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":"通过远程诊断植入物纵向监测转移性乳腺癌的T细胞动力学。","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":"{\"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}","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}
Longitudinal Monitoring of T cell Dynamics in Metastatic Breast Cancer via a Remote Diagnostic Implant.
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.