Cancer immunology, immunotherapy : CII最新文献

{"title":"Efficacy and safety of local-regional therapy combined with chemotherapy, immune checkpoint inhibitors and lenvatinib as first-line treatment in advanced intrahepatic cholangiocarcinoma: a multicenter retrospective cohort study.","authors":"Shuofeng Li, Guanhua Yu, Mingming Wang, Shi Feng, Shanshan Wang, Mingjian Piao, Chengjie Li, Zixiang Zhou, Ziyu Xun, Boyu Sun, Jiongyuan Li, Nan Zhang, Hu Li, Xiaobo Yang, Zhenyu Zhu, Haitao Zhao","doi":"10.1007/s00262-025-04085-1","DOIUrl":"10.1007/s00262-025-04085-1","url":null,"abstract":"<p><strong>Background: </strong>Local-regional therapy combined with immune checkpoint inhibitors (ICIs) and lenvatinib has shown promising anti-tumor activity in advanced biliary tract cancer. However, the efficacy and safety of integrating local-regional therapy with chemotherapy, ICIs, and lenvatinib in advanced intrahepatic cholangiocarcinoma (ICC) remain unclear. This study evaluated the efficacy and safety of first-line treatment combining local-regional therapy, chemotherapy, ICIs, and lenvatinib in advanced ICC.</p><p><strong>Methods: </strong>This multicenter study included 47 advanced ICC patients receiving local-regional therapy (radiotherapy, hepatic arterial infusion chemotherapy, or transarterial chemoembolization) plus chemotherapy, ICIs, and lenvatinib from October 2019 to January 2025. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), adverse events (AEs), and prognostic factors analysis.</p><p><strong>Results: </strong>The multimodal therapy demonstrated mPFS of 10.2 months and mOS of 20.2 months. ORR and DCR reached 61.7% and 93.6%, respectively. Conversion surgery was performed in 10.6% (5/47) of patients, with 60.0% (3/5) achieving sustained remission. All patients experienced AEs, with grade 3-4 AEs in 66.0%, primarily including myelosuppression (23.4%), AST or ALT increased (19.1%), fatigue (14.9%), and pain (10.6%). No grade 5 AEs were observed, and all toxicities were manageable. Survival outcomes, tumor response rates, and grade 3-4 AE incidence showed no significant differences among local-regional therapy subgroups. Multivariate analyses identified impaired performance status as an independent predictor of poorer OS.</p><p><strong>Conclusions: </strong>The combined regimen of local-regional therapy, chemotherapy, ICIs, and lenvatinib exhibited marked efficacy and a tolerable safety profile, establishing it as a viable first-line approach for advanced ICC.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 7","pages":"229"},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125452/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of innate lymphoid cell type 2 in chronic lymphocytic leukemia on the function of treg and CD8⁺ T cells through IL-9.","authors":"Ruixue Yang, Xuejiao Zeng, Xierenguli Alimu, Jianhua Qu","doi":"10.1007/s00262-025-04082-4","DOIUrl":"10.1007/s00262-025-04082-4","url":null,"abstract":"<p><strong>Objective: </strong>This study investigated the impact of innate lymphoid cell type 2 (ILC2s) on the function of regulatory T cells (Treg) and CD8⁺ T cells in chronic lymphocytic leukemia (CLL) through IL-9.</p><p><strong>Methods: </strong>Peripheral blood samples were collected from CLL patients (n = 52) and healthy controls (n = 30). ILC2 proportions and IL-9 levels were assessed using flow cytometry and ELISA. Immunofluorescence staining was performed to stain GATA3, CRTH2, and IL-9 in cervical lymph nodes from CLL patients (n = 10) and control subjects with reactive lymphadenitis (n = 10). Correlation analysis between ILC2s and IL-9 was conducted using the Spearman test. ILC2s were sorted and cultured from CLL patients, followed by co-culture experiments with PBMCs of healthy controls and MEC-1 cells, with or without anti-IL-9 antibody intervention. Flow cytometry was used to measure the proportions of ILC2s, Treg cells, PD-1⁺/TIGIT⁺/CTLA-4⁺ Treg subsets, and granzyme B⁺/perforin⁺ CD8⁺ T cells, along with MEC-1 cell apoptosis.