Deciphering the Renal tumOr microenvironment to PersonaLize immunE-targeted Treatment (DROPLET): transcriptomic profiling of primary and secondary lesions identified a potential crosstalk between MARCO+ macrophages and deregulated cancer-cell proliferation in mediating progression and therapy response of advanced renal cell carcinoта.

Immune checkpoint inhibitors (ICI) anti-programmed death-1 (αPD-1) have considerably improved the survival of patients with advanced clear cell renal cell carcinoma (ccRCC). However, a high number of patients fails to respond to ICI. Recent studies identified M2 macrophages (Mφs) as key players of ccRCC progression and ICI resistance. Despite preclinical studies showed that Mφ depletion enhances ICI efficacy, clinical results (combining ICI and Mφ-targeting agents (TAs)) reported no durable responses so far. Among factors limiting the clinical translation of Mφ-TAs are the diversity and plasticity of Mφs in tumors, as well as cancer cell intrinsic features, known to be crucial in dictating Mφs' phenotype. Thus, a better understanding of cancer cell-intrinsic mechanisms affecting Mφ polarization in ccRCC might help the identification novel druggable predictive biomarkers of response to ICI, as well as the design of therapeutic strategies to maximize ICI efficacy.