Journal of Experimental & Clinical Cancer Research最新文献

{"title":"Correction: CD147 promotes collective invasion through cathepsin B in hepatocellular carcinoma.","authors":"Shi-Jie Wang, Dong Chao, Wei Wei, Gang Nan, Jia-Yue Li, Fen-Ling Liu, Ling Li, Jian-Li Jiang, Hong-Yong Cui, Zhi-Nan Chen","doi":"10.1186/s13046-024-03246-x","DOIUrl":"10.1186/s13046-024-03246-x","url":null,"abstract":"","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"43 1","pages":"320"},"PeriodicalIF":11.4,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142830751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cryoablation-induced neutrophil Ca²⁺ elevation and NET formation exacerbate immune escape in colorectal cancer liver metastasis.","authors":"Hongtong Tan, Yiquan Jiang, Lujun Shen, Gulijiayina Nuerhashi, Chunyong Wen, Ling Gu, Yujia Wang, Han Qi, Fei Cao, Tao Huang, Ying Liu, Weining Xie, Wuguo Deng, Weijun Fan","doi":"10.1186/s13046-024-03244-z","DOIUrl":"10.1186/s13046-024-03244-z","url":null,"abstract":"<p><strong>Background: </strong>Liver metastasis poses a significant barrier to effective immunotherapy in patients with colorectal cancer. Cryoablation has emerged as a vital supplementary therapeutic approach for these patients. However, its impact on the tumor microenvironment following the ablation of liver metastases remains unclear.</p><p><strong>Methods: </strong>We acquired multi-omics time-series data at 1 day, 5 days, and 14 days post-cryoablation, based on tumor and peripheral blood samples from clinical patients, cell co-culture models, and a liver metastases mouse model built on the MC38 cell line in C57BL/6 J mice. This dataset included single-cell transcriptomic sequencing, bulk tissue transcriptomic sequencing, 4D-Label-Free proteomics, flow cytometry data, western blot data, and histological immunofluorescence staining of pathological specimens.</p><p><strong>Results: </strong>We found that a neutrophil-related inflammatory state persisted for at least 14 days post-cryoablation. During this period, neutrophils underwent phenotypic changes, shifting from the N1 to the N2 type. Cryoablation also caused a significant increase in intracellular Ca²⁺ concentration in neutrophils, which triggered the formation of PAD4-dependent neutrophil extracellular traps (NETs), further promoting immune evasion. Moreover, animal studies demonstrated that depleting or inhibiting the CXCL2-CXCR2 signaling axis within neutrophils, or degrading NETs, could effectively restore the host's anti-tumor immune response.</p><p><strong>Conclusions: </strong>These findings underscore the critical role of neutrophils and their NETs in immune escape following cryoablation. Targeting the CXCL2-CXCR2-Ca²⁺-PAD4 axis could enhance the therapeutic response to PD-1 antibodies, providing a potential strategy to improve treatment outcomes for colorectal cancer with liver metastases.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"43 1","pages":"319"},"PeriodicalIF":11.4,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142796376","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of the chemokine receptors CXCR1 and CXCR2 synergizes with docetaxel for effective tumor control and remodeling of the immune microenvironment of HPV-negative head and neck cancer models.","authors":"Lucas A Horn, Hanne Lind, Kristen Fousek, Haiyan Qin, Nika Rajabian, Shantel Angstadt, Nicole Hsiao-Sanchez, Miriam M Medina-Enriquez, Marcus D Kelly, Clint T Allen, Sarah M Hammoudeh, Roberto Weigert, Dean Y Maeda, John A Zebala, Claudia Palena","doi":"10.1186/s13046-024-03240-3","DOIUrl":"10.1186/s13046-024-03240-3","url":null,"abstract":"<p><strong>Background: </strong>Relapsed head and neck squamous cell carcinoma (HNSCC) unrelated to HPV infection carries a poor prognosis. Novel approaches are needed to improve the clinical outcome and prolong survival in this patient population which has poor long-term responses to immune checkpoint blockade. This study evaluated the chemokine receptors CXCR1 and CXCR2 as potential novel targets for the treatment of HPV-negative HNSCC.</p><p><strong>Methods: </strong>Expression of IL-8, CXCR1, and CXCR2 was investigated in HNSCC tissues and human cell line models. Inhibition of CXCR1/2 with the clinical stage, small molecule inhibitor, SX-682, was evaluated in vitro and in vivo using human xenografts and murine models of HNSCC, both as a monotherapy and in combination with the taxane chemotherapy, docetaxel.</p><p><strong>Results: </strong>High levels of IL-8, CXCR1, and CXCR2 expression were observed in HPV-negative compared to HPV-positive HNSCC tumors or cell lines. Treatment of HPV-negative HNSCC cell lines in vitro with SX-682 sensitized the tumor cells to the cytotoxic activity of docetaxel. In vivo, treatment of HNSCC xenograft models with the combination of SX-682 plus docetaxel led to strong anti-tumor control resulting in tumor cures. This phenomenon was associated with an increase of microRNA-200c and a decreased expression of its target, tubulin beta-3, a protein involved in resistance to microtubule-targeting chemotherapies. In vivo treatment of a murine syngeneic model of HNSCC with SX-682 plus docetaxel led to potent anti-tumor efficacy through a simultaneous decrease in suppressive CXCR2⁺ polymorphonuclear, myeloid-derived suppressor cells and an increase in cytotoxic CD8⁺ T cells in the combination therapy treated tumors compared to controls.