Ian A Schrack, Rebecca S Pereles, Brian C Ross, Jeffrey A Ma, Russell R Urie, Emily R Irish, Guillermo Escalona, Kate V Griffin, Kathryn Kang, Jacqueline S Jeruss, Lonnie D Shea
{"title":"Longitudinal Monitoring of T cell Dynamics in Metastatic Breast Cancer via a Remote Diagnostic Implant.","authors":"Ian A Schrack, Rebecca S Pereles, Brian C Ross, Jeffrey A Ma, Russell R Urie, Emily R Irish, Guillermo Escalona, Kate V Griffin, Kathryn Kang, Jacqueline S Jeruss, Lonnie D Shea","doi":"10.1002/imed.70000","DOIUrl":null,"url":null,"abstract":"<p><p>Metastatic triple negative breast cancer poses a significant health challenge due to rapid progression and limited treatment options. Immunotherapies targeting T cell responses against metastatic tumors depend on the presence of specific T cell phenotypes, which dynamically evolve with disease progression and treatment. Herein, we investigate T cell phenotype dynamics throughout metastatic disease progression, focusing on both the metastatic site in the lung and a biomaterial implant that serves as a synthetic metastatic niche, with the latter providing an accessible, non-vital tissue for longitudinal analysis. Regulatory T cells were reduced at the lung and scaffold implant sites of metastasis following disease onset and progression relative to healthy mice, while Th1 and Th17 populations remained relatively stable. CD8+ T cells transitioned from naïve and central memory to effector memory with disease progression. Additionally, functional analyses involving the metastatic tissues suggested the primary T cell suppressive mechanisms was reduced migration, with no impact on T cell activation. Blood-based analyses demonstrated some of these phenotypic dynamics yet does not recapitulate the functional assays. Collectively, the scaffold provides a platform for dynamically monitoring T cell phenotypes and functions similar to the metastatic lung, enabling longitudinal monitoring of disease progression that could stratify patient populations.</p>","PeriodicalId":73348,"journal":{"name":"Immunomedicine","volume":"4 2","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12382481/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Immunomedicine","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/imed.70000","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/6/9 0:00:00","PubModel":"Epub","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Metastatic triple negative breast cancer poses a significant health challenge due to rapid progression and limited treatment options. Immunotherapies targeting T cell responses against metastatic tumors depend on the presence of specific T cell phenotypes, which dynamically evolve with disease progression and treatment. Herein, we investigate T cell phenotype dynamics throughout metastatic disease progression, focusing on both the metastatic site in the lung and a biomaterial implant that serves as a synthetic metastatic niche, with the latter providing an accessible, non-vital tissue for longitudinal analysis. Regulatory T cells were reduced at the lung and scaffold implant sites of metastasis following disease onset and progression relative to healthy mice, while Th1 and Th17 populations remained relatively stable. CD8+ T cells transitioned from naïve and central memory to effector memory with disease progression. Additionally, functional analyses involving the metastatic tissues suggested the primary T cell suppressive mechanisms was reduced migration, with no impact on T cell activation. Blood-based analyses demonstrated some of these phenotypic dynamics yet does not recapitulate the functional assays. Collectively, the scaffold provides a platform for dynamically monitoring T cell phenotypes and functions similar to the metastatic lung, enabling longitudinal monitoring of disease progression that could stratify patient populations.