Role of stromal PD-L1 expression in colorectal liver metastasis

Background: and Aim The outcomes of immune checkpoint blockade for colorectal cancer (CRC) treatment are unsatisfactory. Furthermore, the efficacy of immune checkpoint blockade for liver metastasis of various cancer is poor. Here, we investigated the relationship between stromal programmed death-ligand 1 (PD-L1) expression and the prognosis of patients with colorectal cancer liver metastasis (CRLM). Methods: The present study enrolled 84 CRLM patients who underwent surgery (R0) for CRC. Immunohistochemistry was performed to analyze stromal PD-L1 expression in CRLM. Results: Stromal PD-L1 was expressed in 52.3% of CRLM samples, which was associated with a lower tumor grade (p=0.04) and fewer not optimally resectable metastases ( p= 0.04). Stromal PD-L1-positive patients had longer overall survival ( p= 0.003). Multivariate analysis identified stromal PD-L1 expression ( p= 0.008) and poorer differentiation (p<0.001) as independent prognostic indicators. Furthermore, stromal PD-L1 expression was correlated to a high number of tumor-infiltrating lymphocytes (TILs). Stromal PD-L1– and low TIL groups had shorter OS than stromal PD-L1+ and high TIL groups (46.6% vs. 81.8%, p= 0.05) Stromal PD-L1-positive patients had longer disease-free survival (DFS) ( p= 0.03) and time to surgical failure ( p= 0.001). Interestingly, stromal PD-L1 expression was positively related to the desmoplastic subtype ( p= 0.0002) and inversely related to the replacement subtype of the histological growth pattern ( p= 0.008). Conclusions: Stromal PD-L1 expression may be a significant prognostic marker for CRLM.