Cancers最新文献

{"title":"Cytokine Profiling of Children, Adolescents, and Young Adults Newly Diagnosed with Sarcomas Demonstrates the Role of IL-1β in Osteosarcoma Metastasis.","authors":"Laurel Kastner, William Kandalaft, Aakash Mahant Mahant, Jessica Crimella, Sydney Hakim, Xiao P Peng, Michael S Isakoff, Masanori Hayashi, David M Loeb","doi":"10.3390/cancers17183009","DOIUrl":"10.3390/cancers17183009","url":null,"abstract":"<p><p><b>Background:</b> Sarcomas are a heterogeneous group of mesenchymal tumors frequently diagnosed in pediatric and young adult patients. These tumors respond poorly to conventional immunotherapy, although the precise reason for this is not known. We sought to characterize the systemic immune response to sarcomas by measuring the levels of circulating cytokines in the plasma of newly diagnosed sarcoma patients, testing the hypothesis that the nature of a patient's immune response to their tumor directly affects outcome. <b>Methods:</b> Plasma was collected from newly diagnosed, treatment-naive pediatric sarcoma patients participating in an ongoing clinical trial, MCC20320. A panel of 18 cytokines was selected, and cytokine levels were measured using the Luminex platform. Cytokine levels were analyzed based on clinicopathological parameters such as gender, age, stage, and survival. <b>Results:</b> We found that the cytokine profile in patients newly diagnosed with sarcoma is distinct from healthy controls, but different sarcomas were not distinguishable. Patients with osteosarcoma who had elevated levels of multiple cytokines had inferior overall survival compared to those with fewer or no elevated levels. Similarly, elevated levels of individual cytokines and chemokines, including IL-24, CXCL5, and CXCL10, were associated with inferior event-free or overall survival in patients with osteosarcoma. Perhaps most significantly, elevated IL-1β at diagnosis was associated with metastatic presentation and inferior event-free survival in patients with osteosarcoma. <b>Conclusions:</b> These findings suggest that pediatric sarcoma patients mount a systemic immune response that may affect event-free or overall survival. IL-1β in particular may be a valuable therapeutic target for osteosarcoma patients.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DNA Damage and Repair in Ovarian Cancer: Focus on MicroRNAs.","authors":"Katarzyna D Arczewska, Agnieszka Piekiełko-Witkowska","doi":"10.3390/cancers17183011","DOIUrl":"10.3390/cancers17183011","url":null,"abstract":"<p><p>Ovarian cancer (OvCa) is one of the most life-threatening female malignancies that affects 300,000 women annually worldwide. Impaired mechanisms of DNA repair are the leading cause of mutations underlying the OvCa development. microRNAs are short non-coding RNAs that regulate the expression of genes by binding to their transcripts and inducing mRNA degradation or inhibition of translation. Here, we review the miRNA-mediated dysregulation of genes involved in DNA damage response (DDR) and DNA repair pathways in OvCa. Apparently, miRNAs are capable of targeting the crucial mediators of DDR (e.g., miR-203a-3p targeting ATM (Ataxia Telangiectasia Mutated)), homologous repair (such as BRCA1 targeted by miR-9, miR-1255b, miR-193b, and miR-148b), non-homologous end joining (with RNF8 being regulated by miR-214), nucleotide excision repair (involving DDB2 targeted by miR-328-3p), or translesion DNA synthesis (involving RAD18, participating also in homologous repair and targeted by miR-379-5p). We also discuss miRNAs (such as miR-519a-3p, let-7e, miR-216b), which affect responses to OvCa therapy by targeting PARP1 (Poly(ADP-Ribose) Polymerase-1). Finally, we also discuss why, despite the identification of multiple miRNAs capable of regulating DNA repair genes, as well as those involved in the response to therapy, no miRNA-based drugs have been approved for OvCa treatment in clinics.