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NCT Number: NCT07069842

The Construction of a Predictive Model for Gastric Cancer Immunotherapy Response Based on Tumor-Infiltrating Lymphocytes (TILs) and Histone H3K4me3 in the Tumor Microenvironment

Gastric cancer is one of the cancers with a high mortality rate globally, and its treatment outcomes urgently need to be improved. The emergence of immunotherapy has broken through the bottleneck of chemotherapy for gastric cancer. However, the therapeutic efficacy of immunotherapy varies significantly among patients and still needs to be enhanced. Extensive research has demonstrated that the efficacy of immunotherapy for gastric cancer is significantly influenced by the tumor microenvironment (TME) and epigenetic modifications. The dynamic changes in tumor-infiltrating lymphocytes (TILs) and histone H3K4me3 may reshape the TME, thereby affecting the efficacy of immunotherapy. Based on these findings, this study proposes the scientific hypothesis that the density and spatial distribution of TILs in the TME, as well as the level of H3K4me3 modification, may serve as key biomarkers for predicting the response of gastric cancer patients to immunotherapy. This project aims to delve into the potential mechanisms by which TILs and H3K4me3 enhance the efficacy of immune checkpoint inhibitors (ICIs) and to construct a predictive model for the response to immunotherapy in gastric cancer based on TILs and H3K4me3. The establishment of this model will help identify the patient population most likely to benefit from immunotherapy, facilitate personalized treatment, provide new ideas and approaches for the treatment of gastric cancer, and advance the field of gastric cancer immunotherapy.

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Key information

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Changzhi People's Hospital

Changzhi, Shanxi, 046000, China

Location status: Recruiting

Location contact

Jun Zhao

CONTACT

[email protected]

+86 13835578500

Xiaoling Zhang

SUB_INVESTIGATOR

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • 1.Diagnosed with histologically confirmed locally advanced (LA) unresectable or metastatic gastric/gastroesophageal junction (G/GEJ) adenocarcinoma, aged 18 to 75 years.

2.Scheduled to receive first-line therapy with ICIs plus chemotherapy with or without anti-her-2 therapy.

3.Have at least one measurable lesion as the target lesion per iRECIST V.1.1 criteria and an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Exclusion criteria

  • 1.History of secondary malignant tumors within 3 years prior to study initiation, or other types of brain/meningeal metastatic tumors.

2.Presence of concomitant diseases that, in the investigator's judgment, may seriously jeopardize their safety or interfere with study completion

Treatment and study plan

Multiplex Immunofluorescence Technology

Diagnostic Test

Detect the levels of TILs (using Multiplex Immunofluorescence Technology) and H3K4me3 (using Co-Immunoprecipitation Technology) in fresh tissue samples of patients before and after immunotherapy combination treatment.Meanwhile, detect the expression of cytokines, NLR, PLR, SII, and tumor markers in peripheral blood.Immunohistochemical staining was used to detect the expression of Her-2, PD-L1, MMR (MLH1, PMS2, MSH2, MSH6), KMTs (MLL1, MLL2, SETD1A, SETD1B), specific subunits of the SET1/MLL complex (MEN1, CFP1, WDR5, RBBP5, ASH2L, DPY30), and KDMs (KDM5A, KDM5B) in patient tissue specimens.In situ hybridization with chromogenic detection was performed to assess the EBER status.

Co-Immunoprecipitation (Co-IP) Technology

Diagnostic Test

Detect the levels of TILs (using Multiplex Immunofluorescence Technology) and H3K4me3 (using Co-Immunoprecipitation Technology) in fresh tissue samples of patients before and after immunotherapy combination treatment

Immunohistochemistry

Diagnostic Test

Immunohistochemical staining was used to detect the expression of Her-2, PD-L1, MMR (MLH1, PMS2, MSH2, MSH6), KMTs (MLL1, MLL2, SETD1A, SETD1B), specific subunits of the SET1/MLL complex (MEN1, CFP1, WDR5, RBBP5, ASH2L, DPY30), and KDMs (KDM5A, KDM5B) in patient tissue specimens.

In situ hybridization with chromogenic detection

Diagnostic Test

In situ hybridization with chromogenic detection was performed to assess the EBER status.

Primary outcomes

  1. Response to Immunotherapy in Solid Tumors

    Time frame: 1 year

Study contacts

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

Wenqing Hu

CONTACT

[email protected]

+86-13509754125

Sponsors and collaborators

Lead sponsor

Changzhi People's Hospital Affiliated to Changzhi Medical College

Other

Registry information

Important dates

Study start
2025
Primary completion
2026
Study completion
2026
First posted
Jul 17, 2025
Registry last updated
Jul 17, 2025

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

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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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