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

NCT ID: NCT07069842

Last Updated: 2025-07-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

170 participants

Study Classification

OBSERVATIONAL

Study Start Date

2025-01-01

Study Completion Date

2026-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Gastric Cancer Immunotherapy

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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High-Response Group

Multiplex Immunofluorescence Technology

Intervention Type 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

Intervention Type 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

Intervention Type 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

Intervention Type DIAGNOSTIC_TEST

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

Non-Response Group

Multiplex Immunofluorescence Technology

Intervention Type 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

Intervention Type 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

Intervention Type 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

Intervention Type DIAGNOSTIC_TEST

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

Interventions

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Multiplex Immunofluorescence Technology

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.

Intervention Type DIAGNOSTIC_TEST

Co-Immunoprecipitation (Co-IP) Technology

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

Intervention Type DIAGNOSTIC_TEST

Immunohistochemistry

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.

Intervention Type DIAGNOSTIC_TEST

In situ hybridization with chromogenic detection

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

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Changzhi People's Hospital Affiliated to Changzhi Medical College

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jun Zhao

Role: STUDY_DIRECTOR

Changzhi People's Hospital

Locations

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Changzhi People's Hospital

Changzhi, Shanxi, China

Site Status RECRUITING

Countries

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China

Central Contacts

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Wenqing Hu

Role: CONTACT

+86-13509754125

Facility Contacts

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Jun Zhao

Role: primary

+86 13835578500

Other Identifiers

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2025K037

Identifier Type: -

Identifier Source: org_study_id

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