Rise of PD‐L1 expression during metastasis of colorectal cancer: Implications for immunotherapy

OBJECTIVE Programmed death‐ligand 1 (PD‐L1) expression in colorectal cancer (CRC) was implicated in predicting anti‐PD‐1/PD‐L1 therapy efficacy. However, therapeutic response has also been found in patients without PD‐L1 expression in the primary tumor. In the present study, we aimed to clarify the prevalence of PD‐L1 in primary and metastatic CRC. METHODS The expression of PD‐L1 was determined by immunohistochemistry in matched primary and metastatic CRC. RESULTS PD‐L1 expression was significantly more prevalent in metastatic CRCs than in primary tumors, and the expression of PD‐L1 in primary CRC may not represent the tumors that spread to distant organs. Positive expression of PD‐L1 was found in 81.8% of metastatic CRC, being significantly more prevalent than in primary CRC (40.9%; P = 0.012, Fisher’s exact test). While comparing the primary and metastatic lesions of the same patients, we found that PD‐L1 expression frequently increased during the metastatic process. However, PD‐L1 expression was rarely decreased in metastatic lesions. Intratumoral heterogeneity expression of PD‐L1 was found in both metastatic CRC (22.2%) and primary CRCs (33.3%). PD‐L1 was prevalently expressed in metastatic CRC, and increased PD‐L1 expression was frequently found in metastatic CRC as compared to primary tumors. CONCLUSION PD‐L1 expression in metastatic CRC should be considered as an independent factor while evaluating the suitability of patients for immunotherapy.