</p><p><strong>Results: </strong>The proportions of ILC2s and Treg, along with serum IL-9 levels, were significantly elevated in CLL patients (P < 0.05). Peripheral blood ILC2s were positively correlated with IL-9 (r = 0.609, P < 0.001). The average fluorescence intensity of GATA3, CRTH2, and IL-9 in the cervical lymph nodes of CLL patients increased significantly (P < 0.001), and IL-9 showed colocalization with GATA3 and CRTH2. In vitro, IL-9 levels in the supernatant of sorted ILC2s from CLL patients increased. Treatment with anti-IL-9 antibody significantly reduced the PD-1⁺ Treg and TIGIT⁺ Treg cells while increasing granzyme B⁺ CD8⁺ T cells (P < 0.05). However, there was no significant effect on Treg, CTLA-4⁺ Treg, and perforin⁺ CD8⁺ T cells (P > 0.05). Additionally, anti-IL-9 antibody significantly increased early apoptosis (P < 0.05).</p><p><strong>Conclusion: </strong>ILC2s affect CD8⁺ T cells and Treg cells through IL-9, weakening the anti-tumor effects of CD8⁺ T cells and enhancing the immunosuppressive effects of Treg cells, thereby contributing to CLL pathogenesis.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 7","pages":"228"},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125456/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of head and neck squamous cell carcinoma by Bruton's tyrosine kinase inhibitor ibrutinib is associated with reduction of immunosuppressive T cells.","authors":"Anna R Bopp, Felipe F Lamenza, Puja Upadhaya, Nathan M Ryan, Natalie Kazmierowicz, Pete P Jordanides, Arham Siddiqui, Sherefuddin H Pracha, Peyton Roth, O Hans Iwenofu, Steve Oghumu","doi":"10.1007/s00262-025-04081-5","DOIUrl":"10.1007/s00262-025-04081-5","url":null,"abstract":"<p><p>Head and neck squamous cell carcinoma (HNSCC) is one of the most diagnosed malignancies globally, with a 5-year survival rate of only 40-50%. Current therapies are limited to aggressive chemoradiotherapy combinations and disfiguring resection. Recent research has demonstrated that inhibition of Bruton's tyrosine kinase (BTK) by ibrutinib is an effective treatment for aggressive solid cancers. However, little is known about the effects of ibrutinib on aggressive HNSCC. We tested the efficacy of ibrutinib against HNSCC in vitro and in a metastatic, aggressive MOC2 orthotopic murine model and determined the underlying mechanisms. Ibrutinib decreased cancer cell growth in vitro, reduced tumor burden in vivo, decreased metastasis to the tumor draining lymph nodes and lungs, and enhanced overall survival outcomes. Flow cytometric analysis revealed decreased infiltration of tumor-infiltrating immunosuppressive T cells expressing the co-inhibitory markers PD-1, LAG-3, and IL-10. Furthermore, ibrutinib treatment increased cytotoxic T cell infiltration into the tumor microenvironment. Further analysis demonstrated that the effects on immunosuppressive T cell phenotypes were directly mediated by ibrutinib. Immunosuppressive myeloid cells were also observed to express lower levels of PDL1 in ibrutinib-treated mice. Our study demonstrates the potential of BTK inhibitors, specifically ibrutinib, in the treatment of HNSCC, mediated by its inhibitory effect on HNSCC cancer cell growth and metastasis, as well as modulation of the T cell anti-tumor immune microenvironment.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 7","pages":"227"},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125455/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic significance of osteosarcopenia and its effects on immune response in patients with stage II/III gastric cancer.","authors":"Yuki Hirase, Takaaki Arigami, Daisuke Matsushita, Masataka Shimonosono, Yusuke Tsuruda, Ken Sasaki, Kenji Baba, Yota Kawasaki, Takao Ohtsuka","doi":"10.1007/s00262-025-04084-2","DOIUrl":"10.1007/s00262-025-04084-2","url":null,"abstract":"<p><strong>Background: </strong>Osteosarcopenia, characterized by muscle loss and osteoporosis, has emerged as a prognostic marker for various malignancies. However, its impact on the immune response in gastric cancer remains unclear. This study aimed to assess the clinical significance of osteosarcopenia and its relationship with the immune microenvironment in patients with advanced gastric cancer.</p><p><strong>Methods: </strong>This study included 105 patients with pathological stage II/III gastric cancer who underwent gastrectomy between 2018 and 2022. Preoperative computed tomography was used to measure muscle mass and bone density, with sarcopenia and osteoporosis defined as values below the respective standard thresholds. Sarcopenia and osteoporosis were identified when both conditions were present. We explored the relationships between osteosarcopenia, clinicopathological factors, and prognoses. Additionally, immune marker expression was evaluated via immunohistochemistry.