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NCT Number: NCT07586293

Histidine and Immunotherapy Response in Colorectal Cancer

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.

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Key information

Conditions

Colorectal Cancer Colonic Diseases Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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.

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.

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.

Primary outcomes

  1. 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.

  2. 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).

Secondary outcomes

  1. Progression-free survival

    Time frame: 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.

  2. Overall survival

    Time frame: 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.

  3. Percentage of IFN-gamma-positive T cells

    Time frame: 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.

  4. Percentage of granzyme B-positive T cells

    Time frame: 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.

  5. Clinicopathological characteristics

    Time frame: 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Wan Du, M.D.

CONTACT

[email protected]

(86)13788972966

Youli Chen

CONTACT

[email protected]

(86)13656503169

Sponsors and collaborators

Lead sponsor

Jing-yuan Fang, MD, Ph. D

Other

Registry information

Official study title

Mechanistic Study of Histidine-mediated Regulation of Antigen Presentation in Colorectal Cancer to Enhance Sensitivity to Immunotherapy

Important dates

Study start
2026
Primary completion
2026
Study completion
2027
First posted
May 14, 2026
Registry last updated
May 14, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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