The involvement of SPP1+ macrophages in this exclusionary barrier has been observed across multiple cancer types, including colorectal cancer (10, 16, 73), hepatocellular carcinoma (7, 18, 98, 99), non-small cell lung cancer (74, 79), gastric carcinoma (100), prostate cancer (76), esophageal squamous cell carcinoma (13), and bladder cancer (70). This evidence concerns the gene SPP1 and colorectal cancer.