jahan, Lalita A Shevde
{"title":"The metastatic cascade through the lens of therapeutic inhibition.","authors":"Ian Miranda, Nusrat Jahan, Lalita A Shevde","doi":"10.1016/j.xcrm.2024.101872","DOIUrl":"10.1016/j.xcrm.2024.101872","url":null,"abstract":"<p><p>Metastasis is a main cause of cancer-related death, and a deeper understanding of the metastatic process will inform more targeted and mechanistic approaches that can abrogate challenges in treatment efficacy and toxicity. Several steps throughout the metastatic cascade, from angiogenesis to secondary tumor formation, offer specific vulnerabilities to therapies that can lead to the decline or cessation of metastatic progression. A deeper understanding of the metastatic cascade also allows combination systemic therapies to be used synergistically. In this review, we describe current treatment modalities in the context of multiple steps of the metastatic cascade. We highlight their mechanisms and present their efficacy across multiple cancers. This work also presents targets within the metastatic cascade in need of more research that can advance the landscape of treatments and lead to the goal of metastatic cancer remission.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101872"},"PeriodicalIF":11.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell Reports MedicinePub Date : 2025-01-21Epub Date: 2024-12-27DOI: 10.1016/j.xcrm.2024.101882
Wee Loong Chin, Alistair M Cook, Jonathan Chee, Nicola Principe, Tracy S Hoang, Joel Kidman, Khaing P W Hmon, Yen Yeow, Matthew E Jones, Rui Hou, Elena Denisenko, Alison M McDonnell, Chung-Chau Hon, Jonathan Moody, Denise Anderson, Sonia Yip, Michelle M Cummins, Martin R Stockler, Peey-Sei Kok, Chris Brown, Thomas John, Steven C-H Kao, Deme J Karikios, Kenneth J O'Byrne, Brett G M Hughes, Richard A Lake, Alistair R R Forrest, Anna K Nowak, Timo Lassmann, W Joost Lesterhuis
{"title":"Coupling of response biomarkers between tumor and peripheral blood in patients undergoing chemoimmunotherapy.","authors":"Wee Loong Chin, Alistair M Cook, Jonathan Chee, Nicola Principe, Tracy S Hoang, Joel Kidman, Khaing P W Hmon, Yen Yeow, Matthew E Jones, Rui Hou, Elena Denisenko, Alison M McDonnell, Chung-Chau Hon, Jonathan Moody, Denise Anderson, Sonia Yip, Michelle M Cummins, Martin R Stockler, Peey-Sei Kok, Chris Brown, Thomas John, Steven C-H Kao, Deme J Karikios, Kenneth J O'Byrne, Brett G M Hughes, Richard A Lake, Alistair R R Forrest, Anna K Nowak, Timo Lassmann, W Joost Lesterhuis","doi":"10.1016/j.xcrm.2024.101882","DOIUrl":"10.1016/j.xcrm.2024.101882","url":null,"abstract":"<p><p>Platinum-based chemotherapy in combination with anti-PD-L1 antibodies has shown promising results in mesothelioma. However, the immunological mechanisms underlying its efficacy are not well understood and there are no predictive biomarkers to guide treatment decisions. Here, we combine time course RNA sequencing (RNA-seq) of peripheral blood mononuclear cells with pre-treatment tumor transcriptome data from the single-arm, phase 2 DREAM trial (N = 54). Single-cell RNA-seq and T cell receptor sequencing (TCR-seq) reveal that CD8<sup>+</sup> T effector memory (TEM) cells with stem-like properties are more abundant in peripheral blood of responders and that this population expands upon treatment. These peripheral blood changes are linked to the transcriptional state of the tumor microenvironment. Combining information from both compartments, rather than individually, is most predictive of response. Our study highlights complex interactions between the tumor and immune cells in peripheral blood during objective tumor responses to chemoimmunotherapy. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12616001170415.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101882"},"PeriodicalIF":11.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell Reports MedicinePub Date : 2025-01-21Epub Date: 2024-12-31DOI: 10.1016/j.xcrm.2024.101880
Alana A Arnone, Yu-Ting Tsai, J Mark Cline, Adam S Wilson, Brian Westwood, Meghan E Seger, Akiko Chiba, Marissa Howard-McNatt, Edward A Levine, Alexandra Thomas, David R Soto-Pantoja, Katherine L Cook
