Mismatch repair deficient (MMRd) status is a robust predictive biomarker for immune checkpoint inhibitor (ICI) in endometrial cancer (EC). Nevertheless, half of the MMRd patients do not respond to ICI treatment. Most studies exploring biomarkers of response to ICI have been focusing on tumor- or immune cell-derived factors. To tackle this question from a different perspective, we deployed a mass spectrometry-based unbiased quantitative proteomics workflow to investigate the tumor microenvironment (TME) in ICI-Responder (R) versus Non-Responder (NR) MMRd EC patients, attempting to identify new predictive biomarkers of response.