PathobiologyPub Date : 2025-07-26DOI: 10.1159/000547335
Julia A M Riggi, Ibrahim Kassem, Christine Galant, Carolien H M Van Deurzen, Martine Berlière, Mieke R Van Bockstal
{"title":"Predictive histopathological markers for upstaging to invasive carcinoma after a biopsy diagnosis of ductal carcinoma in situ (DCIS) of the breast: a hypothesis-generating systematic review.","authors":"Julia A M Riggi, Ibrahim Kassem, Christine Galant, Carolien H M Van Deurzen, Martine Berlière, Mieke R Van Bockstal","doi":"10.1159/000547335","DOIUrl":"https://doi.org/10.1159/000547335","url":null,"abstract":"<p><p>Introduction Around 25% of patients with a biopsy diagnosis of pure ductal carcinoma in situ (DCIS) will be upstaged to invasive breast carcinoma (IBC) after surgery. Because of this upstaging risk, patients with high grade DCIS frequently undergo a sentinel lymph node procedure (SLNP), which can cause surgery-induced morbidity. Presentation with a palpable mass increases the upstaging risk, but histopathological predictors are currently unclear. This PROSPERO-registered systematic review aims to identify which biopsy-based histopathological markers can predict the presence of IBC in the subsequent resection. These results might help to reserve SLNPs for selected high-risk patients, aiming to personalize treatment. Methods PubMed, Embase and Scopus were searched for content using predefined search queries. Three reviewers independently screened the literature in Rayyan by applying predefined criteria. Studies including DCIS with micro-invasion were excluded. Results This review comprised 36 studies, of which 33 were retrospective, representing 18475 patients. The median cohort size was 267 patients (range: 67-3780). The median upstaging risk was 26% (range: 8-52%). The reports studied twenty-three histopathological and immunohistochemical features. Only seven features were investigated in multiple studies, all yielding contradictory results. For instance, thirty-three studies investigated nuclear grade, but only 18 reports demonstrated a significant association with upstaging, independent from cohort size. Conclusion No robust histopathological features can be recommended at present to reliably predict the upstaging risk to IBC after biopsy-diagnosed pure DCIS. We discuss several hypotheses, aiming to explain these contradictory data. Ideally, large-scale multicentre prospective studies should be organised to answer this unmet clinical need.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-22"},"PeriodicalIF":2.0,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathobiologyPub Date : 2025-07-26DOI: 10.1159/000547655
Miguel Bernardo Alves, Nuno Tiago Tavares, Fernanda Fernandes-Pontes, Alexandra Lapa, Rita Guimarães, Paula Lopes, Isaac Braga, Joaquina Maurício, Carmen Jerónimo, Rui Henrique, João Lobo
{"title":"Expression of ENPP1 in testicular germ cell tumors: exploring its role in the pathobiology of distinct histotypes and in prognosis.","authors":"Miguel Bernardo Alves, Nuno Tiago Tavares, Fernanda Fernandes-Pontes, Alexandra Lapa, Rita Guimarães, Paula Lopes, Isaac Braga, Joaquina Maurício, Carmen Jerónimo, Rui Henrique, João Lobo","doi":"10.1159/000547655","DOIUrl":"https://doi.org/10.1159/000547655","url":null,"abstract":"<p><strong>Introduction: </strong>Testicular germ cell tumors (TGCTs) are the most common solid malignancies among young men. Despite good response to cisplatin-based chemotherapy, side effects negatively affect quality of life. Recent development of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) inhibitors opens opportunity for targeted therapy, but ENPP1 expression in TGCTs has not been characterized. We aimed to assess ENPP1 immunoexpression in a cohort of primary and metastatic TGCTs, and in normal testicular parenchyma, looking into differential immunoexpression patterns among subtypes and clinicopathological correlations.</p><p><strong>Methods: </strong>Overall, 90 TGCT individual tumor components from 63 patients diagnosed and treated at a comprehensive cancer center were assessed, using immunohistochemistry to ascertain biomarker expression (combined score of stained tumor cells percentage and intensity). In silico analysis of The Cancer Genome Atlas (TCGA) and Human Protein Atlas (HPA) datasets was performed for additional validation.