Endocrine-related cancer最新文献

{"title":"Local treatments and TKI efficacy in radioiodine refractory differentiated thyroid carcinoma patients: a single center experience.","authors":"Katerina Saltiki, Olga Karapanou, Kanella Kantreva, Marina Michalaki, Konstantinos Koutsoukos, Stavroula A Paschou, Maria Alevizaki","doi":"10.1530/ERC-24-0024","DOIUrl":"10.1530/ERC-24-0024","url":null,"abstract":"<p><p>A cohort of radioiodine-refractory differentiated thyroid cancer patients (RAI-R DTC) in a tertiary center underwent therapeutic interventions according to disease progression rate and metastasis location. We evaluated the independent impact of local and/or systemic treatments on final outcomes in 122 RAI-R DTC patients (44.3% men, age at diagnosis 51.98 ± 15.8 years) who were followed up for 9.5 years (1.4-50). Patients were divided into two groups: those with only locoregional persistent disease: group 1, n = 27 (22.1%) and those with distant metastases: group 2, n = 95 (77.9%). Patients from group 1 underwent mainly local procedures. The final outcome was 4/27 (14.8%) partial-response (PR) and 23/27 (85.2%) stable disease (SD). Of group 2 patients, 10/95 underwent active surveillance for micrometastatic disease, and the remaining received either only local treatments (40/95) or TKIs ± local treatments (45/95). The final outcome was PR in 7/95 (7.4%), SD in 38 (40%) and progressive disease in 50 (52.6%). Concerning group 2 in Kaplan-Meier analysis, local metastasis stabilization with local and/or systemic therapy had a favorable effect on survival (P < 0.02). Those treated with TKIs + local procedures, despite having more aggressive tumors, achieved more frequently local stabilization and had a similar outcome compared to those treated with only TKIs (P = 0.007). For group 2, in Cox proportional hazard analysis during the follow-up period, younger age at diagnosis and maintenance of tumor differentiation are predictors of more favorable OS and cancer-specific survival. In conclusion, the implementation of local procedures in RAI-R DTC management stabilizes metastatic lesions and potentially enhances survival. Further studies are warranted to validate these findings.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world outcomes of lenvatinib therapy for advanced neuroendocrine neoplasms.","authors":"Joao Paulo Solar Vasconcelos, Jose Eduardo Nunez Rodriguez, Ali Zaidi, Tharani Krishnan, Helia Jafari, Sharlene Gill, Ann Tan, Dan Le, Theresa Chan, Simon Yu, John Paul McGhie, Howard Lim, Simron Singh, Jonathan M Loree","doi":"10.1530/ERC-24-0292","DOIUrl":"10.1530/ERC-24-0292","url":null,"abstract":"<p><p>Advanced gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) constitute a heterogeneous group of incurable cancers. Lenvatinib is an oral multiple kinase inhibitor that showed activity in grade 1/2 GEP-NENs in the phase II TALENT trial, but a confirmatory phase III study has yet to be conducted. To investigate the real-world use of lenvatinib in treating patients with advanced GEP-NENs, we retrospectively analyzed a cohort of adults with unresectable neuroendocrine neoplasms (NENs) from two academic centers in Canada who received palliative treatment with lenvatinib. Progression-free survival (PFS), overall survival (OS) and the treating clinician assessment of best therapeutic response were analyzed in the entire cohort and in the subgroup of patients with GEP-NENs that would have been eligible for the TALENT trial. Overall, 33 patients, with mostly G1/G2 (78.8%) metastatic NENs, received lenvatinib. The pancreas was the most common primary site (n = 16, 48.5%), followed by the small bowel (n = 12, 36.4%). The median number of prior lines of systemic therapy was 2 (range 1-5). The median initial, maximal and minimal doses (mg) were 12 (range 4-24), 12 (range 8-24) and 8 (range 4-24), respectively. The median PFS was 11.9 months (95% CI, 9.5-NA), and the median OS was 17.5 months (95% CI, 12.7-NA), with disease burden reduction seen in 21.9% (95% CI, 11.0-38.7) and 87.5% (95% CI, 71.9-95.3) of patients achieving disease control. The most frequent side effects reported were hypertension (60.6%), fatigue (39.4%), hypothyroidism (21.2%) and diarrhea (18.2%). This real-world cohort demonstrates encouraging evidence of lenvatinib activity in metastatic NENs, even when used at lower doses than previously studied in NENs.