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12469197/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective Evaluation of Cervical Scrapings CDO1 and CELF4 Methylation (epiHERA^®) Assay in Detection of Endometrial Cancer.","authors":"Ho-Sze Jacqueline Lee, Shiye Wu, Suet-Ying Yeung, Chun-Wai Cheung, Wen-Ying Linda Fung, Pui-Kei Sonia Kwok, Kar-Kei Yung, Tsz-Kei Sani Wong, Abhiram Kanneganti, Tat-San Lau","doi":"10.3390/cancers17183010","DOIUrl":"10.3390/cancers17183010","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Our study evaluates the performance of the CDO1 and CELF4 methylation assay of cervical scrapings in diagnosing endometrial cancer. <b>Methods</b>: Patients referred for abnormal uterine bleeding, suspected endometrial pathology on imaging, endometrial hyperplasia, or cancer, who were indicated for endometrial sampling +/- hysteroscopy +/- hysterectomy, were recruited prospectively from the gynecology clinic of Prince of Wales Hospital, Hong Kong, from January 2023 to November 2024. Methylation assay was performed on the cervical scrapings of the participants, with the results compared to endometrium histology obtained on the same day. <b>Results</b>: Methylation assay results of 675 patients were compared to 629 outpatient endometrial assessments and 46 hysterectomy histology. The assay yields an accuracy of 97.3%, sensitivity of 84.1%, specificity of 98.8%, PPV of 89.2%, and NPV of 98.2%. The AUC is 0.92 with a Kappa coefficient of 0.85. The false-negative rate was 0.8% among the 629 endometrial assessment cases. Endometrial thickness, abnormal cervical cytology, and endometrial hyperplasia significantly affected the accuracy. Among seven false-positive cases, five had endometrial hyperplasia and two had cervical intraepithelial neoplasia. Eventually, three patients were diagnosed with endometrial cancer and one with cervical cancer 1 to 4 months later. <b>Conclusions</b>: Methylation assay of cervical scrapings is highly accurate in diagnosing endometrial cancer with a high sensitivity, specificity, and low false-negative rate. It can act as a triage to reduce invasive endometrial assessment. All false-positive cases were related to neoplastic processes in the genital tract, indicating that it may be useful for detecting cancer early, before histological change is evident.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sequencing Choices and Real-World Clinical Management in Advanced Grade 2/3 GEP-NET Treatment: The Emerging Role of PRRT.","authors":"Aman Chauhan, Thorvardur R Halfdanarson, Namrata Vijayvergia","doi":"10.3390/cancers17183008","DOIUrl":"10.3390/cancers17183008","url":null,"abstract":"<p><p>The prognosis of high-grade gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is highly variable and reported median overall survival remains low. There is no established standard of care for patients with higher grade 2 (G2) (Ki-67 ≥ 10% and ≤ 20%) and grade 3 (G3) (Ki-67 ≥ 20% and ≤ 55%) GEP-NETs and most of the current treatment regimens, particularly for G3 NETs, are extrapolated from lower-grade GEP-NET treatments or based on data from small retrospective studies. Robust evidence to support treatment recommendations for high-grade NETs, especially in the first-line (1L) setting, is limited and the optimal treatment sequence has not been clearly defined. This review summarizes the latest literature on sequencing of therapies, identifies patient selection considerations for utilizing peptide receptor radionuclide therapy (PRRT), and offers data-driven expert opinions and clinical practice recommendations in high-grade GEP-NETs. As authors, we recommend that all patients with well-differentiated, higher G2 and G3 NETs are evaluated with [⁶⁸Ga]Ga-DOTA-peptide positron emission tomography (PET) for baseline somatostatin receptor expression and if positive, a 1L treatment option of PRRT should be considered, especially in clinically stable patients. Somatostatin analog therapy may benefit patients with low-volume, indolent disease, and chemotherapy is usually a better fit for patients in visceral crisis, in need of urgent treatment, or with no access to [⁶⁸Ga]Ga-DOTA-peptide PET. In complex cases, a robust discussion at a multidisciplinary NET tumor board can be beneficial.