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

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.

Conditions

• Gastric Cancer
• Immunotherapy

Interventions

DIAGNOSTIC_TEST

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.

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

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.

DIAGNOSTIC_TEST

In situ hybridization with chromogenic detection

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

Sponsors & Collaborators

• Changzhi People's Hospital Affiliated to Changzhi Medical College

  lead OTHER

Principal Investigators

• Jun Zhao · Changzhi People's Hospital

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-01-01

Primary Completion

2026-01-01

Completion

2026-12-31

Countries

• China

Study Locations