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Management of high-grade neuroendocrine neoplasms: impact of functional imaging.","authors":"O Islam, K Sarti, L Verbruggen, V Vandersmissen, K Vanden Bulcke, L Annys, C Verslype, J L Van Laethem, H Rezaei Kalantari, J Janssens, A Hendlisz, P J Cuyle, G Demolin, J Decaestecker, K Geboes, J C Coche, J Van Ongeval, W Lybaert, M Peeters, I Borbath, T Vandamme","doi":"10.1530/ERC-24-0231","DOIUrl":"10.1530/ERC-24-0231","url":null,"abstract":"<p><p>Gastroenteropancreatic neuroendocrine neoplasms (GEP NEN) exhibit substantial biological heterogeneity, impacting clinical management and outcomes. In 2019, the WHO subdivided the grade 3 (G3) neuroendocrine neoplasms (NEN) characterised by Ki-67 > 20% into the well-differentiated G3 neuroendocrine tumour (NET) and G3 poorly differentiated neuroendocrine carcinoma (NEC) subgroups. Since this update, questions about the prognostic implications and best treatment strategies for NET G3 and NEC remain. Therefore, we initiated a real-world retrospective observational cohort study using data from 225 NEC and 58 NET G3 patients treated in Belgium. Analysis of patient and tumour characteristics and the effect of survival was conducted. Most frequent primary locations were pancreatic (32.9%) and colorectal (21.5%), and 71.8% was diagnosed with stage IV disease. Median overall survival (mOS) was higher in NET G3 (41.3 months (m)) compared to NEC (13.2m). Of those who underwent functional imaging, fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) imaging was positive in 90.6 and 95.6% of the NET G3 and NEC patients, respectively, and somatostatin receptor (SSTR) expression was seen in 97.4 and 66.0%, respectively. The latter was linked to better mOS, suggesting the added value of performing both SSTR imaging and 18F-FDG-PET for high-grade (HG) NEN to provide prognostic information and to possibly expand therapeutic options, which are currently reserved for lower-grade NEN patients. Moreover, while debated, in our population, primary surgery was performed in 92 and 73.5% of locoregional NET G3 and NEC cases, respectively, indicating that surgery can be considered in locoregional setting. Finally, platinum-etoposide was the predominant first-line treatment in metastatic NEC, with no significant survival difference between carboplatin and cisplatin.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spectrum and carcinogenic properties of thyroglobulin gene fusions in thyroid.","authors":"Gavin M Schmidt, Ian J Fornal, William R Doerfler, Abigail I Wald, Shannon E Keating, Marina N Nikiforova, Yuri E Nikiforov, Alyaksandr V Nikitski","doi":"10.1530/ERC-24-0334","DOIUrl":"10.1530/ERC-24-0334","url":null,"abstract":"<p><p>Approximately 10-20% of thyroid cancers are driven by gene fusions, which activate oncogenic signaling through aberrant overexpression, ligand-independent dimerization or loss of inhibitory motifs. We identified 13 thyroid tumors with thyroglobulin (TG) gene fusions and aimed to assess their histopathology and the fusions' oncogenic and tumorigenic properties. Of eleven cases with surgical pathology, 82% were carcinomas and 18% were noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP). TG fusions preserved exon(s) 1, 1-15, 1-35 or most frequently, 1-47 of TG and, based on the 3' partner were grouped as i) involving receptor tyrosine kinases (RTKs) (TG::FGFR1, TG::RET, TG::ALK and TG::NTRK1), ii) driving aberrant DPRX and chromosome 19 microRNA cluster expression (TG::DPRX) or iii) involving IGF2 mRNA-binding protein (TG::IGF2BP1). All 13 fusion-positive tumors exhibited strong (8.5 ± 3.3 log2-fold) 3' partner overexpression driven by the TG promoter. Gene expression analysis revealed TG::RET- and TG::ALK-positive tumors being BRAFV600E-like and remaining tumors RAS-like. In thyroid PCCL3 cells, the TG::NTRK1 fusion demonstrated both spontaneous and ligand-associated dimerization, activated downstream MAPK, AKT and STAT3 signaling and drove xenograft tumorigenesis in nude mice. FDA-approved NTRK inhibitors entrectinib and larotrectinib effectively blocked TG::NTRK1 signaling in vitro and inhibited xenograft tumor growth in vivo. In summary, we report a spectrum of TG gene fusions as recurrent oncogenic events in thyroid cancer and NIFTP that drive strong overexpression of partner genes, frequently RTKs. The TG::NTRK1 fusion is prone to dimerization, activates oncogenic signaling, drives tumorigenesis in thyroid cells and, like other fusions involving RTKs, represents a potential therapeutic target in thyroid cancer.