Colorectal CancerNCT07586293
Histidine and Immunotherapy Response in Colorectal Cancer
An observational study of Colorectal Cancer, run by Jing-yuan Fang, MD, Ph. D.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Colorectal Cancer
- What is being tested?
- Immunohistochemistry or immunofluorescence, Serum metabolomic analysis or ELISA and Flow cytometry
- How many people
- 150 participants
- Where
- No sites listed yet
- Study dates
- May 2026to Jun 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: 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.
- Conditions
- Colorectal Cancer
- Being tested
- Immunohistochemistry or immunofluorescence, Serum metabolomic analysis or ELISA, Flow cytometry
- Keywords
- Colorectal cancer, Histidine, immune checkpoint blockade
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Immunohistochemistry or immunofluorescenceOther
Formalin-fixed paraffin-embedded (FFPE) colorectal tumor and adjacent normal tissue specimens will be analyzed for SLC15A3 expression by immunohistochemistry and/or immunofluorescence.
Serum metabolomic analysis or ELISAOther
Serum specimens from patients with colorectal cancer will be analyzed for histidine and related metabolites and selected biomarkers by metabolomics and/or ELISA.
Flow cytometryOther
Peripheral blood mononuclear cells (PBMCs) will be separated from whole blood samples and assessed for immune cell phenotype and functional markers by flow cytometry.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: Immunohistochemistry or immunofluorescence; Other: 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. Receives: Other: Immunohistochemistry or immunofluorescence; Other: Serum metabolomic analysis 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. Receives: Other: Immunohistochemistry or immunofluorescence; Other: Serum metabolomic analysis or ELISA |
What is being measured
The primary outcome is the main question the study is designed to answer.
SLC15A3 expression
SLC15A3 expression measured by immunohistochemistry (IHC) or immunofluorescence in formalin-fixed paraffin-embedded colorectal tumor and adjacent normal tissue specimens.
Measured: Baseline archival tissue specimen from surgical resection or diagnostic biopsy.
Serum histidine concentration
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).
Measured: Baseline and after 9 weeks (one round of treatment).
Secondary outcomes (5)
Progression-free survival
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.
Measured: 5 years.
Overall survival
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.
Measured: 5 years.
Percentage of IFN-gamma-positive T cells
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.
Measured: Baseline and after 9 weeks (one round of treatment).
Percentage of granzyme B-positive T cells
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.
Measured: Baseline and after 9 weeks (one round of treatment).
Clinicopathological characteristics
Clinicopathological characteristics of patients with colorectal cancer, including age, sex, tumor location, AJCC TNM stage, and histological grade, extracted from available medical records.
Measured: Baseline at initial diagnosis or tissue collection.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 May 2026
- Study startMay 2026 (estimated)
- Primary completionDec 2026 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Retrospective
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jing-yuan Fang, MD, Ph. D
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jing-yuan Fang, MD, Ph. D, Shanghai Jiao Tong University School of Medicine
- Investigators
- Jing-Yuan Fang, M.D., Principal investigator, Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07586293
- Sponsor's protocol ID
- KY2025-053-B
- Status last verified
- May 2026
- First submitted
- 24 Apr 2026
- Last updated
- 14 May 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanistic Study of Histidine-mediated Regulation of Antigen Presentation in Colorectal Cancer to Enhance Sensitivity to Immunotherapy
- ClinicalTrials.gov ID
- NCT07586293
- Acronym / sponsor ID
- KY2025-053-B
- Conditions
- Colorectal Cancer
- Keywords
- Colorectal cancer, Histidine, immune checkpoint blockade
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Jing-yuan Fang, MD, Ph. DUniversity, hospital or other
- Study start
- May 2026 (estimated)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 14 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Retrospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Colorectal cancer patients | – | Other: Immunohistochemistry or immunofluorescence, Other: Flow cytometryPatients 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. |
| ICB responders | – | Other: Immunohistochemistry or immunofluorescence, Other: Serum metabolomic analysis or ELISAPatients 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. |
| ICB non-responders | – | Other: Immunohistochemistry or immunofluorescence, Other: Serum metabolomic analysis or ELISAPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 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.
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (6 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Immunohistochemistry or immunofluorescenceFormalin-fixed paraffin-embedded (FFPE) colorectal tumor and adjacent normal tissue specimens will be analyzed for SLC15A3 expression by immunohistochemistry and/or immunofluorescence. | Other | Colorectal cancer patients, ICB non-responders, ICB responders |
| Serum metabolomic analysis or ELISASerum specimens from patients with colorectal cancer will be analyzed for histidine and related metabolites and selected biomarkers by metabolomics and/or ELISA. | Other | ICB non-responders, ICB responders |
| Flow cytometryPeripheral blood mononuclear cells (PBMCs) will be separated from whole blood samples and assessed for immune cell phenotype and functional markers by flow cytometry. | Other | Colorectal cancer patients |
Primary outcome
SLC15A3 expression
Time frame: 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
Time frame: 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).
5 secondary outcomes
Progression-free survival
Time frame: 5 years.
Overall survival
Time frame: 5 years.
Percentage of IFN-gamma-positive T cells
Time frame: Baseline and after 9 weeks (one round of treatment).
Percentage of granzyme B-positive T cells
Time frame: Baseline and after 9 weeks (one round of treatment).
Clinicopathological characteristics
Time frame: Baseline at initial diagnosis or tissue collection.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jing-Yuan Fang, M.D. principal investigator
Division of Gastroenterology and Hepatology, NHC Key Laboratory of Digestive Diseases, Renji Hospital, School of Medicine, Shanghai Jiao Tong University
Questions about this trial
What is this clinical trial studying?
An observational study of Colorectal Cancer, run by Jing-yuan Fang, MD, Ph. D.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 14 May 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Wan Du, M.D. ((86)13788972966, duwan2017@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
SLC15A3 expression (time frame: Baseline archival tissue specimen from surgical resection or diagnostic biopsy.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2026.