Mechanistic Study of Histidine-mediated Regulation of Antigen Presentation in Colorectal Cancer to Enhance Sensitivity to Immunotherapy
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 150
- 主要终点
- SLC15A3 expression
研究概览
简要总结
This observational study aims to investigate the role of histidine and its transporter SLC15A3 in modulating the sensitivity of colorectal cancer to immunotherapy. By analyzing the expression of SLC15A3 in tumor/normal colonic tissues from patients with colorectal cancer and assessing serum histidine metabolic levels, the study seeks to identify potential targets associated with therapeutic resistance and explore possible intervention strategies to improve immune checkpoint blockade treatment efficacy.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Retrospective
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
- •Participants aged ≥18 years and ≤100 years.
- •Patients pathologically diagnosed with colorectal cancer based on colonoscopy or surgical specimens and biopsy examination; or patients who previously received PD-1 monoclonal antibody immunotherapy for colorectal cancer.
排除标准
- •Age <18 years.
- •Presence of poorly controlled metabolic diseases, including hypertension, diabetes mellitus, hyperlipidemia, hyperuricemia, or hyperthyroidism.
- •Presence of other severe gastrointestinal diseases, including inflammatory bowel disease, ischemic bowel disease, familial adenomatous polyposis, liver cirrhosis, MUTYH-associated polyposis (MAP), Lynch syndrome (LS), or Peutz-Jeghers syndrome (PJS).
- •History of other malignant tumors, or pathological diagnosis of colorectal inflammatory polyps, hyperplastic polyps, neuroendocrine tumors, neuroendocrine carcinoma, or mixed neuroendocrine-non-neuroendocrine neoplasms.
- •History of neurological or psychiatric disorders, such as epilepsy or depression.
- •Unqualified specimens, including hemolyzed serum samples or tissue samples that were not properly preserved in time.
研究组 & 干预措施
Colorectal cancer patients
Patients with pathologically confirmed colorectal cancer. Colorectal tumor and adjacent normal tissue specimens will be analyzed for SLC15A3 expression, or serum specimen will be analyzed for histidine-related metabolites, or whole blood samples will be analyzed for peripheral blood immune cell functions.
干预措施: Immunohistochemistry or immunofluorescence (Other)
Colorectal cancer patients
Patients with pathologically confirmed colorectal cancer. Colorectal tumor and adjacent normal tissue specimens will be analyzed for SLC15A3 expression, or serum specimen will be analyzed for histidine-related metabolites, or whole blood samples will be analyzed for peripheral blood immune cell functions.
干预措施: Flow cytometry (Other)
ICB responders
Patients with colorectal cancer who previously received PD-1 immune checkpoint blockade and achieved a clinical response. Tumor tissue will be analyzed for SLC15A3 expression, and serum specimen will be analyzed for histidine-related metabolites.
干预措施: Immunohistochemistry or immunofluorescence (Other)
ICB responders
Patients with colorectal cancer who previously received PD-1 immune checkpoint blockade and achieved a clinical response. Tumor tissue will be analyzed for SLC15A3 expression, and serum specimen will be analyzed for histidine-related metabolites.
干预措施: Serum metabolomic analysis or ELISA (Other)
ICB non-responders
Patients with colorectal cancer who previously received PD-1 immune checkpoint blockade and did not achieve a clinical response. Tumor tissue will be analyzed for SLC15A3 expression, and serum specimen will be analyzed for histidine-related metabolites.
干预措施: Immunohistochemistry or immunofluorescence (Other)
ICB non-responders
Patients with colorectal cancer who previously received PD-1 immune checkpoint blockade and did not achieve a clinical response. Tumor tissue will be analyzed for SLC15A3 expression, and serum specimen will be analyzed for histidine-related metabolites.
干预措施: Serum metabolomic analysis or ELISA (Other)
结局指标
主要结局
SLC15A3 expression
时间窗: Baseline archival tissue specimen from surgical resection or diagnostic biopsy.
SLC15A3 expression measured by immunohistochemistry (IHC) or immunofluorescence in formalin-fixed paraffin-embedded colorectal tumor and adjacent normal tissue specimens.
Serum histidine concentration
时间窗: Baseline and after 9 weeks (one round of treatment).
Serum histidine concentration measured using liquid chromatography-mass spectrometry (LC-MS) in serum samples collected before treatment initiation and, where available, after 9 weeks (one round of treatment).
次要结局
- Percentage of granzyme B-positive T cells(Baseline and after 9 weeks (one round of treatment).)
- Progression-free survival(5 years.)
- Overall survival(5 years.)
- Percentage of IFN-gamma-positive T cells(Baseline and after 9 weeks (one round of treatment).)
- Clinicopathological characteristics(Baseline at initial diagnosis or tissue collection.)
研究者
Jing-yuan Fang, MD, Ph. D
Professor Dr. Jing-yuan Fang
Shanghai Jiao Tong University School of Medicine