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of long-acting recombinant human TSH using SAFA technology.","authors":"Daham Kim, Min Jeong Kang, So Jeong Lee, Yoon Hee Cho, Gunuk Zi, Jeongsuk An, Jinjoo Park, Jaekyu Han, Susan Chi, Sang-Hoon Cha, Eun Jig Lee","doi":"10.1530/ERC-24-0284","DOIUrl":"10.1530/ERC-24-0284","url":null,"abstract":"<p><p>Thyrogen, a recombinant human thyroid-stimulating hormone (rhTSH), has a short half-life in the bloodstream, which necessitates multiple doses during treatment. Therefore, we developed a new long-acting rhTSH using anti-serum albumin Fab-associated (SAFA) technology to validate its biological activity through in vitro assays, pharmacokinetic studies in healthy mice and pharmacodynamics studies in a thyroid-stimulating hormone (TSH)-suppressed mouse model. SAFA-TSH was produced using a Chinese hamster ovary expression system. To verify its biological activity, we generated Nthy-ori 3-1 cells stably overexpressing TSHR and measured the production of cyclic adenosine monophosphate (cAMP). In a rat study, slow-release triiodothyronine (T3) pellets were implanted 3 days before administering Thyrogen or SAFA-TSH to measure the amount of thyroxine (T4) release alone resulting from exogenous administration. SAFA-TSH increased cAMP production dose-dependently, but less effectively than Thyrogen at similar concentrations. SAFA-TSH required six times the dose of Thyrogen to achieve similar cAMP levels, likely due to differences in molecular weight and relative bioactivity. In a rat study, SAFA-TSH produced elevated thyroid hormone levels well after the decline in the response to Thyrogen. SAFA-TSH had significantly higher cumulative effects on T4 and free T4 levels compared with Thyrogen, as observed by a more than two-fold higher average area under the effect curve of 262.56 vs 118.89 μg × h/dL and 127.47 vs 60.75 μg × h/dL, respectively. SAFA technology created successful long-acting TSH that demonstrated bioactivity. These findings endorse the continued development of SAFA-TSH for clinical use, highlighting its potential as a significant advancement treating thyroid cancer patients.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143191629","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":"Global trends in thyroid cancer 1990-2021: an analysis based on the GBD 2021.","authors":"Tong Deng, Qing Liu, Hao Zi, Xingpei Guo, Qiao Huang, Yalong Yang, Lisha Luo, Jingxuan Hou, Rui Zhou, Qianqian Yuan, GaoSong Wu","doi":"10.1530/ERC-24-0297","DOIUrl":"10.1530/ERC-24-0297","url":null,"abstract":"<p><p>This study evaluated the global burden of thyroid cancer (TC) from 1990 to 2021, analyzing its association with sociodemographic factors, sex, age, risk factors and future projections. Using 2021 global burden of disease data, we analyzed TC incidence, mortality and disability-adjusted life years (DALYs) across populations. Risk factors were assessed, and future trends were forecasted using the Bayesian age-period-cohort model. In 2021, global TC incidence was 249,538 cases (age-standardized incidence rate (ASIR): 2.91 per 100,000). Mortality reached 44,799 cases, with a slight decrease in the age-standardized mortality rate (ASMR). DALYs increased by 92.73%, though the age-standardized DALY rate (ASDR) declined. East Asia had the highest incidence, while South Asia led in mortality and DALYs. TC burden showed a strong negative correlation with socioeconomic development, especially in high- and medium-sociodemographic index countries. High body mass index (BMI) contributed significantly to DALYs and mortality, particularly in the Middle East and North Africa. Population growth emerged as the key driver of the rising global TC burden. Projections suggest ASIR will increase by 2050, while ASMR and ASDR will decline. Global TC incidence has risen markedly, particularly among males, while mortality and DALYs have decreased due to improved healthcare. High BMI increasingly contributes to the TC burden. Projections highlight a continued rise in incidence but declining mortality and DALYs, reflecting advancements in treatment and management.