Histidine and Immunotherapy Response in Colorectal Cancer

NCT07586293 | Not Yet Recruiting

• 1 other identifier: KY2025-053-B
• Study Type: observational
• Target: 150
• Locations: 0 countries
• Sites: N/A

Brief 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, 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

Keywords

Colorectal cancer; Histidine; immune checkpoint blockade

Outcome Measures

Primary Outcomes (2)

• SLC15A3 expression

  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

  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).

Secondary Outcomes (5)

• 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).

• Percentage of granzyme B-positive T cells

  Baseline and after 9 weeks (one round of treatment).

• Clinicopathological characteristics

  Baseline at initial diagnosis or tissue collection.

Study Arms (3)

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.

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.

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.

Other: Immunohistochemistry or immunofluorescence; Other: Serum metabolomic analysis or ELISA

Interventions

Immunohistochemistry or immunofluorescence OTHER

Formalin-fixed paraffin-embedded (FFPE) colorectal tumor and adjacent normal tissue specimens will be analyzed for SLC15A3 expression by immunohistochemistry and/or immunofluorescence.

Colorectal cancer patients; ICB non-responders; ICB responders

Serum metabolomic analysis or ELISA OTHER

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; ICB responders

Flow cytometry OTHER

Peripheral blood mononuclear cells (PBMCs) will be separated from whole blood samples and assessed for immune cell phenotype and functional markers by flow cytometry.

Colorectal cancer patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Jing-yuan Fang, MD, Ph. D: lead

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood specimen; Serum specimen; Surgical tissue specimen

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Immunohistochemistry; Fluorescent Antibody Technique; Enzyme-Linked Immunosorbent Assay; Flow Cytometry

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Histocytochemistry; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Histological Techniques; Investigative Techniques; Immunologic Techniques; Immunoenzyme Techniques; Immunoassay; Immunosorbent Techniques; Molecular Probe Techniques; Cell Separation; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical

Study Officials

• 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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wan Du, M.D.

CONTACT

(86)13788972966; duwan2017@126.com

Youli Chen

CONTACT

(86)13656503169; chenylpetri@gmail.com

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor Dr. Jing-yuan Fang

Study Record Dates

• First Submitted: April 24, 2026
• First Posted: May 14, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: May 14, 2026

Record last verified: 2026-05