As the current representative approach for cancer immunotherapy, immune checkpoint blockade (ICB), like anti-PD-1, is effective in a subset of metastatic CRC patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H), but not in metastatic CRC patients with mismatch repair–proficient (pMMR)/microsatellite stable (MSS), which represents 95% of metastatic CRC cases [3–5]. The gene discussed is PDCD1; the disease is colorectal carcinoma.