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468650/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173787","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Outcome in Elderly Head and Neck Cancer Patients Treated with Concomitant Cisplatin and Radiotherapy.","authors":"Chiara Lucrezia Deantoni, Andrea Galli, Davide Valsecchi, Luca Porcu, Lucrezia Tranò, Laura Giannini, Italo Dell'Oca, Anna Chiara, Vittorio Gioffrè, Moreno Tresoldi, Nadia Gisella Di Muzio, Leone Giordano, Aurora Mirabile","doi":"10.3390/cancers17183007","DOIUrl":"10.3390/cancers17183007","url":null,"abstract":"<p><strong>Background: </strong>Cisplatin (CDDP) concomitant to radiotherapy (RT) is one of the main treatments for locally advanced head and neck squamocellular carcinoma (LA HNSCC); nevertheless, elderly patients are underrepresented in trials and frequently receive less intensive and suboptimal treatments, which often are unimodal, even if it is well demonstrated how chemoradiotherapy (CRT) with CDDP is superior to RT alone. We aim to analyze clinical feasibility in terms of acute toxicity and treatment adherence in patients receiving concurrent high-dose CDDP and RT with curative or adjuvant intent, comparing elderly (≥65 years) with young (<65 years) patients.</p><p><strong>Methods: </strong>This is a monocentric, observational, prospective study of consecutive LA HNSCC patients treated with high dose CDDP concomitant to RT, from January 2017 to June 2024. The primary aim is to compare the performance of elderly patients with young patients in terms treatment adherence and toxicity, while the secondary aim is to assess treatment efficacy in terms of OS and PFS endpoints. The LA HNSCC patients were selected only by treatment, so all patients who did not receive chemoradiation were excluded. No difference in terms of compliance and toxicity events >G1 in the elderly versus young population is the null hypothesis. Data were analyzed using MedCal statistical software 14.12. A <i>p</i> < 0.05 was considered statistically significant.</p><p><strong>Results: </strong>A total of 170 patients were included in the study, according to the selection criteria stated. Only 7 elderly (12.3%) patients received a dose < 200 mg/m², whereas 163 patients (87.7%) received ≥ 200 mg/m² and all elderly patients completed RT, indicating a high level of adherence and effective management of treatment protocols, in front of a comparable incidence of acute toxicity to young patients (<i>p</i>-value: 0.84). OS and PFS were not statistically different between elderly and young patients (<i>p</i> = 0.20 and <i>p</i> = 0.72, respectively).</p><p><strong>Conclusions: </strong>Our findings suggest the feasibility of curative oncological treatment for elderly individuals with LA HNSCC, if they are well selected and adequately supported. Future studies should focus on validating and expanding these results to improve patient care and outcomes.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Presence of Adipophilin-Positive Cancer-Associated Fibroblasts Is an Independent Poor Prognostic Indicator and Is Correlated with Immature-Type Desmoplastic Reaction in Patients with Colorectal Cancer.","authors":"Toshinori Kobayashi, Mitsuaki Ishida, Hiroki Uehara, Shoichiro I, Norikazu Yamada, Yuto Igarashi, Chie Hagiwara, Yoshihiro Mori, Yoshinobu Hirose, Jun Watanabe","doi":"10.3390/cancers17183006","DOIUrl":"10.3390/cancers17183006","url":null,"abstract":"<p><strong>Background/objectives: </strong>Immature-type (IM type) desmoplastic reaction (DR) is a poor prognostic indicator of CRC; however, the underlying mechanism has not yet been clarified. Recent studies have demonstrated that energy metabolism, including lipid metabolism, in cancer-associated fibroblasts (CAFs) can critically impact cancer cell growth. The prognostic significance of lipid-laden CAFs in CRC has not yet been elucidated. This study aimed to clarify whether the presence of lipid-laden CAFs correlates with the DR type and prognosis in CRC.</p><p><strong>Methods: </strong>We enrolled patients with pT3 or pT4 CRC who underwent surgical resection without neoadjuvant chemoradiotherapy. Immunohistochemical staining for adipophilin (ADP) was performed to determine the presence of lipid-laden CAFs.