</p><p><strong>Results: </strong>Significant differences in ENPP1expression across TGCT subtypes were disclosed. Seminomas and embryonal carcinomas showed significantly higher ENPP1 expression compared to other subtypes, the highest levels being found in embryonal carcinoma, which was confirmed with in silico analysis of TCGA and HPA. Expression in metastatic samples was overall lower compared to primary TGCTs. ENPP1 was not expressed in germ cells of healthy testicular parenchyma.</p><p><strong>Conclusion: </strong>We demonstrate that ENPP1 is expressed in TGCTs, mostly embryonal carcinoma (a frequently aggressive tumor subtype), followed by seminoma (the most common TGCT subtype), suggesting potential responsiveness to novel ENPP1 inhibitors. Absent expression in germ cells of healthy testicular parenchyma suggest cancer cells specificity and low probability of fertility-related toxicity.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-19"},"PeriodicalIF":2.0,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Increased infiltration of tissue-resident memory T cells predicts a good response to anti-PD-L1 immunotherapy in extrahepatic cholangiocarcinoma.","authors":"Yoshiyuki Tagayasu, Rin Yamada, Kosuke Kanemitsu, Yoshihiko Kondo, Yukio Fujiwara, Takumi Tanizaki, Rumi Itoyama, Yuki Kitano, Hiromitsu Hayashi, Yoshihiro Komohara, Masaaki Iwatsuki","doi":"10.1159/000547222","DOIUrl":"https://doi.org/10.1159/000547222","url":null,"abstract":"<p><strong>Background: </strong>Extrahepatic cholangiocarcinoma (eCCA) is an aggressive malignancy with a poor prognosis. Immune checkpoint inhibitors (ICIs) targeting PD-L1 enhance antitumor immunity, but reliable predictive biomarkers remain unclear. This study investigated tumor-infiltrating immune cells, including T cells and macrophages, as potential biomarkers for ICI efficacy in eCCA.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 15 eCCA patients who received durvalumab for recurrent or unresectable disease after surgery. Immunohistochemical staining assessed PD-L1, HLA class I/II, CD8, and CD103 expression in resected tumor specimens. ICI response was evaluated using RECIST 1.1 criteria and classified as partial response (PR), stable disease (SD), or progressive disease (PD). Correlations between immune cell infiltration and clinical outcomes were analyzed.</p><p><strong>Results: </strong>Five patients achieved PR, five SD, and five PD. CD8+ and CD103+ T cell infiltration within tumor nests was significantly higher in PR and SD groups than in PD (p=0.032, p=0.0147). High HLA class I expression correlated with response, while PD-L1 and HLA class II showed no significant association. Patients with increased CD8+CD103+ T cells demonstrated better disease control.</p><p><strong>Conclusion: </strong>Intratumoral CD8+ and CD103+ T cells may serve as predictive biomarkers for ICI efficacy in eCCA, highlighting tissue-resident immune cells as therapeutic targets.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-15"},"PeriodicalIF":2.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathobiologyPub Date : 2025-07-25DOI: 10.1159/000546745
Omar Bushara, Charles Crepy D'Orleans, Yash Kadakia, Rucha Alur, David DeVaro, Sunil Singhal
{"title":"Mechanistic Underpinnings of Lung Cancer Initiation in Patients With Human Immunodeficiency Virus Infection.","authors":"Omar Bushara, Charles Crepy D'Orleans, Yash Kadakia, Rucha Alur, David DeVaro, Sunil Singhal","doi":"10.1159/000546745","DOIUrl":"https://doi.org/10.1159/000546745","url":null,"abstract":"<p><p>Lung cancer is the leading cause of cancer related death in the United States. A proven risk factor for the development and progression of lung cancer is human immunodeficiency virus (HIV). HIV persists within the lung in alveolar macrophages and bronchial epithelial cells, reducing mucociliary function and decreasing epithelial integrity. This persistence yields chronic inflammation by way of matrix metalloproteinases, which causes pulmonary injury. Over time, this progresses to pulmonary disease and allows for the development of superimposed pulmonary infections and chronic inflammatory states. This injury is a risk factor for the development of dysplasia, and chronic pulmonary disease and infections further increase the risk for developing lung cancer. HIV persistence and chronic inflammation also lead to CD8+ T cell exhaustion and alterations to macrophages and dendritic cells that blunt the physiologic anti-tumor response. As such, HIV infection promotes initial dysplasia and allows for progression on pre-invasive lesions to frank malignancy. The purpose of this review is to highlight this under-appreciated risk factor and summarize the biologic and immunologic role of HIV in lung cancer initiation and progression. Further research regarding risk reduction and surveillance in this population and the potential increased role of immunotherapy is warranted.