</p><p><strong>Results: </strong>Among the 105 patients, 37 (35%) were diagnosed with osteosarcopenia. This condition significantly correlated with performance status, body mass index, and disease recurrence (all p < 0.05). Overall survival and relapse-free survival were significantly lower in the osteosarcopenia group than those in the non-osteosarcopenia group (all p < 0.05). Moreover, the osteosarcopenia group had significantly fewer CD8-positive, programmed cell death protein 1-positive, and programmed death-ligand 1-positive cells than that of the control group (all p < 0.05).</p><p><strong>Conclusions: </strong>Our findings suggest that osteosarcopenia is associated with the tumor microenvironment and might serve as a prognostic indicator in patients with advanced gastric cancer.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 7","pages":"230"},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125429/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stabilized iRGD modification enhances NY-ESO-1 TCR-T infiltration in solid tumors and synergizes with PD-1 blockade.","authors":"Yirong Wu, Lanqun Qin, Jiayu Wang, Ziyao Xie, Xinyu Su, Xiang Li, Yueling Yang, Rong Huang, Mengke Zhao, Lianjun Zhao, Zhengyun Zou","doi":"10.1007/s00262-025-04077-1","DOIUrl":"10.1007/s00262-025-04077-1","url":null,"abstract":"<p><p>Currently, two main challenges in cancer immunotherapy commonly hinder the application of T cell receptor-modified T cell (TCR-T) therapy in the treatment of solid tumors, including the limited ability of T cells to infiltrate solid tumor tissues and the immunosuppressive signals that restrain the anti-tumor efficacy of T cells. In this study, we constructed NY-ESO-1-specific TCR-T and introduced polyethylene glycol-phospholipids (PEG-lipids) to stably modify NY-ESO-1 TCR-T with nonapeptide iRGD, aiming to enhance the penetrability of T cells in vivo, then we combined iRGD-modified NY-ESO-1 TCR-T (iRGD-NY-ESO-1 TCR-T) with PD-1 blockade to alleviate immunosuppressive signals. In result, it is suggested that stably modifying NY-ESO-1 TCR-T with iRGD is a simple and effective strategy to enable TCR-T to target and penetrate solid tumor tissues. Besides, the combination of iRGD-NY-ESO-1 TCR-T with PD-1 blockade presents a novel synergistic strategy for the treatment of refractory NY-ESO-1-positive solid tumors.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 7","pages":"226"},"PeriodicalIF":0.0,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12125417/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144188767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chaperonin containing TCP1 subunit 5 as a novel pan-cancer prognostic biomarker for tumor stemness and immunotherapy response: insights from multi-omics data, integrated machine learning, and experimental validation.","authors":"Jiajun Li, Nuo Xu, Leyin Hu, Jiayue Xu, Yifan Huang, Deqi Wang, Feng Chen, Yi Wang, Jiani Jiang, Yanggang Hong, Huajun Ye","doi":"10.1007/s00262-025-04071-7","DOIUrl":"10.1007/s00262-025-04071-7","url":null,"abstract":"<p><strong>Background: </strong>Chaperonin containing TCP1 subunit 5 (CCT5), a vital component of the molecular chaperonin complex, has been implicated in tumorigenesis, cancer stemness maintenance, and therapeutic resistance. Nevertheless, its comprehensive roles in pan-cancer progression, underlying biological functions, and potential as a predictor of immunotherapy response remains poorly understood.</p><p><strong>Methods: </strong>We performed a comprehensive multi-omics pan-cancer analysis of CCT5 across 33 cancer types, integrating bulk RNA-seq, single-cell RNA-seq (scRNA-seq), and spatial transcriptomics data. CCT5 expression patterns, prognostic relevance, stemness association, and immune microenvironment relationships were evaluated. A novel CCT5-based signature (CCT5.Sig) was developed using machine learning on 23 immune checkpoint blockade (ICB) cohorts (n = 1394) spanning eight cancer types. Model performance was assessed using AUC metrics and survival analyses.