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factors associated with grade progression in pancreatic neuroendocrine tumors.","authors":"Stephanie J Wang, Wesley Kidder, Nancy M Joseph, Bryan Khuong Le, Sheila Lindsay, Farhana Moon, Eric K Nakakura, Li Zhang, Emily K Bergsland","doi":"10.1530/ERC-24-0203","DOIUrl":"10.1530/ERC-24-0203","url":null,"abstract":"<p><p>Grade progression of well-differentiated pancreatic neuroendocrine tumors (panNETs) can occur over time, with G1/2 to G3 being the most clinically relevant form. Here, we conducted a retrospective cohort study of 66 patients with initially G1/2 panNET (median initial Ki67, 4.6%). Patients were followed up for a median 6.8 years and had a median of two metachronous tumor biopsies over their disease course. 34.8% of patients underwent any form of grade progression, including G1 to G2/3 and G2 to G3, while 24.2% demonstrated G1/2 to G3 grade progression. Over a median 2.3 years, G1/2 to G3 grade progressors experienced a median Ki67 change of +27.0% (range, +6.4 to +48.7%). Subsequent biopsies showing progression to G3 had a median Ki67 value of 31.0% (range, 21.0-60.0%) and were more often performed following suspicious clinical behavior (75.0%) rather than routinely at the time of scheduled procedure/surgery (25.0%). Similar to prior studies, G1/2 to G3 grade progressors had worse overall survival from the time of metastatic disease (median, 4.8 years vs not reached for stably G1/2 disease; P = 0.002). Heavier pretreatment and heterogeneity or lack of uptake on somatostatin receptor imaging was independently associated with progression to G3. In the largest study of metachronous panNET biopsies to date, our findings show that baseline biopsies suggesting G1/2 disease may not accurately reflect future disease status, highlighting the possible limitations of using archived tissue to stratify patients into trials and/or choose future therapy. Additional work is needed to better understand the impact of prior therapies on grade progression and how to identify which lesions to best follow up for repeat biopsy.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143018137","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":"Temporal increase in Ki-67 index in patients with pancreatic neuroendocrine tumours.","authors":"Pauline Bourdeleau, Johanna Pokossy-Epée, Olivia Hentic, Matthieu Tihy, Zaima Afzal Awan, Anne Couvelard, Maxime Ronot, Vinciane Rebours, Philippe Ruszniewski, Jérôme Cros, Louis de Mestier","doi":"10.1530/ERC-24-0321","DOIUrl":"10.1530/ERC-24-0321","url":null,"abstract":"<p><p>Pancreatic neuroendocrine tumours (PanNETs) have intra-tumour heterogeneity, notably regarding the Ki-67 index, which is a major prognostic factor. The temporal evolution of PanNET biology is poorly known. We aimed to study the prognostic impact of the temporal evolution of Ki-67 and other molecular markers (MEN1, ATRX/DAXX and PDX1/ARX) in PanNETs. We retrospectively studied 109 patients with sporadic PanNETs and serial tumour samples (n = 286), in which we measured the Ki-67 index and the expression of the other markers. Variables associated with shorter overall survival (OS) and Ki-67 increase over time were explored using multivariable analyses. The median time between the initial and last samples was 49.4 months, with a median variation in Ki-67 of +4% (interquartile range (IQR): -1 to +15%; P < 0.001) and +0.5%/year (IQR: -0.2 to +3.3%). Tumour grade increased in 36% of cases. At multivariable analysis, an increase in Ki-67 ≥ 2%/year was associated with shorter OS (HR 1.96, 95% CI [1.02-3.73], P = 0.041). This variation was more common in patients who received alkylating agents (OR 4.47, 95% CI [1.48-15.38], P = 0.011) and was less common in those who achieved tumour control with somatostatin analogues (OR 0.27, 95% CI [0.08-0.82], P = 0.027). MEN1 and ATRX/DAXX expressions were stable over time, while the proportion of alpha-like signatures (PDX1-/ARX+) decreased (P = 0.016); none was associated with Ki-67 nor influenced prognosis. Overall, an increase in PanNET grade and Ki-67 index is frequent over time, indicates a poorer prognosis and is promoted by alkylating agents. Rebiopsy during PanNET evolution seems relevant to adjust prognosis evaluation and therapeutic strategy.