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-21"},"PeriodicalIF":2.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Future of Diabetes Care: Exploring the Potential of Bioartificial Pancreas and Do-It-Yourself Artificial Pancreas System Innovations.","authors":"Aagash Nedunchezhian, Archana Rajavel, Ramya Lakshmi Rajendran, Prakash Gangadaran, Raja Natesan Sella","doi":"10.1159/000546926","DOIUrl":"10.1159/000546926","url":null,"abstract":"<p><strong>Background: </strong>Type 1 diabetes mellitus (T1D) is an autoimmune disease marked by the destruction of pancreatic β cells, necessitating lifelong management. Current therapies, such as insulin injections and pancreas transplants, are effective but impose significant burdens, driving the need for innovative solutions. Among these, the bioartificial pancreas (BAP) stands out as a promising approach. By integrating living insulin-producing cells with synthetic matrices, BAP technology aims to replicate natural pancreatic function, offering the potential for more physiologically relevant and patient-friendly treatment.</p><p><strong>Summary: </strong>This review highlights recent advancements in BAP technology, emphasizing innovations in design, materials, and encapsulation techniques that enhance cell viability and function. Key developments include the use of biocompatible materials for cell encapsulation, continuous glucose monitoring systems, and closed-loop control algorithms, which collectively enable real-time glucose regulation. These breakthroughs address critical challenges such as immune rejection and suboptimal device performance, paving the way for clinical translation.</p><p><strong>Key messages: </strong>BAP technology represents a paradigm shift in T1D treatment, with the potential to alleviate the daily burdens of insulin management. However, challenges remain, including improving device longevity, bolstering immune protection, and reducing production costs to ensure broader accessibility. Future advancements may emerge from integrating BAP systems with cell-protective therapies, further enhancing their efficacy. While hurdles persist, the BAP signifies a transformative step toward simplifying diabetes management and improving the quality of life for millions worldwide.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-16"},"PeriodicalIF":3.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathobiologyPub Date : 2025-06-08DOI: 10.1159/000546669
Neha Seth, Phyu Thin Naing, Ram Singh, Saroja Geetha, Kalpana Reddy, Xinmin Zhang, Tianyu Yang, Jessica Caro, Wayne Tam
{"title":"Transdifferentiation of Multiple Myeloma into Histiocytic Sarcoma: Case Report of a Highly Unusual Phenomenon.","authors":"Neha Seth, Phyu Thin Naing, Ram Singh, Saroja Geetha, Kalpana Reddy, Xinmin Zhang, Tianyu Yang, Jessica Caro, Wayne Tam","doi":"10.1159/000546669","DOIUrl":"10.1159/000546669","url":null,"abstract":"<p><strong>Introduction: </strong>Transdifferentiation of multiple myeloma (MM) into histiocytic sarcoma (HS) is exceptionally rare. We report a unique case, confirming this phenomenon through cytogenetics and molecular analyses.</p><p><strong>Case presentation: </strong>A 46-year-old woman with high-risk light chain MM developed extramedullary disease despite multiple lines of therapy. Biopsies revealed atypical histiocytic proliferation consistent with HS. Shared immunoglobulin gene rearrangements, cytogenetic alterations, and gene mutations, including a rare BRAF L485F, confirmed clonal relatedness between the two neoplasms. IGH::MAF translocation specific to MM and IGVH somatic hypermutation in HS suggests divergent evolution from a putative germinal center B-cell (GCB) precursor.</p><p><strong>Conclusions: </strong>This case highlights lineage plasticity of MM to undergo HS transdifferentiation, potentially mediated through a mutated common GCB precursor antecedent to the plasma cell stage, and the subsequent development of HS and MM through acquisition of additional genetic events. Recognition of this exceptional phenomenon and understanding its underlying mechanism have implications for diagnosis, classification, and personalized treatment.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-11"},"PeriodicalIF":3.5,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12270463/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathobiologyPub Date : 2025-05-28DOI: 10.1159/000546206