</p><p><strong>Results: </strong>CCT5 was significantly overexpressed in tumor tissues and primarily localized to malignant and cycling cells. High CCT5 expression correlated with poor prognosis in multiple cancers and was enriched in oncogenic, cell cycle, and DNA damage repair pathways. CCT5 expression was positively associated with mRNAsi, mDNAsi, and CytoTRACE scores, indicating a role in stemness maintenance. Furthermore, CCT5-high tumors exhibited immune-cold phenotypes, with reduced TILs and CD8⁺ T cell activity. The CCT5.Sig model, based on genes co-expressed with CCT5, achieved superior predictive accuracy for ICB response (AUC = 0.82 in validation and 0.76 in independent testing), outperforming existing pan-cancer signatures.</p><p><strong>Conclusion: </strong>This study reveals the multifaceted oncogenic roles of CCT5 and highlights its potential as a pan-cancer biomarker for prognosis and immunotherapy response. The machine learning-derived CCT5.Sig model provides a robust tool for patient stratification and may inform personalized immunotherapy strategies.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 7","pages":"224"},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116413/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Monitoring peripheral blood data supports the prediction of immunotherapy response in advanced non‑small cell lung cancer based on real‑world data.","authors":"Ana D Ramos-Guerra, Benito Farina, Jaime Rubio Pérez, Anna Vilalta-Lacarra, Jon Zugazagoitia, Germán Peces-Barba, Luis M Seijo, Luis Paz-Ares, Ignacio Gil-Bazo, Manuel Dómine Gómez, María J Ledesma-Carbayo","doi":"10.1007/s00262-025-04055-7","DOIUrl":"10.1007/s00262-025-04055-7","url":null,"abstract":"","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 7","pages":"222"},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153270","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pembrolizumab-axitinib versus nivolumab-cabozantinib as first-line therapy in patients with metastatic renal cell carcinoma: a retrospective real-world comparison (ARON-1).","authors":"Matteo Santoni, Giandomenico Roviello, Enrique Grande, Ugo De Giorgi, Ondrej Fiala, Emmanuel Seront, Javier Molina-Cerrillo, Renate Pichler, Zin W Myint, Jakub Kucharz, Ravindran Kanesvaran, Thomas Büttner, Martin Pichler, Umberto Basso, Jindrich Kopecky, Maria T Bourlon, Linda Cerbone, Tomas Buchler, Alvaro Pinto, Alfonso Gómez de Liaño, Caterina Gianni, Anca Zgura, Pasquale Rescigno, Jawaher Ansari, Orazio Caffo, Zsófia Küronya, Maria Giuseppa Vitale, Dipen Bhuva, Martina Catalano, Nuno Vau, Ray Manneh Kopp, Sebastiano Buti, Aristotelis Bamias, Camillo Porta, Kaisa Sunela, Francesco Massari","doi":"10.1007/s00262-025-04043-x","DOIUrl":"10.1007/s00262-025-04043-x","url":null,"abstract":"<p><strong>Background: </strong>The optimal first-line therapy for metastatic renal cell carcinoma (mRCC) remains uncertain, despite recent advancements in immune-based combinations. This retrospective study compares the effectiveness of pembrolizumab plus axitinib (PA) and nivolumab plus cabozantinib (NC) as first-line treatments for mRCC in a real-world setting.</p><p><strong>Methods: </strong>Patient data were collected from 55 centers across 16 countries, encompassing individuals diagnosed with mRCC receiving first-line treatment with PA or NC between January 2016 and October 2023. Clinical and tumor features and treatment responses were recorded. The primary endpoints were overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and time to second progression. Statistical analyses included Kaplan-Meier survival estimates, Cox proportional hazard models, and chi-square tests.</p><p><strong>Results: </strong>A total of 760 patients with a median age of 64 years (range, 29-88) were included. Of them, 607 received PA, and only 153 NC. In the overall study population, ORR was 59% for and 49% for PA. Median OS was 55.7 months and not reached (NR) for PA and NC, respectively (P = .51), while median PFS was longer with NC (27.6 months) than for PA (16.2 months, P = .003). Subgroup analysis suggested a PFS benefits for NC in male, younger patients, intermediate risk group, clear cell histology, and lung involvement, as well as ORR favored NC in good risk patients. Multivariate analysis identified first-line therapy as a significant factor associated with PFS.