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.
Highlights
In the last few years, immune-based cancer therapies have been rediscovered as powerful clinical strategies against cancer
Systems immunology provides unprecedented opportunities for biomarker discovery stemming from the integration and statistical analysis of large datasets generated by highthroughput analysis of biological samples either at single cell or at bulk tissue level
The vast majority of recent immunotherapeutic studies still rely on the use of a single omic approach at a time
Summary
In the last few years, immune-based cancer therapies have been rediscovered as powerful clinical strategies against cancer. This breakthrough has begun with the discovery and clinical application of immune-checkpoint inhibitors (ICIs) that have changed radically the management of several types of once considered incurable cancers [1]. We will provide an overview of the key technological approaches exploited by systems immunology analysis and will provide examples of application in the urgent search for reliable markers to select cancer patients for personalized immunotherapy approaches [10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
