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Biomarkers for Immunotherapy in Driver-Gene-Negative Advanced NSCLC
Yiyi Huang1, Yi-Fung Chau1, Hua Bai1
1CAMS Key Laboratory of Translational Research on Lung Cancer, State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.
Abstract:
Outcome improvement in patients with driver-gene-negative advanced non-small cell lung cancer (NSCLC) has been significantly enhanced through targeting the immune system, specifically the PD-L1/PD-1 axis. Nevertheless, only a subset of patients with advanced NSCLC may derive benefits from immuno-monotherapy or immunotherapy combined with chemotherapy. Hence, in order to identify patients who will gain the maximum advantage from immunotherapy, it is crucial to investigate predictive biomarkers. This review provides a summary of the currently identified biomarkers associated with the extent of benefit from immuno-monotherapy or immunotherapy combined with chemotherapy in patients with advanced NSCLC. These biomarkers can be categorized into three groups: tumor-related, tumor-microenvironment-related, and host-factor-related.Tumor-related factors include PD-L1 expression, tumor mutational burden and specific genetic mutations, while tumor-microenvironment-related factors include extracellular vesicles and T-cell receptors, and host-related factors include systemic inflammation, circulating fatty acid profile, and the microbiome.
Insights
Identifying biomarkers is key to improving outcomes for advanced non-small cell lung cancer (NSCLC) patients treated with immunotherapy. This review summarizes predictive biomarkers for immunotherapy benefit in NSCLC.
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Immunotherapy targeting the PD-L1/PD-1 axis has improved outcomes for advanced non-small cell lung cancer (NSCLC) patients.
- However, only a subset of patients benefit from current immunotherapies, necessitating predictive biomarker identification.
Purpose of the Study:
- To review and categorize identified biomarkers predicting patient benefit from immunotherapy in advanced NSCLC.
- To guide the selection of patients most likely to gain advantage from immuno-monotherapy or combination chemotherapy.
Main Methods:
- Literature review of studies identifying biomarkers for immunotherapy response in advanced NSCLC.
- Categorization of biomarkers into tumor-related, tumor-microenvironment-related, and host-factor-related groups.
Main Results:
- Tumor-related biomarkers include PD-L1 expression, tumor mutational burden, and specific mutations.
- Tumor-microenvironment biomarkers involve extracellular vesicles and T-cell receptors.
- Host-related factors encompass systemic inflammation, fatty acid profiles, and the microbiome.
Conclusions:
- Biomarkers are crucial for optimizing immunotherapy selection in advanced NSCLC.
- A multi-category approach (tumor, microenvironment, host) is essential for comprehensive prediction.
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