{"title":"Endocrine-targeting therapies shift the breast microbiome to reduce estrogen receptor-α breast cancer risk.","authors":"Alana A Arnone, Yu-Ting Tsai, J Mark Cline, Adam S Wilson, Brian Westwood, Meghan E Seger, Akiko Chiba, Marissa Howard-McNatt, Edward A Levine, Alexandra Thomas, David R Soto-Pantoja, Katherine L Cook","doi":"10.1016/j.xcrm.2024.101880","DOIUrl":"10.1016/j.xcrm.2024.101880","url":null,"abstract":"<p><p>Studies indicate that breast tissue has a distinct modifiable microbiome population. We demonstrate that endocrine-targeting therapies, such as tamoxifen, reshape the non-cancerous breast microbiome to influence tissue metabolism and reduce tumorigenesis. Using 16S sequencing, we found that tamoxifen alters β-diversity and increases Firmicutes abundance, including Lactobacillus spp., in mammary glands (MGs) of mice and non-human primates. Immunohistochemistry showed that lipoteichoic acid (LTA)-positive bacteria were elevated in tamoxifen-treated breast tissue. In B6.MMTV-PyMT mice, intra-nipple probiotic bacteria injections reduced tumorigenesis, altered metabolic gene expression, and decreased tumor proliferation. Probiotic-conditioned media selectively reduced viability in estrogen receptor-positive (ER+) breast cancer cells and altered mitochondrial metabolism in non-cancerous epithelial cells. Human tumor samples revealed that LTA-positive bacteria negatively correlated with Ki67, suggesting that endocrine therapies influence tumor-associated microbiota to regulate proliferation. Our data indicate that endocrine-targeting therapies modify the breast microbiome, corresponding with a shift in tissue metabolism to potentially reduce ER+ breast cancer risk.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101880"},"PeriodicalIF":11.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell Reports MedicinePub Date : 2025-01-21Epub Date: 2025-01-09DOI: 10.1016/j.xcrm.2024.101890
Ohuod Hawsawi, Weinan Xue, Tingting Du, Mengqi Guo, Xiaolin Yu, Mingyi Zhang, Paul S Hoffman, Roni Bollag, Jun Li, Jia Zhou, Hongbo Wang, Junran Zhang, Zheng Fu, Xiaoguang Chen, Chunhong Yan
{"title":"Mitochondrial uncouplers inhibit oncogenic E2F1 activity and prostate cancer growth.","authors":"Ohuod Hawsawi, Weinan Xue, Tingting Du, Mengqi Guo, Xiaolin Yu, Mingyi Zhang, Paul S Hoffman, Roni Bollag, Jun Li, Jia Zhou, Hongbo Wang, Junran Zhang, Zheng Fu, Xiaoguang Chen, Chunhong Yan","doi":"10.1016/j.xcrm.2024.101890","DOIUrl":"10.1016/j.xcrm.2024.101890","url":null,"abstract":"<p><p>Mitochondrial uncouplers dissipate proton gradients and deplete ATP production from oxidative phosphorylation (OXPHOS). While the growth of prostate cancer depends on OXPHOS-generated ATP, the oncogenic pathway mediated by the transcription factor E2F1 is crucial for the progression of this deadly disease. Here, we report that mitochondrial uncouplers, including tizoxanide (TIZ), the active metabolite of the Food and Drug Administration (FDA)-approved anthelmintic nitazoxanide (NTZ), inhibit E2F1-mediated expression of genes involved in cell cycle progression, DNA synthesis, and lipid synthesis. Consequently, NTZ/TIZ induces S-phase kinase-associated protein 2 (SKP2)-mediated G1 arrest while impeding DNA synthesis, lipogenesis, and the growth of prostate cancer cells. The anti-cancer activity of TIZ correlates with its OXPHOS-uncoupling activity. NTZ/TIZ appears to inhibit ATP production, thereby activating the AMP-activated kinase (AMPK)-p38 pathway, leading to cyclin D1 degradation, Rb dephosphorylation, and subsequent E2F1 inhibition. Our results thus connect OXPHOS uncoupling to the inhibition of an essential oncogenic pathway, supporting repositioning NTZ and other mitochondrial uncouplers for prostate cancer therapy.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101890"},"PeriodicalIF":11.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell Reports MedicinePub Date : 2025-01-21Epub Date: 2024-12-26DOI: 10.1016/j.xcrm.2024.101881
