This study analyzed tumour microenvironment (TME) features and circulating biomarkers to understand patient responses to nivolumab plus cabozantinib versus sunitinib 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 citrullinated and MMP-degraded vimentin (VICM), reflecting macrophage activity, was prognostic for response to both therapies.

In the nivolumab plus cabozantinib 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.