Tumour microenvironment and circulating biomarkers predict response to immunotherapy in advanced...

This study analysed tumour microenvironment (TME) features and circulating biomarkers to understand patient responses to nivolumab plus cabozantinib (NIVO+CABO) versus sunitinib (SUN) in advanced renal cell carcinoma within the Checkmate 9ER trial.

Using data from 150 patients, the research combined PD-L1 tumour staining, extracellular matrix (ECM) markers, immune cell populations, and histopathological features into a predictive logistic regression model. The ECM marker VICM, reflecting macrophage activity, was prognostic for response to both therapies. In the NIVO+CABO group, high VICM levels, elevated PD-L1 expression, increased plasma and cancer cell numbers at the tumour-stroma interface, alongside lower circulating collagen fragments and regulatory T cells, were associated with better treatment outcomes.

These findings highlight key biological determinants in the TME and circulation that can guide personalised therapy in advanced renal cell carcinoma.