Ganji Purnachandra Nagaraju, Madhu Sudhana Saddala, Jeremy B Foote, Ateeq M Khaliq, Ashiq Masood, Yuvasri Golivi, Dhana Sekhar Reddy Bandi, Sujith Sarvesh, Sudhir Putty Reddy, Jeffrey Switchenko, Julienne L Carstens, Mehmet Akce, Cameron Herting, Olatunji B Alese, Karina J Yoon, Upender Manne, Manoj K Bhasin, Gregory B Lesinski, Vikas P Sukhatme, Bassel F El-Rayes
{"title":"Mechanism of enhancing chemotherapy efficacy in pancreatic ductal adenocarcinoma with paricalcitol and hydroxychloroquine.","authors":"Ganji Purnachandra Nagaraju, Madhu Sudhana Saddala, Jeremy B Foote, Ateeq M Khaliq, Ashiq Masood, Yuvasri Golivi, Dhana Sekhar Reddy Bandi, Sujith Sarvesh, Sudhir Putty Reddy, Jeffrey Switchenko, Julienne L Carstens, Mehmet Akce, Cameron Herting, Olatunji B Alese, Karina J Yoon, Upender Manne, Manoj K Bhasin, Gregory B Lesinski, Vikas P Sukhatme, Bassel F El-Rayes","doi":"10.1016/j.xcrm.2024.101881","DOIUrl":"10.1016/j.xcrm.2024.101881","url":null,"abstract":"<p><p>Pancreatic ductal adenocarcinoma (PDAC) has a minimal (<15%) 5-year existence, in part due to resistance to chemoradiotherapy. Previous research reveals the impact of paricalcitol (P) and hydroxychloroquine (H) on altering the lysosomal fusion, decreasing stromal burden, and triggering PDAC to chemotherapies. This investigation aims to elucidate the molecular properties of the H and P combination and their potential in sensitizing PDAC to gemcitabine (G). PH potentiates the effects of G in in vitro, orthotopic mouse models, and a patient-derived xenograft model of PDAC. Proteomic and single-cell RNA sequencing (RNA-seq) analyses reveal that GPH treatment upregulates autophagy and endoplasmic reticulum (ER) stress-related transcripts. GPH treatment decreases the number of Ki67, fibroblast-associated protein (FAP), and alpha-smooth muscle actin (SMA)-expressing fibroblasts with a decrease in autophagy-related transcripts. The GPH treatment increases M1 polarization and CD4<sup>+</sup> and CD8<sup>+</sup> T cells and reduces CD4<sup>+</sup> and CD8<sup>+</sup> regulatory T cells (Tregs). These effects of GPH were confirmed in paired biopsies obtained from patients treated in a clinical trial (NCT04524702).</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101881"},"PeriodicalIF":11.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"CD70-targeted iPSC-derived CAR-NK cells display potent function against tumors and alloreactive T cells.","authors":"Linqin Wang, Yiyun Wang, Xiangjun He, Zhuomao Mo, Mengyu Zhao, Xinghua Liang, Kejia Hu, Kexin Wang, Yanan Yue, Guolong Mo, Yixuan Zhou, Ruimin Hong, Linghui Zhou, Youqin Feng, Nian Chen, Lihong Shen, Xiaobin Song, Wenxiu Zeng, Xiaofeng Jia, Yuxuan Shao, Peng Zhang, Mengqi Xu, Dongrui Wang, Yongxian Hu, Luhan Yang, He Huang","doi":"10.1016/j.xcrm.2024.101889","DOIUrl":"10.1016/j.xcrm.2024.101889","url":null,"abstract":"<p><p>Clinical application of autologous chimeric antigen receptor (CAR)-T cells is complicated by limited targeting of cancer types, as well as the time-consuming and costly manufacturing process. We develop CD70-targeted, induced pluripotent stem cell-derived CAR-natural killer (NK) (70CAR-iNK) cells as an approach for universal immune cell therapy. Besides the CD70-targeted CAR molecule, 70CAR-iNK cells are modified with CD70 gene knockout, a high-affinity non-cleavable CD16 (hnCD16), and an interleukin (IL)-15 receptor α/IL-15 fusion protein (IL15RF). Multi-gene-edited 70CAR-iNK cells exhibit robust cytotoxicity against a wide range of tumors. In vivo xenograft models further demonstrate their potency in effectively targeting lymphoma and renal cancers. Furthermore, we find that recipient alloreactive T cells express high levels of CD70 and can be eliminated by 70CAR-iNK cells, leading to improved survival and persistence of iNK cells. With the capability of tumor targeting and the potential to eliminate alloreactive T cells, 70CAR-iNK cells are potent candidates for next-generation universal immune cell therapy.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101889"},"PeriodicalIF":11.