Advances Toward Liquid Biopsy Profiling of Antitumor Immune Responses

Tumour biopsy remains the clinical gold standard for diagnosing cancer and guiding biomarker-based treatment choices. By interrogating the tumour itself, researchers can map local immune architecture and capture spatial patterns that often explain why some patients respond to immunotherapy while others do not. Yet this approach has a major limitation: repeated sampling is invasive, rarely feasible, and typically fails to capture how immunity evolves week by week during treatment.

Over the past few years, “liquid biopsy” technologies have expanded the toolkit for monitoring cancer beyond tissue. Instead of relying on a single snapshot from the tumour site, these methods analyze tumour-derived signals and circulating immune cells in peripheral blood. Because blood collection is minimally invasive, clinicians can sample longitudinally and follow systemic immune dynamics across the course of disease.

The trade-off is clear. Liquid biopsy generally cannot reproduce the spatial resolution of tissue analyses, so it cannot directly describe how immune cells are organized within the tumour microenvironment. In addition, tumour-derived material in blood can be diluted and heterogeneous, challenging sensitivity and interpretation—especially when disease burden is low.

Despite these constraints, blood-based profiling offers a compelling advantage: it can act as an early warning system for systemic immune shifts. Multimodal assays can quantify cellular populations, track activation or exhaustion states in circulating immune subsets, and measure soluble tumour-associated products shed into circulation. Together, these readouts can reflect whether the host immune system is mounting an effective response.

Importantly, such systemic immune monitoring may help anticipate how patients will respond to immunotherapies. By detecting emerging patterns—such as changes in immune-cell composition or alterations in tumour-linked biomarkers—clinicians may gain a window into treatment efficacy before clinical outcomes fully manifest.

Liquid biopsy also holds promise for detecting resistance as it arises. As tumours adapt, the immune landscape and tumour-derived signals in blood may change, providing a route to identify resistance trajectories earlier than traditional imaging or single time-point biopsies.

In this Review, Pantel, Masmoudi and Alix-Panabières describe how combining tumour-derived biomarkers from peripheral blood with analyses of circulating immune cells can complement tumour tissue studies. The overarching message is that systemic immune monitoring can supplement spatial tumour insights rather than replace them.

Ultimately, integrating liquid biopsy with tumour biopsy could enable a more complete, time-resolved view of antitumour immunity—linking local biology to global immune dynamics. That synergy may improve patient selection, guide therapy adjustments, and refine strategies for managing immunotherapy over time.