<p>Analysis of tissue biopsy samples is the gold-standard approach to cancer diagnosis and patient selection for biomarker-guided therapies. Although spatial analyses of tumour tissue can provide important insights into local antitumour immune responses, repeated tumour biopsy is invasive and rarely feasible for monitoring dynamic immune responses over time. Technical advances have enabled multimodal analyses of cells and cellular products in peripheral blood samples, which can be obtained easily and repeatedly over the course of the disease. These liquid biopsy-based approaches cannot provide spatial information on the tumour immune microenvironment and tumour-derived material can be highly diluted in the circulation, yet they offer a unique opportunity to monitor systemic immune dynamics, anticipate responses to immunotherapies and detect emerging resistance to treatment. Thus, blood-based analyses might complement tumour tissue analysis. In this Review, we discuss insights on systemic antitumour immune responses that can be gained through the analysis of tumour-derived biomarkers in peripheral blood and/or circulating immune cells.</p>