</p><p><strong>Conclusions: </strong>This study reports, for the first time, mechanistic findings through which the combination of CXCR1/2 inhibition and docetaxel chemotherapy exhibits synergy in models of HPV-negative HNSCC. These findings provide rationale for the use of this novel combination approach to treat HPV-negative HNSCC patients and for future combination studies of CXCR1/2 inhibition, docetaxel, and immune-based therapies.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"43 1","pages":"318"},"PeriodicalIF":11.4,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11619435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142787553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Receptor tyrosine kinase inhibition leads to regression of acral melanoma by targeting the tumor microenvironment.","authors":"Eric A Smith, Rachel L Belote, Nelly M Cruz, Tarek E Moustafa, Carly A Becker, Amanda Jiang, Shukran Alizada, Anastasia Prokofyeva, Tsz Yin Chan, Tori A Seasor, Michael Balatico, Emilio Cortes-Sanchez, David H Lum, John R Hyngstrom, Hanlin Zeng, Dekker C Deacon, Allie H Grossmann, Richard M White, Thomas A Zangle, Robert L Judson-Torres","doi":"10.1186/s13046-024-03234-1","DOIUrl":"10.1186/s13046-024-03234-1","url":null,"abstract":"<p><strong>Background: </strong>Acral melanoma (AM) is an aggressive melanoma variant that arises from palmar, plantar, and nail unit melanocytes. Compared to non-acral cutaneous melanoma (CM), AM is biologically distinct, has an equal incidence across genetic ancestries, typically presents in advanced stage disease, is less responsive to therapy, and has an overall worse prognosis.</p><p><strong>Methods: </strong>An independent analysis of published sequencing data was performed to evaluate the frequency of receptor tyrosine kinase (RTK) ligands and adapter protein gene variants and expression. To target these genetic variants, a zebrafish acral melanoma model and preclinical patient-derived xenograft (PDX) mouse models were treated with a panel of RTK inhibitors. Residual PDX tumors were evaluated for changes in proliferation, vasculature, necrosis, and ferroptosis by histology and immunohistochemistry.</p><p><strong>Results: </strong>RTK ligands and adapter proteins are frequently amplified, translocated, and/or overexpressed in AM. Dual FGFR/VEGFR inhibitors decrease acral-analogous melanocyte proliferation and migration in zebrafish, and the potent pan-FGFR/VEGFR inhibitor, Lenvatinib, uniformly induces tumor regression in AM PDX tumors but only slows tumor growth in CM models. Unlike other multi-RTK inhibitors, Lenvatinib is not directly cytotoxic to dissociated AM PDX tumor cells and instead disrupts tumor architecture and vascular networks.</p><p><strong>Conclusion: </strong>Considering the great difficulty in establishing AM cell culture lines, these findings suggest that AM may be more sensitive to microenvironment perturbations than CM. In conclusion, dual FGFR/VEGFR inhibition may be a viable therapeutic strategy that targets the unique biology of AM.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"43 1","pages":"317"},"PeriodicalIF":11.4,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11613472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting PRMT5 through PROTAC for the treatment of triple-negative breast cancer.","authors":"Yaxun Guo, Yuzhan Li, Zhongmei Zhou, Lei Hou, Wenjing Liu, Wenlong Ren, Dazhao Mi, Jian Sun, Xueqin Dai, Yingying Wu, Zhuo Cheng, Tingyue Wu, Qianmei Luo, Cong Tian, Fubing Li, Zhigang Yu, Yihua Chen, Ceshi Chen","doi":"10.1186/s13046-024-03237-y","DOIUrl":"10.1186/s13046-024-03237-y","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) is currently the most aggressive subtype of breast cancer, characterized by high heterogeneity and strong invasiveness, and currently lacks effective therapies. PRMT5, a type II protein arginine methyltransferase, is upregulated in numerous cancers, including TNBC, and plays a critical role, marked it as an attractive therapeutic target. PROTAC (Proteolysis Targeting Chimeras) is an innovative drug development technology that utilizes the ubiquitin-proteasome system (UPS) to degrade target proteins, which is characterized by higher activity, enhanced safety, lower resistance, and reduced toxicity, offering significant value for clinical translation.</p><p><strong>Methods: </strong>This study utilizes the PROTAC technology to develop potential degraders targeting PRMT5 in vitro and in vivo.