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142973994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RET signalling in the pituitary: a double-edged sword for differentiation, apoptosis and therapeutic strategies in acromegaly.","authors":"Miguel Chenlo, Ignacio Bernabeu, Márta Korbonits, Clara V Alvarez","doi":"10.1530/ERC-24-0156","DOIUrl":"10.1530/ERC-24-0156","url":null,"abstract":"<p><p>The discovery of RET mutations in multiple endocrine neoplasia type 2A (MEN2A) in 1993 ignited a revolution in our understanding of this versatile receptor. Since then, the influence of RET has expanded to encompass diverse organs, including the pituitary gland. This review explores the multifaceted role of RET in somatotrophs, focusing on two opposing pathways: proliferation versus differentiation and apoptosis. The binding of glial-derived neurotrophic factor (GDNF) to RET promotes pituitary cell survival and inhibits PIT1-dependent differentiation, while low levels of GDNF trigger differentiation via PIT1. Excessive PIT1, on the other hand, will lead to apoptosis through caspase-3 activation involving the adaptor protein AIP and CDKN2A-ARF/p53. Pathogenic mutations in AIP can disrupt this apoptotic pathway, contributing to somatotrophinoma or prolactinoma development. In this concise review, we highlight the potential of CDKN2A-ARF expression as a prognostic marker for therapy response and discuss the promise of novel RET tyrosine kinase inhibitors for aggressive somatotrophinomas.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142916726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Persistent pre-exhausted CD8+ T cells shape the tumor immune microenvironment in anaplastic thyroid cancer.","authors":"Xianhui Ruan, Mei Tao, Yuanxing Dong, Linfei Hu, Guangwei Xu, Chuanxiang Hu, Yue Huang, Yuqi Wang, Jialong Yu, Wei Luo, Ming Gao, Min Zhao, Xiangqian Zheng","doi":"10.1530/ERC-24-0169","DOIUrl":"10.1530/ERC-24-0169","url":null,"abstract":"<p><strong>Abstract: </strong>Anaplastic thyroid cancer (ATC) is an aggressive form of cancer with poor prognosis, heavily influenced by its tumor immune microenvironment (TIME). Understanding the cellular and gene expression dynamics within the TIME is crucial for developing targeted therapies. This study analyzes the immune microenvironment of ATC and papillary thyroid cancer (PTC) using single-cell RNA sequencing (scRNA-seq). We performed a comprehensive scRNA-seq analysis on ATC and PTC samples, incorporating cell type annotation, marker gene identification and clustering based on gene expression. A specific focus was on the prevalence and biomarkers of pre-exhausted CD8+ T cells in ATC, utilizing the single-cell tumor immune atlas for immune cell characterization. The scRNA-seq analysis identified distinct immune cell populations and differentially expressed genes in ATC and PTC samples. Notably, pre-exhausted CD8+ T cells were found to be prevalent in ATC datasets. Additional immunofluorescence staining and coculture experiments with the ATC cell line identified GNLY, a member of the saposin-like protein family, as a potential biomarker for pre-exhausted CD8+ T cells in ATC. This study provides valuable insights into the immune landscape of ATC, emphasizing the prevalence of pre-exhausted CD8+ T cells and identifying GNLY as a potential biomarker. Understanding the TIME composition and the role of specific immune cells in cancer progression can inform the development of targeted immunotherapies for ATC. Future research should explore the functional implications of GNLY and other identified biomarkers in modulating the immune response in thyroid cancer.</p><p><strong>Highlights: </strong>A computational pipeline was constructed to identify ATC-specific immune cell populations and differentially expressed genes via multiple independent ATC and PTC single-cell transcriptomes.A total of 221 uniquely differentially expressed genes associated with the adaptive immune response across two ATC datasets were identified.Markedly prevalent pre-exhausted CD8+ T cells in ATC datasets compared with PTC datasets were identified.One hundred fifteen potential biomarker genes of pre-exhausted CD8+ T cells were identified, with GNLY experimentally validated as the top candidate.</p>","PeriodicalId":93989,"journal":{"name":"Endocrine-related cancer","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}