Longitudinal monitoring of T cell dynamics in metastatic breast cancer via a remote diagnostic implant

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 dise...

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Main 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 Ph.D.
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:ImmunoMedicine
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Online Access:https://doi.org/10.1002/imed.70000
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Summary: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 mechanism was reduced migration, with no impact on T cell activation. Blood‐based analyses demonstrated some of these phenotypic dynamics yet do 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.
ISSN:2510-5345