</p><p><strong>Results: </strong>Through the design, synthesis and screening of a series of targeted compounds, we identified YZ-836P as an effective compound that exerted cytotoxic effects and reduced the protein levels of PRMT5 and its key downstream target protein KLF5 in TNBC after 48 h. Its efficacy was significantly superior to the PRMT5 PROTAC degraders that had been reported. YZ-836P induced G1 phase cell cycle arrest and significantly induced apoptosis in TNBC cells. Additionally, we demonstrated that YZ-836P promoted the ubiquitination and degradation of PRMT5 in a cereblon (CRBN)-dependent manner. Notably, YZ-836P exhibited pronounced efficacy in inhibiting the growth of TNBC patient-derived organoids and xenografts in nude mice.</p><p><strong>Conclusions: </strong>These findings position YZ-836P as a promising candidate for advancing treatment modalities for TNBC.</p><p><strong>Trial registration: </strong>Ethics Committee of Yunnan Cancer Hospital, KYCS2023-078. Registered 7 June 2023.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"43 1","pages":"314"},"PeriodicalIF":11.4,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755829","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in non-small cell lung cancer mechanomedicine: deciphering the signaling networks that govern tumor-TME interactions.","authors":"Antonios N Gargalionis, Kostas A Papavassiliou, Efthimia K Basdra, Athanasios G Papavassiliou","doi":"10.1186/s13046-024-03242-1","DOIUrl":"https://doi.org/10.1186/s13046-024-03242-1","url":null,"abstract":"<p><p>Cells from the tumor microenvironment (TME) interact with tumor cells in non-small cell lung cancer (NSCLC) to form a reciprocal crosstalk which influences tumor growth, proliferation, metastasis and multidrug response. This crosstalk is modulated by TME mechanical inputs, which elicit the processes of mechanosensing and mechanotransduction. Recent advances in unveiling these signaling networks establish the interdisciplinary field of mechanomedicine to exploit emerging diagnostic, predictive and therapeutic tools for more effective NSCLC treatments.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"43 1","pages":"316"},"PeriodicalIF":11.4,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferroptosis and the tumor microenvironment.","authors":"Kaisa Cui, Kang Wang, Zhaohui Huang","doi":"10.1186/s13046-024-03235-0","DOIUrl":"10.1186/s13046-024-03235-0","url":null,"abstract":"<p><p>Ferroptosis is a type of regulated cell death characterized by its non-apoptotic, iron-dependent and oxidative nature. Since its discovery in 2012, extensive research has demonstrated its pivotal roles in tumorigenesis, metastasis and cancer therapy. The tumor microenvironment (TME) is a complex ecosystem comprising cancer cells, non-cancer cells, extracellular matrix, metabolites and cytokines. Recent studies have underscored a new paradigm in which non-cancer cells in the TME, such as immune and stromal cells, also play significant roles in regulating tumor progression and therapeutic resistance typically through complicated crosstalk with cancer cells. Notably, this crosstalk in the TME were partially mediated through ferrotopsis-related mechanisms. This review provides a comprehensive and systematic summary of the current findings concerning the roles of ferroptosis in the TME and how ferroptosis-mediated TME reprogramming impacts cancer therapeutic resistance and progression. Additionally, this review outlines various ferroptosis-related therapeutic strategies aimed at targeting the TME.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"43 1","pages":"315"},"PeriodicalIF":11.4,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11607824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AKT kinases as therapeutic targets.","authors":"Dalal Hassan, Craig W Menges, Joseph R Testa, Alfonso Bellacosa","doi":"10.1186/s13046-024-03207-4","DOIUrl":"10.1186/s13046-024-03207-4","url":null,"abstract":"<p><p>AKT, or protein kinase B, is a central node of the PI3K signaling pathway that is pivotal for a range of normal cellular physiologies that also underlie several pathological conditions, including inflammatory and autoimmune diseases, overgrowth syndromes, and neoplastic transformation. These pathologies, notably cancer, arise if either the activity of AKT or its positive or negative upstream or downstream regulators or effectors goes unchecked, superimposed on by its intersection with a slew of other pathways. Targeting the PI3K/AKT pathway is, therefore, a prudent countermeasure. AKT inhibitors have been tested in many clinical trials, primarily in combination with other drugs. While some have recently garnered attention for their favorable profile, concern over resistance and off-target effects have continued to hinder their widespread adoption in the clinic, mandating a discussion on alternative modes of targeting. In this review, we discuss isoform-centric targeting that may be more effective and less toxic than traditional pan-AKT inhibitors and its significance for disease prevention and treatment, including immunotherapy. We also touch on the emerging mutant- or allele-selective covalent allosteric AKT inhibitors (CAAIs), as well as indirect, novel AKT-targeting approaches, and end with a briefing on the ongoing quest for more reliable biomarkers predicting sensitivity and response to AKT inhibitors, and their current state of affairs.