Szintia Almási, Tibor Krenács, László Krenács, Gábor Cserni
{"title":"Galectin-1 Expression in Breast Cancer Stroma: Prognostic Value in Triple-Negative Breast Cancer.","authors":"Szintia Almási, Tibor Krenács, László Krenács, Gábor Cserni","doi":"10.1159/000546206","DOIUrl":"10.1159/000546206","url":null,"abstract":"<p><strong>Introduction: </strong>Galectin-1 is a lectin with immunosuppressive effect in different solid tumors. We investigated galectin-1 expression in triple-negative breast cancer (TNBC) to determine its prognostic value.</p><p><strong>Methods: </strong>We examined 95 TNBC surgical samples in tissue microarrays with galectin-1 immunohistochemistry (intensity and percentage of staining) and looked for influences on overall and progression-free survivals (PFSs) with the help of Kaplan-Meier estimates. Univariable and multivariable Cox regressions were also analyzed.</p><p><strong>Results: </strong>According to Kaplan-Meier curves, a significantly worse overall survival (OS) was found for TNBC patients showing intense or ≥50% galectin-1 stromal interface staining versus those lacking it. Cox regression analyses suggested that galectin-1 expression was an independent prognosticator in TNBC. According to the quantity of stromal tumor-infiltrating lymphocytes (sTILs), significant survival differences depending on galectin-1 status were only seen in the low sTILs (<30%) subset. Multivariable analysis suggested that galectin-1 expression was an independent prognosticator for PFS.</p><p><strong>Discussion: </strong>The immunosuppressive effects of galectin-1 forming a shield around tumor nests may form an immune escape mechanism and can explain the worse OS and PFS we found in TNBC. Owing to the exploratory nature of the study, the results need confirmation in order to investigate the potentials of anti-galectin-1 therapies.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-10"},"PeriodicalIF":3.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathobiologyPub Date : 2025-05-28DOI: 10.1159/000546139
Ádám Ferenczi, Sofia Germano, Joana Afonso, Levente Kuthi, Tamás Lantos, Anita Sejben
{"title":"Duodenal Foveolar Adenoma: Case Presentation with Whole Exome Sequencing and Review of the Literature.","authors":"Ádám Ferenczi, Sofia Germano, Joana Afonso, Levente Kuthi, Tamás Lantos, Anita Sejben","doi":"10.1159/000546139","DOIUrl":"10.1159/000546139","url":null,"abstract":"<p><strong>Introduction: </strong>Duodenal adenomas are most commonly associated with polyposis syndromes. Foveolar adenoma is an especially rare entity with an unknown aetiology. We present a case of duodenal foveolar adenoma with coexisting metaplasia, whole exome sequencing results, and the first literature review.</p><p><strong>Case presentation: </strong>Hereby, we present the case of a 58-year-old man, whose polypectomy specimen revealed a lesion composed of mainly foveolar cells with low-grade dysplasia and was concluded as foveolar adenoma. Due to the incomplete resection, polypectomy was repeated; this time, foveolar adenoma was diagnosed with high-grade dysplasia. Foveolar differentiation was proved with MUC5AC immunohistochemistry; in addition, KRAS and SMAD4 pathogenic mutations were identified.</p><p><strong>Discussion: </strong>Duodenal foveolar adenoma remains a controversial and an enigmatic entity. Our paper presents such a lesion with first low-grade, then high-grade dysplasia, and KRAS mutation, identical to gastric manifestations. The further sample of our patient suggests foveolar metaplasia as an aetiological factor that supports the literature data.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-6"},"PeriodicalIF":3.