Liquid biopsy for cancer immunotherapy: Biomarkers to predict and monitor response upon immune checkpoint blockade

Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment, offering durable responses in a specific subset of patients. However, the lack of reliable indicators or monitoring methods to estimate ICI efficacy remains a significant challenge. Various liquid biopsy assays have emerged as promising tools to overcome these limitations due to their non-invasive nature and ability to capture tumor heterogeneity. This review provides a systematic and comprehensive overview of clinical studies, categorizing liquid biopsy biomarkers—including ctDNA, CTCs, soluble proteins, and exosomes—based on their clinical applications and presenting specific, detailed findings from the most up-to-date research. Additionally, this review addresses the limitations of each biomarker, as highlighted by conflicting results in some clinical studies, and explores prospects for overcoming these challenges through advanced technologies and integrated approaches. By offering a detailed classification of clinical studies and actionable perspectives, this review serves as a guideline for researchers and clinicians entering the field, providing a clear framework for addressing current challenges and advancing the potential of liquid biopsy biomarkers in ICI treatment.