Abstract
BackgroundThe outcomes of immune checkpoint inhibitors in cancer patients with liver metastases are poor, which may be related to a different tumor microenvironment in liver metastases from primary tumors. This study was aimed to analyze PD-L1 expression and the immune microenvironment status in liver metastases and compare the differences of PD-L1 expression between primary tumors and liver metastases of colorectal cancer.Methods74 cases of pathologically confirmed colorectal cancer with liver metastasis underwent resection from our hospital were included. Tissue microarrays were used for the interpretation of PD-L1 expression, cluster of differentiation 4 (CD4) and CD8 density by immunohistochemistry. We evaluated the disparity between primary tumor and liver metastasis in PD-L1 expression, CD4 and CD8 density and analyzed the factors associated with obvious PD-L1 disparity.ResultsThe expression of PD-L1 was positively related to the density of CD4 and CD8 in liver metastases. The expression of PD-L1 in liver metastases was higher than in primary tumors in certain subgroups, including patients with concurrent liver metastases (n = 63, p = 0.05), patients receiving concurrent resection of primary and metastatic tumors (n = 56, p = 0.04). The two subgroups generally reflected those without inconsistent external influences, such as treatment and temporal factors, between primary tumors and liver metastases. In these subgroups, the intrinsic differences of microenvironment between primary tumors and liver metastases could be identified. Furthermore, tumor differentiation [moderate vs. poor: OR = 0.23, 95% CI: 0.03–0.99, p = 0.05)] were demonstrated to be associated with obvious discordance of PD-L1 expression between primary tumors and liver metastases.ConclusionsThe expression of PD-L1 in liver metastases was higher than in primary tumors in subgroups, reflecting intrinsic microenvironment differences between primary and metastatic tumors. Obvious discordance of PD-L1 expression between primary tumor and liver metastasis was significantly related to the tumor differentiation.
Highlights
The outcomes of immune checkpoint inhibitors in cancer patients with liver metastases are poor, which may be related to a different tumor microenvironment in liver metastases from primary tumors
Clinicopathological factors associated with PD‐L1 expression in liver metastases According to Table 1, 41 out of 74 patients (55%) were positive for Programmed cell death ligand-1 (PD-L1) expression in liver metastases; The rate of PD-L1 positivity in rectal cancer liver metastases was higher than in colon cancer liver metastases; The expression of PD-L1 in liver metastases was related to the density of cluster of differentia‐ tion 4 (CD4) and Cluster of differentiation 8 (CD8) which were higher in PD-L1 positive patients (Fig. 1). 64.3% of PD-L1-positive patients have “high” CD4 density, while there was 35.7% in PD-L1-negative patients (p = 0.05); As for high density of CD8, the proportion (94.4%) for PD-L1-positive patients was higher than
The results showed that tumor differentiation, discordance of the density of CD8 between primary tumors and liver metastases were associated with obvious discordance of PD-L1 expression between primary tumors and liver metastases
Summary
The outcomes of immune checkpoint inhibitors in cancer patients with liver metastases are poor, which may be related to a different tumor microenvironment in liver metastases from primary tumors. Wei et al J Transl Med (2020) 18:475 been shown that the patients with liver metastases benefited less from immunotherapy and may be more likely to develop new metastatic lesions compared with other metastatic lesions such as lymph node metastases and lung metastases [3]. Some researchers think this phenomenon is associated with the unique tumor microenvironment in liver metastases. It is evident that exploring the differences in the immune microenvironment between the primary tumors and liver metastases is a key point to understand the reasons for the different responses to immunotherapy
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