Programmed death-ligand 1 expression in the tumour stroma of colorectal liver oligometastases and its association with prognosis after liver resection

Abstract

Background The clinical value of programmed death-ligand 1 (PD-L1) expression in colorectal liver oligometastases (CLOs) remains undefined. This study aimed to detect PD-L1 in the microenvironment of CLOs and determine its association with patient prognosis. Methods We collected 126 liver-resection specimens from CLO patients who underwent curative liver resection between June 1999 and December 2016. Immunohistochemistry (IHC) was performed to assess PD-L1 expression in paraffin-embedded specimens. Overall survival (OS) and recurrence-free survival (RFS) were analysed using the Kaplan–Meier method and log-rank test. Results PD-L1 was mainly expressed in the stroma of liver oligometastases. Patients with high PD-L1 expression had a higher proportion of clinical-risk scores (CRSs) of 2–4 (67.7% vs 40.4%; P = 0.004). With a median 58-month follow-up, patients with high PD-L1 expression had a significantly lower 3-year OS rate (65.5% vs 92.7%; P = 0.001) and 3-year RFS rate (34.7% vs 83.8%; P < 0.001) than patients with low PD-L1 expression. Multivariate Cox analysis demonstrated that high PD-L1 expression (hazard ratio [HR] = 3.581; 95% confidence interval [CI] 2.301–9.972; P = 0.015), CRS 2–4 (HR = 6.960; 95% CI 1.135–42.689; P = 0.036) and increased preoperative CA19-9 (HR = 2.843; 95% CI 1.229–6.576; P = 0.015) were independent risk factors for OS. High PD-L1 expression (HR = 4.815; 95% CI 2.139–10.837; P < 0.001) and lymph-node metastasis (HR = 2.115; 95% CI 1.041–4.297; P = 0.038) were independent risk factors for RFS. Conclusion This study found that PD-L1 was commonly expressed in the tumour stroma of CLOs and high PD-L1 expression was associated with poor prognosis.

Role of stromal PD-L1 expression in colorectal liver metastasis

“…However, the prognostic value of stromal PD-L1 expression in CRC [ 16 , 17 ] and tumor PD-L1 expression [ 6 , 36 ] is highly debated. Only one study reported the stromal PD-L1 expression in colorectal liver oligometastasis [ 20 ]. Unlike our study results, PD-L1 expression was correlate to poor prognosis in patients with liver oligometastasis.…”

“…Stromal PD-L1 expression was higher than in the primary site in patients with synchronous metastasis, but its prognostic value was not elucidated. Furthermore, one study of stromal PD-L1 expression focused on a limited number of patients with colorectal liver oligometastasis defined as no more than five liver metastases [ 20 ]. Therefore, we evaluated the influence of stromal PD-L1 expression on CRLM and its prognostic value.…”

Navigating through the PD-1/PDL-1 Landscape: A Systematic Review and Meta-Analysis of Clinical Outcomes in Hepatocellular Carcinoma and Their Influence on Immunotherapy and Tumor Microenvironment

“… Subgroup hazard ratios assessing PDL-1 expression. ( a ) Overall survival, and ( b ) disease-free survival in patients with hepatocellular cancer [ 21 , 22 , 23 , 24 , 25 , 26 , 28 , 30 ]. The location of the square shows the risk ratio, while the size of the square represents the individual effect of research; the black line depicts the study’s confidence interval at 95%; the edge of the diamond denotes the 95% confidence interval for the pooled hazard ratio.…”

Role of stromal PD-L1 expression in colorectal liver metastasis

“…Stromal PD-L1 expression was higher than in the primary site in patients with synchronous metastasis, but its prognostic value was not elucidated. Furthermore, one study of stromal PD-L1 expression focused on a limited number of patients with colorectal liver oligometastasis de ned as no more than ve liver metastases [20]. Therefore, we evaluated the in uence of stromal PD-L1 expression on CRLM and its prognostic value.…”