Heterogeneity of Dendritic Cells and Other Cells of Myeloid and Lymphoid Origin in Colon and Non-small Cell Lung Cancer
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 64
- 试验地点
- 2
- 主要终点
- Single cell bioinformatics analysis RNA-seq
研究概览
简要总结
Prospective study with the use of biological samples. The centers involved are the Thoracic Surgery and Surgery 1 Units of the San Gerardo Hospital in Monza.
详细描述
BACKGROUND The activation of adaptive immune responses depends on dendritic cells (DCs) and macrophages, myeloid cells of the innate immune system specialized in antigen presentation and in the activation of T cells. This peculiarity of myeloid cells is fundamental not only during diseases infectious but also in the context of cancer, as phagocytes pick up antigens associated with cancer cells and present them to T cells within the tumor microenvironment or in tumor-draining lymph nodes to obtain antitumor responses.
In particular, a positive correlation was observed between the overall tumor content of DC and the survival of cancer patients with different tumors, as well as a better reactivity to therapies based on the use of immunocheckpoint inhibitors (ICB).
The presence of different dendritic cell subtypes has recently been revealed, as well as a specific adaptation of each subtype to the tumor environment.
This is a critical point since the functional heterogeneity of DCs, macrophages and T cells in the tumor microenvironment is probably one of the factors responsible for the success or failure of anticancer immunotherapies. ICB-based therapies have revolutionized the treatment of patients with cancers, such as melanoma and lung cancer, but are currently only beneficial to a minority of patients. Improving understanding of the tumor immune microenvironment is the key to predicting clinical responses to existing therapies and possibly the development of new immunotherapies.
RATIONALE Myeloid cells, such as dendritic cells and macrophages infiltrate many different types of tumors and can exert an antitumor function by activating T and NK cells, or they can carry out a pro-tumor activity by producing anti-inflammatory cytokines and inhibitory molecules. The presence within the tumor of several conventional DC subtypes has been associated with a better prognosis while a pro-tumor function has been proposed for unconventional DCs such as CD14 + CD1c + DC. The presence of macrophages has been associated with a protumoral action.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •men and women aged ≥18 years;
- •clinical diagnosis confirmed by common investigations to establish the presence of colon or lung cancer;
- •lesions> 1 cm;
- •legal capacity to give informed consent in accordance with ICH / EU GCP and national / local regulations.
排除标准
- •pregnancy;
- •presumed pregnancy;
- •known coagulation defects;
- •alcohol or drug abuse
结局指标
主要结局
Single cell bioinformatics analysis RNA-seq
时间窗: Until the end of the study (approximately 5 years).
For the analysis of single-cell RNA-seq data we will exploit the most recent methodologies provided by both 10x Genomics and custom R / Python scripts to perform the identification and characterization of cell subsets.
Single cell RNA-seq library preparation and sequencing.
时间窗: Until the end of the study (approximately 5 years).
10,000 cells for each sample will be loaded on an instrument called Chromium 10X (10x genomics).
次要结局
- Correlation between subtypes of myeloid cells present in the tumor microenvironment and survival(Until the end of the study (approximately 5 years).)
- Spatial distributions of DC subtypes in the tumor microenvironment(Until the end of the study (approximately 5 years).)