Histidine and Immunotherapy Response in Colorectal Cancer
2026年5月12日 更新者：Jing-yuan Fang, MD, Ph. D
Mechanistic Study of Histidine-mediated Regulation of Antigen Presentation in Colorectal Cancer to Enhance Sensitivity to Immunotherapy
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.
研究概览
地位
尚未招聘
条件
研究类型
观察性的
注册 (估计的)
150
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习联系方式
- 姓名：Wan Du, M.D.
- 电话号码：(86)13788972966
- 邮箱：duwan2017@126.com
研究联系人备份
- 姓名：Youli Chen
- 电话号码：(86)13656503169
- 邮箱：chenylpetri@gmail.com
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
不
取样方法
非概率样本
研究人群
Patients with pathologically confirmed colorectal cancer who received care at the Department of Gastroenterology, Department of Oncology, or Department of General Surgery at Renji Hospital, Shanghai Jiao Tong University School of Medicine.
描述
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
队列和干预
团体/队列 |
干预/治疗 |
|---|---|
|
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.
|
Formalin-fixed paraffin-embedded (FFPE) colorectal tumor and adjacent normal tissue specimens will be analyzed for SLC15A3 expression by immunohistochemistry and/or immunofluorescence.
Peripheral blood mononuclear cells (PBMCs) will be separated from whole blood samples and assessed for immune cell phenotype and functional markers by flow cytometry.
|
|
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.
|
Formalin-fixed paraffin-embedded (FFPE) colorectal tumor and adjacent normal tissue specimens will be analyzed for SLC15A3 expression by immunohistochemistry and/or immunofluorescence.
Serum specimens from patients with colorectal cancer will be analyzed for histidine and related metabolites and selected biomarkers by metabolomics and/or ELISA.
|
|
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.
|
Formalin-fixed paraffin-embedded (FFPE) colorectal tumor and adjacent normal tissue specimens will be analyzed for SLC15A3 expression by immunohistochemistry and/or immunofluorescence.
Serum specimens from patients with colorectal cancer will be analyzed for histidine and related metabolites and selected biomarkers by metabolomics and/or ELISA.
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
SLC15A3 expression
大体时间：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.
|
Baseline archival tissue specimen from surgical resection or diagnostic biopsy.
|
|
Serum histidine concentration
大体时间：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).
|
Baseline and after 9 weeks (one round of treatment).
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Progression-free survival
大体时间：5 years.
|
Progression-free survival, defined as the time from initial diagnosis or treatment initiation to documented disease progression, recurrence, or death from any cause, whichever occurs first, in patients with colorectal cancer with available follow-up information.
|
5 years.
|
|
Overall survival
大体时间：5 years.
|
Overall survival, defined as the time from initial diagnosis or treatment initiation to death from any cause in patients with colorectal cancer with available follow-up information.
|
5 years.
|
|
Percentage of IFN-gamma-positive T cells
大体时间：Baseline and after 9 weeks (one round of treatment).
|
Peripheral blood mononuclear cells (PBMCs) from archived blood samples of patients with colorectal cancer will be assessed by flow cytometry to evaluate the percentage of IFN-gamma-positive T cells as a T cell effector function marker.
Samples collected before treatment initiation and, where available, after 9 weeks (one round of treatment) will be analyzed.
|
Baseline and after 9 weeks (one round of treatment).
|
|
Percentage of granzyme B-positive T cells
大体时间：Baseline and after 9 weeks (one round of treatment).
|
Peripheral blood mononuclear cells (PBMCs) from archived blood samples of patients with colorectal cancer will be assessed by flow cytometry to evaluate the percentage of granzyme B-positive T cells as a T cell effector function marker.
Samples collected before treatment initiation and, where available, after 9 weeks (one round of treatment) will be analyzed.
|
Baseline and after 9 weeks (one round of treatment).
|
|
Clinicopathological characteristics
大体时间：Baseline at initial diagnosis or tissue collection.
|
Clinicopathological characteristics of patients with colorectal cancer, including age, sex, tumor location, AJCC TNM stage, and histological grade, extracted from available medical records.
|
Baseline at initial diagnosis or tissue collection.
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员：Jing-Yuan Fang, M.D.、Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (估计的)
2026年5月1日
初级完成 (估计的)
2026年12月1日
研究完成 (估计的)
2027年6月1日
研究注册日期
首次提交
2026年4月24日
首先提交符合 QC 标准的
2026年5月12日
首次发布 (实际的)
2026年5月14日
研究记录更新
最后更新发布 (实际的)
2026年5月14日
上次提交的符合 QC 标准的更新
2026年5月12日
最后验证
2026年5月1日
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- KY2025-053-B
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