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"43 1","pages":"313"},"PeriodicalIF":11.4,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11606119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142755819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the role of TNFR2 signaling in the tumor microenvironment of breast cancer.","authors":"Ali Mussa, Nor Hayati Ismail, Mahasin Hamid, Mohammad A I Al-Hatamleh, Anthony Bragoli, Khalid Hajissa, Noor Fatmawati Mokhtar, Rohimah Mohamud, Vuk Uskoković, Rosline Hassan","doi":"10.1186/s13046-024-03218-1","DOIUrl":"10.1186/s13046-024-03218-1","url":null,"abstract":"<p><p>Breast cancer (BC) is the most frequently diagnosed malignancy among women. It is characterized by a high level of heterogeneity that emerges from the interaction of several cellular and soluble components in the tumor microenvironment (TME), such as cytokines, tumor cells and tumor-associated immune cells. Tumor necrosis factor (TNF) receptor 2 (TNFR2) appears to play a significant role in microenvironmental regulation, tumor progression, immune evasion, drug resistance, and metastasis of many types of cancer, including BC. However, the significance of TNFR2 in BC biology is not fully understood. This review provides an overview of TNFR2 biology, detailing its activation and its interactions with important signaling pathways in the TME (e.g., NF-κB, MAPK, and PI3K/Akt pathways). We discuss potential therapeutic strategies targeting TNFR2, with the aim of enhancing the antitumor immune response to BC. This review provides insights into role of TNFR2 as a major immune checkpoint for the future treatment of patients with BC.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"43 1","pages":"312"},"PeriodicalIF":11.4,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142752203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tailoring glioblastoma treatment based on longitudinal analysis of post-surgical tumor microenvironment.","authors":"Chiara Bastiancich, Emmanuel Snacel-Fazy, Samantha Fernandez, Stéphane Robert, Roberta Stacchini, Léa Plantureux, Sébastien Boissonneau, Benoit Testud, Benjamin Guillet, Franck Debarbieux, Hervé Luche, Dominique Figarella-Branger, Marie-Anne Estève, Emeline Tabouret, Aurélie Tchoghandjian","doi":"10.1186/s13046-024-03231-4","DOIUrl":"10.1186/s13046-024-03231-4","url":null,"abstract":"<p><p>Glioblastoma (GBM), an incurable primary brain tumor, typically requires surgical intervention followed by chemoradiation; however, recurrences remain fatal. Our previous work demonstrated that a nanomedicine hydrogel (GemC₁₂-LNC) delays recurrence when administered post-surgery. However, tumor debulking also triggers time-dependent immune reactions that promote recurrence at the resection cavity borders. We hypothesized that combining the hydrogel with an immunomodulatory drug could enhance therapeutic outcomes. A thorough characterization of the post-surgical microenvironment (SMe) is crucial to guide combinatorial approaches.In this study, we performed cellular resolution imaging, flow cytometry and spatial hyperplexed immunofluorescence imaging to characterize the SMe in a syngeneic mouse model of tumor resection. Owing to our dynamic approach, we observed transient opening of the blood-brain barrier (BBB) during the first week after surgery. BBB permeability post-surgery was also confirmed in GBM patients. In our murine model, we also observed changes in immune cell morphology and spatial location post-surgery over time in resected animals as well as the accumulation of reactive microglia and anti-inflammatory macrophages in recurrences compared to unresected tumors since the first steps of recurrence growth. Therefore we investigated whether starting a systemic treatment with the SMAC mimetic small molecule (GDC-0152) directly after surgery would be beneficial for enhancing microglial anti-tumoral activity and decreasing the number of anti-inflammatory macrophages around the GemC₁₂-LNC hydrogel-loaded tumor cavity. The immunomodulatory effects of this drug combination was firstly shown in patient-derived tumoroids. Its efficacy was confirmed in vivo by survival analysis and correlated with reversal of the immune profile as well as delayed tumor recurrence.This comprehensive study identified critical time frames and immune cellular targets within the SMe, aiding in the rational design of combination therapies to delay recurrence onset. Our findings suggest that post-surgical systemic injection of GDC-0152 in combination with GemC₁₂-LNC local treatment is a promising and innovative approach for managing GBM recurrence, with potential for future translation to human patient.</p>","PeriodicalId":50199,"journal":{"name":"Journal of Experimental & Clinical Cancer Research","volume":"43 1","pages":"311"},"PeriodicalIF":11.4,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11603899/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}