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Published on: June 23, 2022
Longitudinal Monitoring of T cell Dynamics in Metastatic Breast Cancer via a Remote Diagnostic Implant
Ian A Schrack1, Rebecca S Pereles1, Brian C Ross1
1Department of Biomedical Engineering, University of Michigan, Ann Arbor; MI, 48109, USA.
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.
Insights
Regulatory T cells decrease in metastatic triple-negative breast cancer, while CD8+ T cells become more active. A synthetic niche helps monitor these T cell changes for better patient stratification.
Area of Science:
- Oncology
- Immunology
- Biomaterials Science
Background:
- Metastatic triple-negative breast cancer (mTNBC) presents significant therapeutic challenges.
- Immunotherapies rely on T cell phenotypes, which change during disease progression.
- Understanding T cell dynamics is crucial for developing effective treatments.
Purpose of the Study:
- To investigate T cell phenotype and function dynamics in metastatic disease.
- To compare T cell responses at the metastatic lung site and a synthetic niche (biomaterial implant).
- To assess the utility of the scaffold as a platform for longitudinal monitoring.
Main Methods:
- Longitudinal analysis of T cell phenotypes (Regulatory T cells, Th1, Th17, CD8+ T cells) in mice with mTNBC.
- Comparison of T cell populations in lung metastasis, scaffold implant, and blood.
- Functional assays to determine T cell suppressive mechanisms (activation, migration).
Main Results:
- Regulatory T cells were reduced at both lung and scaffold sites post-metastasis.
- CD8+ T cells shifted from naive/central memory to effector memory phenotypes.
- Reduced T cell migration, not activation, was the primary suppressive mechanism identified.
- Blood T cell dynamics partially reflected tissue changes but lacked functional correlation.
Conclusions:
- The biomaterial scaffold mimics lung metastatic niches for T cell analysis.
- Longitudinal monitoring via scaffold can reveal disease-related T cell dynamics.
- This approach may aid in stratifying patient populations for immunotherapy.
