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

NCT07069842 — Recruiting, 170 participants, Changzhi People's Hospital Affiliated to Changzhi Medical College

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Registry	NCT07069842
Status	Recruiting
Study type	Observational
Enrollment	170 (Estimated)
Sponsor	Changzhi People's Hospital Affiliated to Changzhi Medical College (Other)
Conditions	Gastric Cancer, Immunotherapy
Interventions	Multiplex Immunofluorescence Technology, Co-Immunoprecipitation (Co-IP) Technology, Immunohistochemistry, In situ hybridization with chromogenic detection (Diagnostic test)
Dates	start 2025-01-01, primary completion 2026-01-01 (estimated), completion 2026-12-31 (estimated), first posted 2025-07-17, last updated 2025-07-17
Locations	1 site in China

-Summary

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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+Arms and interventions

Arm	Type	Interventions	Description
High-Response Group		Diagnostic Test: Multiplex Immunofluorescence Technology; Diagnostic Test: Co-Immunoprecipitation (Co-IP) Technology; Diagnostic Test: Immunohistochemistry; Diagnostic Test: In situ hybridization with chromogenic detection
Non-Response Group		Diagnostic Test: Multiplex Immunofluorescence Technology; Diagnostic Test: Co-Immunoprecipitation (Co-IP) Technology; Diagnostic Test: Immunohistochemistry; Diagnostic Test: In situ hybridization with chromogenic detection

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.

+Outcome measures

Primary outcomes

Response to Immunotherapy in Solid Tumors [1 year]

+Eligibility

Sex: All, ages: 18 Years to 75 Years

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

+Locations (1)

Facility	City	Country	Status
Changzhi People's Hospital	Changzhi, Shanxi	China	Recruiting

+Investigators

Jun Zhao, Study director, Changzhi People's Hospital