</p><p><strong>Results: </strong>The cohort included 70 patients (49 men and 21 women) with a median age of 74 years. ADP-positive lipid-laden CAFs were observed in 37 patients (53%). The presence of lipid-laden CAFs and ADP expression in carcinoma cells at the invasive front was significantly correlated with IM-type DR (<i>p</i> < 0.0001 and <i>p</i> = 0.0063, respectively). The presence of lipid-laden CAFs was an independent poor prognostic indicator based on multivariate analysis (hazard ratio: 3.65; 95% confidence interval: 1.082-13.038; <i>p</i> = 0.0368).</p><p><strong>Conclusions: </strong>These results suggest that the presence of lipid-laden CAFs enhance cancer progression, invasion, and metastasis, and that IM-type DR might be related to the lipid-rich tumor microenvironment.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ViT-DCNN: Vision Transformer with Deformable CNN Model for Lung and Colon Cancer Detection.","authors":"Aditya Pal, Hari Mohan Rai, Joon Yoo, Sang-Ryong Lee, Yooheon Park","doi":"10.3390/cancers17183005","DOIUrl":"10.3390/cancers17183005","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Lung and colon cancers remain among the most prevalent and fatal diseases worldwide, and their early detection is a serious challenge. The data used in this study was obtained from the Lung and Colon Cancer Histopathological Images Dataset, which comprises five different classes of image data, namely colon adenocarcinoma, colon normal, lung adenocarcinoma, lung normal, and lung squamous cell carcinoma, split into training (80%), validation (10%), and test (10%) subsets. In this study, we propose the ViT-DCNN (Vision Transformer with Deformable CNN) model, with the aim of improving cancer detection and classification using medical images. <b>Methods:</b> The combination of the ViT's self-attention capabilities with deformable convolutions allows for improved feature extraction, while also enabling the model to learn both holistic contextual information as well as fine-grained localized spatial details. <b>Results:</b> On the test set, the model performed remarkably well, with an accuracy of 94.24%, an F1 score of 94.23%, recall of 94.24%, and precision of 94.37%, confirming its robustness in detecting cancerous tissues. Furthermore, our proposed ViT-DCNN model outperforms several state-of-the-art models, including ResNet-152, EfficientNet-B7, SwinTransformer, DenseNet-201, ConvNext, TransUNet, CNN-LSTM, MobileNetV3, and NASNet-A, across all major performance metrics. <b>Conclusions:</b> By using deep learning and advanced image analysis, this model enhances the efficiency of cancer detection, thus representing a valuable tool for radiologists and clinicians. This study demonstrates that the proposed ViT-DCNN model can reduce diagnostic inaccuracies and improve detection efficiency. Future work will focus on dataset enrichment and enhancing the model's interpretability to evaluate its clinical applicability. This paper demonstrates the promise of artificial-intelligence-driven diagnostic models in transforming lung and colon cancer detection and improving patient diagnosis.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preoperative MRI Predictors for Post-Prostatectomy Urinary Incontinence.","authors":"Franco Alchiede Simonato, Guglielmo Mantica, Martina Beverini, Francesca Ambrosini, Francesco Chierigo, Veronica Giasotto, Nicola Pavan, Alchiede Simonato, Carlo Terrone","doi":"10.3390/cancers17183004","DOIUrl":"10.3390/cancers17183004","url":null,"abstract":"<p><p><b>Background</b>: We investigated the predictive role of prostatic morphology on preoperative multiparametric magnetic resonance imaging for post-prostatectomy urinary incontinence. <b>Methods</b>: Patients who underwent robot-assisted radical prostatectomy between February 2018 and October 2021 and who were not previously incontinent, did not undergo radiotherapy, hormone therapy, or transurethral resection of the prostate, and who had a follow-up longer than 12 months were selected. For each patient, a radiology physician evaluated the preoperative magnetic resonance imaging, measuring prostatic and membranous urethral length, classifying prostatic apex according to the Lee Type, and estimating the presence of the median lobe and its intravesical protrusion. Multivariate logistic regression models evaluated the influence of anatomic features measured in magnetic resonance imaging on urinary continence recovery, defined as daily pad usage less than or equal to one, considering