Resistance to immune checkpoint inhibitors in gastric cancer
Kai Liu1, Shiman Yuan1, Chenyu Wang2
1The Clinical Medical College, Guizhou Medical University, Guiyang, China.
Abstract:
Gastric cancer (GC) is one of the most common gastrointestinal malignancies worldwide. In the past decade, with the development of early diagnostic techniques, a clear decline in GC incidence has been observed, but its mortality remains high. The emergence of new immunotherapies such as immune checkpoint inhibitors (ICIs) has changed the treatment of GC patients to some extent. However, only a small number of patients with advanced GC have a durable response to ICI treatment, and the efficacy of ICIs is very limited. Existing studies have shown that the failure of immunotherapy is mainly related to the development of ICI resistance in patients, but the understanding of the resistance mechanism is still insufficient. Therefore, clarifying the mechanism of GC immune resistance is critical to improve its treatment and clinical benefit. In this review, we focus on summarizing the mechanisms of primary or acquired resistance to ICI immunotherapy in GC from both internal and external aspects of the tumor. At the same time, we also briefly discuss some other possible resistance mechanisms in light of current studies.
Insights
Understanding immune resistance is key to improving gastric cancer treatment. This review explores how tumors develop resistance to immune checkpoint inhibitors (ICIs), hindering patient response.
Area of Science:
- Oncology
- Immunology
- Gastroenterology
Background:
- Gastric cancer (GC) remains a leading cause of cancer mortality despite diagnostic advances.
- Immune checkpoint inhibitors (ICIs) offer new treatment avenues for advanced GC but show limited durable responses.
- Resistance to ICIs is a major challenge, necessitating a deeper understanding of its mechanisms.
Purpose of the Study:
- To review and summarize the internal and external mechanisms of primary and acquired resistance to ICIs in gastric cancer.
- To highlight the critical need for understanding GC immune resistance to improve therapeutic outcomes.
- To discuss potential resistance mechanisms based on current research.
Main Methods:
- Literature review focusing on mechanisms of resistance to immune checkpoint inhibitors in gastric cancer.
- Analysis of internal (tumor-intrinsic) and external (tumor microenvironment) factors contributing to resistance.
- Synthesis of current research findings on gastric cancer immune resistance.
Main Results:
- Identified various internal and external factors contributing to primary and acquired resistance to ICIs in GC.
- Emphasized the insufficient understanding of GC immune resistance mechanisms.
- Highlighted the limited durable response rates to ICIs in advanced GC patients.
Conclusions:
- Clarifying GC immune resistance mechanisms is crucial for enhancing treatment efficacy and clinical benefit.
- Further research into resistance pathways is essential for developing more effective immunotherapies for gastric cancer.
- Addressing ICI resistance is vital for improving outcomes in patients with advanced gastric cancer.
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