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12187099/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144174482","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Improved Diagnosis of Glioblastoma, IDH-Wildtype, Metastasis through Molecular and DNA Methylation Profiling: Two Case Reports.","authors":"Alexandre Bertucci, Elise Kaspi, Marylin Barrie, Laurence Schenone, Amira Amri, Alexandre Astier, Isabelle Nanni, Mario Abaji, Olivier Chinot, Patrice Roll, Emeline Tabouret, Romain Appay, Diane Frankel","doi":"10.1159/000546348","DOIUrl":"10.1159/000546348","url":null,"abstract":"<p><strong>Introduction: </strong>Glioblastoma, the most common primary malignant brain tumor in adults, accounts for approximately 50% of primary malignant brain tumors. Extracranial metastases are extremely rare, affecting <0.5% of patients. This article describes 2 cases where next-generation sequencing and DNA methylation profiling confirmed extracranial metastases of glioblastoma, IDH-WT.</p><p><strong>Case presentation: </strong>The first case involves a 77-year-old man who developed lung and liver mass within months of diagnosis. While both biopsies revealed undifferentiated malignant tumor, identical genetic mutations on the lung biopsy and DNA methylation profiling on the liver biopsy confirmed glioblastoma metastases. The second case details a 75-year-old woman diagnosed with glioblastoma, IDH-WT who presented diffuse bone infiltration. Bone marrow aspirate and bone marrow biopsy associated with NGS and methylation profiling confirmed glioblastoma metastasis. Both patients succumbed within 8 months.</p><p><strong>Conclusion: </strong>These cases underscore the importance of molecular diagnostics in identifying glioblastoma metastases and guiding treatment, particularly in rare presentations involving extracranial spread.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-9"},"PeriodicalIF":3.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
PathobiologyPub Date : 2025-05-16DOI: 10.1159/000545488
Miguel A Idoate, Mikel Ariz-Galilea, Ainhoa Urbiola-Casales, Miriam Alonso-García, Jesús Machuca-Aguado, Carlos Ortiz de Solórzano, Eloy Rivas-Infante, Rainiero Avila-Polo, Michele Biscuola
{"title":"Immune Scenario Identification Combining Multiplexed, Quantitative, and Advanced Imaging Analysis Could Be Relevant in Immunotherapy against Glioblastoma and Grade 4 Astrocytoma.","authors":"Miguel A Idoate, Mikel Ariz-Galilea, Ainhoa Urbiola-Casales, Miriam Alonso-García, Jesús Machuca-Aguado, Carlos Ortiz de Solórzano, Eloy Rivas-Infante, Rainiero Avila-Polo, Michele Biscuola","doi":"10.1159/000545488","DOIUrl":"10.1159/000545488","url":null,"abstract":"<p><strong>Introduction: </strong>In our research on understanding glioblastoma's resistance mechanisms to immunotherapy, we extensively investigated through an innovative technology that enables the simultaneous assessment of multiple biomarkers. With this approach, we aim to gain deeper insights into the interplay between immunosuppressive cells (ICs) and effector cells (ECs).</p><p><strong>Methods: </strong>One hundred twenty-six cases of glioblastoma were studied employing tissue microarrays stained with a panel of immune infiltrate validated via multiplex immunofluorescence and quantified by advanced image analysis. All cases were categorized according to an EC/IC ratio and their respective medians. Statistical correlations between cell populations and with survival were calculated.</p><p><strong>Results: </strong>M2 macrophages were the most abundant ICs, followed by a variable number of ECs and protumoral activated microglia, and a scant quantity of FoxP3 cells. EC showed a statistically significant direct positive correlation with ICs. The patients with tumors exhibiting an EC/IC ratio ≤0.063 displayed a significantly poorer outcome. Furthermore, in the context of incomplete surgical resection, significant differences were evident considering immune scenarios.</p><p><strong>Conclusions: </strong>By integrating multiplex technology with advanced imaging analysis, we successfully identified 4 distinct immune scenarios in glioblastoma. We observed a favorable immune scenario characterized by a relatively high EC/IC ratio, which is especially evident in the clinical setting of incomplete tumor resection. This promising immune scenario holds significant potential for selecting suitable candidates for immunotherapy in glioblastoma.</p>","PeriodicalId":19805,"journal":{"name":"Pathobiology","volume":" ","pages":"1-20"},"PeriodicalIF":3.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}