age, body mass index, prostate volume, International Prostatic Symptoms Score, the usage of a nerve sparing technique, and the International Society of Urological Pathology classification. <b>Results</b>: A total of 95 patients who underwent robot-assisted radical prostatectomy were enrolled. Median age, median body mass index, and median PSA density were respectively 66 years (62, 70), 26.12 kg/m² (23.88, 28.09), and 0.16 ng/mL/cc (0.10, 0.26). Patients with urinary continence ranged from 32 (33.7%) at baseline to 93 (97.8%) after one year from surgery. At preoperative magnetic resonance, Lee Type was almost equally distributed, but Type C was less represented (18 patients, 18.9%) and Type D was more frequent (31 patients, 32.2%). Median prostatic urethral length, median membranous urethral length, and median intravesical prostatic protrusion were respectively 36 mm (31, 42), 15 mm (13, 16), and 0 mm (0, 0). Multivariate logistic regression models showed no statistical significance, except for Lee Type C and A comparison at vesical catheter removal after surgery (OR 0.17; 95% CI 0.04-0.71; <i>p</i>-value 0.01). <b>Conclusions</b>: The results of this study showed that patients who had Lee Type C might have higher probability of early urinary continence recovery, but no further statistically significant correlations were found.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Cost of Breast Cancer: Economic and Social Perspective.","authors":"Izabela Gąska, Aleksandra Czerw, Monika Pajewska, Olga Partyka, Andrzej Deptała, Anna Badowska-Kozakiewicz, Michał Budzik, Katarzyna Sygit, Paulina Wojtyła-Buciora, Jarosław Drobnik, Piotr Pobrotyn, Dorota Waśko-Czopnik, Julia Pobrotyn, Ewa Bandurska, Weronika Ciećko, Elżbieta Grochans, Anna M Cybulska, Daria Schneider-Matyka, Kamila Rachubińska, Petre Iltchev, Tomasz Czapla, Remigiusz Kozlowski","doi":"10.3390/cancers17183012","DOIUrl":"10.3390/cancers17183012","url":null,"abstract":"<p><p>Breast cancer is the most common malignant cancer among women, following lung cancer in the general population [...].</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic Insights into Proglumide's Role in Immune Cell Efficacy and Response to Immune Checkpoint Inhibitor Therapy in Hepatocellular Carcinoma.","authors":"Priyanka S Doneparthi, Hong Cao, Wenqiang Chen, Wenyu Dou, Hong-Bin Fang, Jill P Smith","doi":"10.3390/cancers17182998","DOIUrl":"10.3390/cancers17182998","url":null,"abstract":"<p><strong>Background: </strong>New strategies are needed to improve the response to immune checkpoint inhibitors for the treatment of hepatocellular carcinoma.</p><p><strong>Methods: </strong>Mice bearing HCC tumors were treated with PBS (control), a PD-1 antibody (PD-1Ab), proglumide, or the combination of proglumide and the PD-1Ab. The tumor microenvironment (TME) was evaluated histologically for fibrosis and by immunohistochemistry for immune cells. To investigate the mechanisms involved in T-cell efficiency, mouse spleen cells were isolated and examined for T-cell exhaustion markers and cytokine release. The mouse microbiome was analyzed using whole-genome sequencing before therapy and at the end of the study.</p><p><strong>Results: </strong>The combination of proglumide with a PD-1Ab decreased tumoral fibrosis better than monotherapy, and altered the immune cell signature in the TME by decreasing M2-polarized macrophages and increasing the influx of CD8+ T-cells. Proglumide monotherapy or in combination with the PD-1Ab decreased T-cell exhaustion markers and improved cytokine release. The combination therapy resulted in changes to the microbiome, including increased beneficial bacteria and genera known to enhance the efficacy of ICIs.</p><p><strong>Conclusions: </strong>Co-administration of proglumide with ICIs resulted in remodeling of the TME, changing a \"cold\" tumor to a \"hot\" immune-responsive tumor, activating T-cells, and altering the host microbiome to a population of bacteria that are beneficial.</p>","PeriodicalId":9681,"journal":{"name":"Cancers","volume":"17 18","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12468770/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145173905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}