Age-related Changes in the Immune System and Their Impact on Elderly Breast Cancer
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- - Are there differences in tumor stroma, both with regard to immune infiltration and cellular senescence, between young and old patients, and between old fit and old frail patients?
研究概览
简要总结
This research project aims to study this intriguing relationship between ageing and breast cancer biology, and more specifically the changes that occur within the tumor microenvironment with increasing age. Furthermore, it will focus on the link between these microenvironmental changes and organismal ageing (as measured by chronological age, geriatric evaluation of elderly patients, and circulating biomarkers of ageing), since it seems logical that age-related changes in the stromal part of a tumor (fibroblasts, immune cells, endothelial cells, fatty cells, ...i.e. host cells) are due to the ageing process of the entire body. Most particularly, the amount and type of infiltrating immune cells might reflect the degree of immunosenescence of the host. More and more research points out the crucial role of the immune system in tumorigenesis and progression, and, at the same time, the immune system is one of the most affected components in the process of ageing. .
详细描述
Despite the high relevance of ageing/immunosenescence and frailty in oncogeriatric practice, immuno-senescence markers have so far not been considered in concert with clinical tumor characteristics and the profile of tumor infiltrating leukocytes. In the proposed project, the investigators will examine immunosenescence markers in blood and characterize the leukocyte infiltrate in the tumor microenvironment in the setting of elderly breast cancer.
The main goal of this project is thus to investigate the relation and interaction between the following 3 aspects:
(i) immune status of the host: chronological age and immunosenescence in peripheral blood; (ii) tumor microenvironment: local immune response (evaluated via assessment of the amount and nature of tumor infiltrating leukocytes [TIL]); (iii) clinical tumor characteristics: tumor size, grade, receptor status, lymph node involvement.
To realize this project, the investigators will set up a prospective clinical study comprising three distinct age categories of breast cancer patients and integrating a variety of immunosenescence markers. Different specific manifestations of immune system ageing will be studied : age-related pro-inflammatory status (inflammageing), increased expression of the senescence marker p16INK4a in T lymphocytes, shifts in subset composition of the PBMC pool, age-associated changes in expression of immune-related genes in PBMC and altered abundance of specific ageing-related plasma microRNAs.
At the tumor microenvironmental level, the leukocyte infiltrate will be studied in detail. The profile of tumor-infiltrating immune cells will be compared between the distinct age groups and will be correlated to systemic markers of ageing/immunosenescence (in blood) and tumor biology, most particularly lymph node involvement.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 35 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •o Patients newly diagnosed with breast cancer who will undergo surgery and gave written informed consent
- •Group 1 : 30 patients aged 70+ Group 2 : 15 patients aged 55-65 (post-menopausal) Group 3 : 15 patients aged 35-45 (pre-menopausal)
- •Tumor selection : grade II/III invasive tumor, any histological type, ER-positive, HER2-negative
- •Tumor size ≥1.5 cm (clinical assessment: mammoechography and/or clinical examination)
排除标准
- 未提供
结局指标
主要结局
- Are there differences in tumor stroma, both with regard to immune infiltration and cellular senescence, between young and old patients, and between old fit and old frail patients?
时间窗: at diagnosis
次要结局
- - Does the local immune response in the tumor (amount and type of infiltrating cells) correlate with subset profile of circulating immune cells (PBMC) and immunosenescence markers in the plasma, and with clinical ageing?(at diagnosis)
- - Is there a relation between senescence markers expressed in tumor stroma (SAβ-galactosidase, heterochromatinisation, SASP) and ageing markers measured in the blood?(at diagnosis)
- - Do immune infiltration of the tumor, stromal senescence in the tumor and plasma ageing/immunosenescence profile correlate with relapse and survival (long term outcome)?(at diagnosis)
研究者
prof. dr. Hans Wildiers
adjunct head of clinic
Universitaire Ziekenhuizen KU Leuven