Longitudinal Monitoring of T cell Dynamics in Metastatic Breast Cancer via a Remote Diagnostic Implant.

Immunomedicine Pub Date : 2024-12-01 Epub Date: 2025-06-09 DOI:10.1002/imed.70000
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
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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.

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。
转移性三阴性乳腺癌由于进展迅速和治疗选择有限,对健康构成重大挑战。针对转移性肿瘤的T细胞应答的免疫疗法依赖于特定T细胞表型的存在,这种表型随着疾病的进展和治疗而动态演变。在此,我们研究了转移性疾病进展过程中的T细胞表型动力学,重点关注肺转移部位和作为合成转移生态位的生物材料植入物,后者为纵向分析提供了一个可接近的非重要组织。与健康小鼠相比,在疾病发生和进展后,肺和支架植入部位转移的调节性T细胞减少,而Th1和Th17群体保持相对稳定。随着疾病进展,CD8+ T细胞从naïve和中枢记忆转变为效应记忆。此外,涉及转移组织的功能分析表明,主要的T细胞抑制机制是减少迁移,对T细胞激活没有影响。基于血液的分析证明了其中一些表型动力学,但并没有概括功能分析。总的来说,支架为动态监测T细胞表型和功能提供了一个平台,类似于转移性肺,能够对疾病进展进行纵向监测,从而对患者群体进行分层。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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