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Updated: Nov 30, 2025
Monitoring the Cancer-Immunity Cycle and Exploring Tumor Microenvironment Dynamics
Published on: June 7, 2024
Towards a Systems Immunology Approach to Unravel Responses to Cancer Immunotherapy
Laura Bracci1, Alessandra Fragale1, Lucia Gabriele1
1Tumor Immunology Unit, Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
Abstract:
Immunotherapy, particularly immune checkpoint blockade and chimeric antigen receptor (CAR)-T cells, holds a great promise against cancer. These treatments have markedly improved survival in solid as well as in hematologic tumors previously considered incurable. However, durable responses occur in a fraction of patients, and existing biomarkers (e.g. PD-L1) have shown limited prediction power. This scenario highlights the need to dissect the complex interplay between immune and tumor cells to identify reliable biomarkers of response to be used for patients' selection. In this context, systems immunology represents indeed the new frontier to address important clinical challenges in biomarker discovery. Through the integration of multiple layers of data obtained with several high-throughput approaches, systems immunology may give insights on the vast range of inter-individual differences and on the influences of genes and factors that cooperatively shape the individual immune response to a given treatment. In this Mini Review, we give an overview of the current high-throughput methodologies, including genomics, epigenomics, transcriptomics, metabolomics, proteomics, and multi-parametric phenotyping suitable for systems immunology as well as on the key steps of data integration and biological interpretation. Additionally, we review recent studies in which multi-omics technologies have been used to characterize mechanisms of response and to identify powerful biomarkers of response to checkpoint inhibitors, CAR-T cell therapy, dendritic cell-based and peptide-based cancer vaccines. We also highlight the need of favoring the collaboration of researchers with complementary expertise and of integrating multi-omics data into biological networks with the final goal of developing accurate markers of therapeutic response.
Insights
Systems immunology integrates multi-omics data to discover biomarkers for cancer immunotherapy. This approach enhances patient selection for treatments like immune checkpoint blockade and CAR-T cell therapy, improving response prediction.
Area of Science:
- Integrative immunology and cancer research.
- Biomarker discovery for cancer immunotherapy.
Background:
- Cancer immunotherapies, including immune checkpoint blockade and CAR-T cells, show promise but have limited durable response rates.
- Current biomarkers like PD-L1 have insufficient predictive power, necessitating improved patient selection strategies.
- Understanding the complex immune-tumor cell interplay is crucial for identifying reliable response biomarkers.
Purpose of the Study:
- To provide an overview of systems immunology approaches for biomarker discovery in cancer immunotherapy.
- To review high-throughput methodologies and data integration strategies for analyzing complex biological data.
- To highlight the application of multi-omics technologies in identifying biomarkers for various immunotherapies.
Main Methods:
- Review of current high-throughput methodologies: genomics, epigenomics, transcriptomics, metabolomics, proteomics, and multi-parametric phenotyping.
- Discussion of data integration and biological interpretation techniques within systems immunology.
- Analysis of recent studies utilizing multi-omics data for biomarker identification in cancer immunotherapy.
Main Results:
- Multi-omics technologies enable a comprehensive understanding of inter-individual immune response variations.
- These approaches have successfully identified powerful biomarkers for checkpoint inhibitors, CAR-T cell therapy, and cancer vaccines.
- Systems immunology provides insights into mechanisms of response and resistance to cancer immunotherapies.
Conclusions:
- Systems immunology is a frontier for addressing clinical challenges in cancer immunotherapy biomarker discovery.
- Integration of multi-omics data into biological networks is essential for developing accurate therapeutic response markers.
- Enhanced collaboration among researchers with diverse expertise is vital for advancing biomarker development.
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