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Updated: Jun 23, 2025
Monitoring PD-1-Blocking Antibodies Bound to T Cells Derived from a Drop of Peripheral Blood
Published on: February 5, 2020
Advances and prospects of biomarkers for immune checkpoint inhibitors
Hirohito Yamaguchi1, Jung-Mao Hsu2, Linlin Sun3
1Graduate Institute of Cell Biology, China Medical University, Taichung City 406040, Taiwan; Graduate Institute of Biomedical Sciences and Institute of Biochemistry and Molecular Biology, China Medical University, Taichung City 406040, Taiwan; Cancer Biology and Precision Therapeutics Center and Research Center for Cancer Biology, China Medical University, Taichung City 40402, Taiwan.
Abstract:
Immune checkpoint inhibitors (ICIs) activate anti-cancer immunity by blocking T cell checkpoint molecules such as programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Although ICIs induce some durable responses in various cancer patients, they also have disadvantages, including low response rates, the potential for severe side effects, and high treatment costs. Therefore, selection of patients who can benefit from ICI treatment is critical, and identification of biomarkers is essential to improve the efficiency of ICIs. In this review, we provide updated information on established predictive biomarkers (tumor programmed death-ligand 1 [PD-L1] expression, DNA mismatch repair deficiency, microsatellite instability high, and tumor mutational burden) and potential biomarkers currently under investigation such as tumor-infiltrated and peripheral lymphocytes, gut microbiome, and signaling pathways related to DNA damage and antigen presentation. In particular, this review aims to summarize the current knowledge of biomarkers, discuss issues, and further explore future biomarkers.
Insights
Identifying biomarkers is crucial for effective immune checkpoint inhibitor (ICI) cancer therapy. This review details established and emerging biomarkers to improve patient selection and treatment outcomes for ICI therapy.
Area of Science:
- Oncology
- Immunology
- Biomarker Research
Background:
- Immune checkpoint inhibitors (ICIs) harness anti-cancer immunity by targeting molecules like PD-1 and CTLA-4.
- While ICIs offer durable responses, challenges include low response rates, severe side effects, and high costs, necessitating better patient selection.
Purpose of the Study:
- To provide an updated review of predictive biomarkers for ICI therapy.
- To discuss current challenges and explore future directions in biomarker discovery for ICIs.
Main Methods:
- Literature review of established and emerging biomarkers for ICI treatment.
- Synthesis of current knowledge on biomarkers including PD-L1 expression, MSI, TMB, and immune cell infiltration.
Main Results:
- Established biomarkers include tumor PD-L1 expression, DNA mismatch repair deficiency, microsatellite instability-high, and tumor mutational burden.
- Emerging biomarkers under investigation encompass tumor-infiltrated lymphocytes, peripheral lymphocytes, gut microbiome, and pathways related to DNA damage and antigen presentation.
Conclusions:
- Biomarker identification is critical for optimizing ICI efficacy and patient selection.
- Further research into novel biomarkers is essential to overcome ICI treatment limitations and improve patient outcomes.