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Phenotypic plasticity and increased infiltration of peripheral blood-derived TREM1<sup>+</sup> mono-macrophages following radiotherapy in rectal cancer.","authors":"Haihong Wang, Menglan Zhai, Mingjie Li, Chaoqun Han, Lichao Liu, Chuying Huang, Lei Zhao, Dandan Yu, Kaixiong Tao, Jinghua Ren, Zhenyu Lin, Tao Zhang","doi":"10.1016/j.xcrm.2024.101887","DOIUrl":"10.1016/j.xcrm.2024.101887","url":null,"abstract":"<p><p>In our previously reported phase 2 and phase 3 studies, the combination of short-course radiotherapy and neoadjuvant immunochemotherapy (SIC) is established as effective cancer therapies for locally advanced rectal cancer (LARC). Here, we apply multi-omic analyses to paired pre- and post-treatment LARC specimens undergoing SIC. The peripheral blood-derived TREM1<sup>+</sup> mono-macrophage subsets that display a pro-inflammatory phenotype are identified and correlate with complete response to SIC. Mechanically, ionizing radiation (IR) induces peripheral TREM1<sup>+</sup> mono-macrophage expansion in tumors. Following IR, the loss of TREM1 in mono-macrophages undermines antitumor immunity by altering mono-macrophage differentiation and inhibiting CD8<sup>+</sup> T cell infiltration and activation. The TREM1<sup>+</sup> mono-macrophage response may rely on activation of key inflammatory pathways, including nuclear factor κB (NF-κB) signaling and Toll-like receptor pathway. Pharmacological inhibition of TREM1 signaling abolishes IR-induced immunoactivation and reduces combined IR and/or anti-PD-1 treatment. Thus, we establish a crucial role of a mono-macrophage state in mediating effective cancer therapy.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101887"},"PeriodicalIF":11.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142964134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cell Reports MedicinePub Date : 2025-01-21Epub Date: 2024-12-20DOI: 10.1016/j.xcrm.2024.101877
Yang Chen, Hao Qin, Nan Li, Yaohua Wei, Yixuan Lin, Ronghui Deng, Hao Ding, Yuanyuan Lv, Tianyu Ma, Rong Li, Changhao Xiong, Guyu Zheng, Hanqing Chen, Jian Shi, Yuliang Zhao, Ruifang Zhao, Guangjun Nie
{"title":"Neoadjuvant chemotherapy by liposomal doxorubicin boosts immune protection of tumor membrane antigens-based nanovaccine.","authors":"Yang Chen, Hao Qin, Nan Li, Yaohua Wei, Yixuan Lin, Ronghui Deng, Hao Ding, Yuanyuan Lv, Tianyu Ma, Rong Li, Changhao Xiong, Guyu Zheng, Hanqing Chen, Jian Shi, Yuliang Zhao, Ruifang Zhao, Guangjun Nie","doi":"10.1016/j.xcrm.2024.101877","DOIUrl":"10.1016/j.xcrm.2024.101877","url":null,"abstract":"<p><p>Autologous tumor cell membrane antigen-based vaccines (TMVs) have garnered extensive attention as personalized immunotherapy. However, patients who take TMVs therapy usually undergo various treatments prior to surgery, and these processes modulate the immunogenicity of the tumor membrane and the tumor immune microenvironment. Herein, we investigate the impact of preoperative chemotherapy on the efficacy of TMVs. Liposomal doxorubicin ameliorates the immunosuppressive tumor microenvironment and enhances immunological molecule expression on the tumor membrane. This has driven TMVs to elicit a more robust immune response than doxorubicin, resulting in more effective immune protection. The TMVs formulated from liposomal doxorubicin-treated tumors induce superior dendritic cell maturation and T cell activation compared to doxorubicin, thus demonstrating better efficacy in preventing recurrence and metastasis in the postoperative murine model. Collectively, our study suggests that chemotherapy can induce immunomodulatory changes that augment the therapeutic potential of immunotherapy and provides valuable insights into the clinical utilization of TMVs.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":" ","pages":"101877"},"PeriodicalIF":11.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142871541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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