Abstract / Description
To explore the immune microenvironment of RAS‐mutated (RASmt) microsatellite stable (MSS) colon cancer (CC), we retrospectively performed whole exome sequencing, RNA sequencing, and robust digital pathology analyses and studied immune markers in a cohort of 161 patients treated with standard‐of‐care therapies with early stage disease (both fresh frozen and formalin‐fixed paraffin‐embedded [FFPE] samples) or 121 patients with metastatic setting (primary tumor FFPE samples). Only a small proportion of cases exhibited a highly infiltrated immune microenvironment, with a strong association between Immunoscore® (IS)‐high (13% of the samples) and Tumor Lymphocytes Infiltrating Score (TuLIS)‐high scores (25% of the samples). Immunoscore Immune‐Checkpoint (ISIC)‐high tumors (52% of the samples) shared a similar microenvironment composition to IS‐high and TuLIS‐like high tumors and displayed higher mutational burdens than ISIC‐low tumors. In conclusion, a substantial proportion of MSS RASmt CCs exhibit high ISIC scores, meriting evaluation in prospective trials of immunotherapy‐based combination regimens.