</p><p><strong>Conclusions: </strong>In this certainly biased retrospective comparison, NC demonstrated superior ORR and longer PFS compared to PA in mRCC. These findings underscore the importance of considering individual patient characteristics and risk profiles when selecting first-line therapy for mRCC.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 7","pages":"225"},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Normalization of tumor vasculature by imiquimod: proposal for a new anticancer therapeutic indication for a TLR7 agonist.","authors":"Magdalena Jarosz-Biej, Justyna Czapla, Joanna Ciepła, Ryszard Smolarczyk, Alina Drzyzga, Dorota Sprus-Lipka, Ewelina Pilny, Sybilla Matuszczak, Tomasz Cichoń","doi":"10.1007/s00262-025-04062-8","DOIUrl":"10.1007/s00262-025-04062-8","url":null,"abstract":"","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 7","pages":"223"},"PeriodicalIF":0.0,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12116976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotyping of thyroid cancer for clinical outcomes and implications.","authors":"Jin Xu, Zhen Luo, Dayong Xu, Mujing Ke, Cheng Tan","doi":"10.1007/s00262-025-04061-9","DOIUrl":"10.1007/s00262-025-04061-9","url":null,"abstract":"<p><strong>Background: </strong>Tumor immune microenvironment (TIME) plays a crucial role in cancer development. However, the prognostic significance of immune-related genes (IRGs) in thyroid cancer (THCA) is unclear.</p><p><strong>Methods: </strong>The Cancer Genome Atlas (TCGA)-THCA dataset was downloaded. The CIBERSORT algorithm was used to determine immune cell infiltration and a Weighted Gene Co-expression Network Analysis (WGCNA) was executed to obtain immune cell-related genes. Univariate Cox analysis was performed to screen prognostic genes and THCA samples were categorized into different immune cell-related clusters. The correlations between clusters and THCA prognosis and clinical characteristics were explored. Differentially expressed genes (DEGs) between THCA and controls from TCGA-THCA were identified. Macrophage and lymphocyte abundances, IFN-γ, wound healing, and TGF-beta levels were determined using the single set gene set enrichment analysis (GSEA), and THCA samples were categorized into different immune-related clusters, and corresponding genes were obtained from WGCNA. DEGs, IRGs, and immune-related clusters genes were subjected to overlap analysis to obtain differentially expressed IRGs (DE-IRGs), and these were subjected to least absolute shrinkage and selection operator (LASSO) and multivariate Cox analyses to identify prognosis-related genes. THCA samples were divided into high/low-risk groups based on the median risk score. Furthermore, the prognostic model's utility in predicting immunotherapy response was analyzed. The potential therapeutic drugs were obtained. The expression of the corresponding genes in 10 pairs of clinical specimens was evaluated and those of proteins were analyzed by immunofluorescence assay.</p><p><strong>Results: </strong>TCGA-THCA samples were categorized into two immune cell-related clusters based on 141 prognostic immune cell-related genes. Significant differences in survival and clinical characteristics such as T Stage between clusters. In total, 16,648 DEGs between THCA and control samples were extracted. THCA samples were categorized into two immune-related clusters and were found to affect the prognosis and TIME of THCA. By using LASSO and multivariate Cox analyses for 88 DE-IRGs, three prognostic IRGs, namely FLNC, IL18, and MMP17 were identified. The TIDE score of the low-risk group was significantly lower than that of the other one, indicating that these samples were more responsive to immunotherapy. The 50% inhibitory concentration (IC50) of camptothecin, methotrexate, rapamycin, and others were notably different between the risk groups.</p><p><strong>Conclusion: </strong>Based on bioinformatics analysis, we constructed an immune-related prognosis model for THCA, which is expected to provide new ideas for studies related to the prognosis and treatment of THCA.</p>","PeriodicalId":520581,"journal":{"name":"Cancer immunology, immunotherapy : CII","volume":"74 7","pages":"221"},"PeriodicalIF":0.0,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106169/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}