• Harnessing Liquid Biopsy for Real-Time Monitoring of Immune Checkpoint Inhibitor Response in Cancer Treatment: A Pathway to Personalized Immunotherapy
  • Ayda seyedmohammadi,1,*
    1. Department of Cell and Molecular Biology, Faculty of Natural Sciences, Tabriz National University, Tabriz, Iran


  • Introduction: Circulating biomarker assays offer a minimally invasive method for the immediate surveillance of immunomodulatory checkpoint inhibitor (ICI) responses in cancer immunotherapy. This approach utilizes cell-free tumor DNA (ctDNA), circulating tumor cells (CTCs), and other biomarkers found in bodily fluids, primarily blood, to provide insights into tumor evolution and therapeutic effectiveness. Conventional imaging methods often struggle to accurately assess patient responses, highlighting the need for innovative strategies that enable adaptive tracking of treatment outcomes. Circulating biomarker assays present a promising solution by providing real-time data on tumor genetics and immune profiles, facilitating tailored therapeutic strategies to meet individual patient needs and aiding in the proactive identification of resistance pathways. Immune checkpoint inhibitors have significantly improved cancer treatment by enhancing the body’s immune response against tumors. However, the variability in patient responses necessitates a deeper understanding of predictive biomarkers for effective therapies. Current assessment techniques often rely on imaging and tissue biopsies, which may not capture immediate changes in tumor biology or immune status. Circulating biomarker assays provide a dynamic alternative, allowing for continuous evaluation of tumor progression and immune engagement throughout treatment. This study aims to explore the potential of circulating biomarker assays for real-time monitoring of ICI responses, enhancing the precision of immuno-oncological treatment by providing timely insights into therapeutic responses.
  • Methods: This review evaluates the role of liquid biopsy in managing malignancies treated with ICIs, emphasizing studies that utilize long-term frameworks to track patients at various time points and document changes in tumor characteristics. Liquid biopsy specimens are obtained through minimally invasive venipuncture, employing advanced techniques such as next-generation sequencing and digital droplet PCR. The review focuses on identifying biomarkers predictive of ICI efficacy, including tumor mutational burden and microsatellite instability, which are analyzed through genomic profiling to establish correlations with clinical outcomes. Included studies involve cancer patients receiving ICIs who undergo liquid biopsies to collect circulating free DNA (cfDNA), CTCs, and exosomes. High-throughput genomic sequencing analyzes cfDNA for mutations and neoantigen identification, while immune profiling assesses T cell activity and immunosuppressive factors within the tumor microenvironment. The review correlates clinical outcomes, such as progression-free survival and overall survival, with liquid biopsy findings and evaluates the prognostic significance of identified biomarkers. Furthermore, the review synthesizes literature on liquid biopsy applications across various cancer types, particularly lung and colorectal cancers, discussing emerging technologies like mass spectrometry and flow cytometry that enhance the detection and analysis of tumor-derived materials. By integrating these methodologies with ICI therapy, clinicians can effectively monitor treatment responses and adjust therapeutic strategies based on real-time data.
  • Results: The outcomes of this review highlight the substantial role of liquid biopsy in tracking therapeutic responses to ICIs and predicting patient outcomes. Initial findings suggest a strong relationship between specific liquid biopsy biomarkers, particularly elevated ctDNA levels, and positive patient responses to ICIs. This connection underscores the potential of liquid biopsies as reliable indicators of treatment efficacy, with studies showing that patients with favorable biomarker profiles exhibit significantly improved response rates to ICIs compared to those without such profiles. The accuracy of liquid biopsy in predicting both short-term and long-term treatment outcomes has been validated through comprehensive data analysis. Results indicate that liquid biopsy enables real-time monitoring of emerging resistance mechanisms during immunotherapy. By identifying genetic alterations associated with resistance early, clinicians can adjust treatment regimens timely, potentially enhancing patient outcomes.
  • Conclusion: This review underscores the pivotal role of liquid biopsy in linking biomarker dynamics with ICI response monitoring, highlighting its potential to revolutionize personalized cancer immunotherapy. Liquid biopsy serves as a valuable real-time monitoring tool, offering insights into tumor evolution and individual immune responses. By integrating liquid biopsy into routine clinical practice, clinicians can tailor immunotherapy strategies based on real-time insights into tumor biology and immune interactions, leading to more effective and personalized treatment options. Future research should focus on validating liquid biopsy technologies across diverse cancer types and larger patient cohorts, investigating novel biomarkers to enhance understanding of tumor-immune interactions. Addressing challenges such as standardizing liquid biopsy procedures and conducting large-scale studies will be essential for establishing robust clinical guidelines. In summary, leveraging liquid biopsy for continuous monitoring of ICI responses represents a significant advancement in precision oncology, ultimately improving patient outcomes and quality of life for those undergoing immunotherapy.
  • Keywords: Liquid Biopsy,ImmuneCheckpoint Inhibitors(ICIs),CellFree Tumor DNA(ctDNA),Personalized Immunotherapy