PD-L1 expression in liver metastasis: its clinical significance and discordance with primary tumor in colorectal cancer

Abstract

Background 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. 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. Methods 74 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. Results The 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. Conclusions The 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.

Liver Immune Microenvironment and Metastasis from Colorectal Cancer-Pathogenesis and Therapeutic Perspectives

“…However, this mechanism is utilized by cancers to escape from anti-tumor immunity. Previous study showed that the expression of PD-L1 was increased in liver metastases compared to primary CRC, indicating different intrinsic microenvironment between primary and metastatic CRC [ 110 ], which may help CRC liver metastases escape from immune surveillance. In addition, it was reported that chemotherapy can modulate PD-L1 and TIM-3 expression in CRC liver metastases, suggesting the potential strategy of combined chemo-immunotherapies [ 111 ].…”

Antitumor Effects of Ursolic Acid through Mediating the Inhibition of STAT3/PD-L1 Signaling in Non-Small Cell Lung Cancer Cells

“…Some studies showed that high PD-L1 expression was associated with tumor metastasis, cancer recurrence, and tumor invasion; PD-L1 could be considered an independent element in evaluating immunotherapy during metastasis [ 27 , 28 ]. As such, PD-L1 could play a crucial role in the immune microenvironment between the primary tumor and the secondary metastatic tumor; PD-L1 can help increase the understanding of cancer’s response to immunotherapy and develop PD-L-targeted therapy [ 29 ].…”

The clinicopathological significance and predictive value for immunotherapy of programmed death ligand-1 expression in Epstein-Barr virus-associated gastric cancer

“…Immunohistochemistry staining of tissue sections was performed as described previously. 23 An antihuman PD-L1 monoclonal antibody (E1L3N, Cell Signaling Technology) was used per the manufacturer’s instructions. PD-L1 expression was evaluated using the scoring method of the combined positive score (CPS), which is the number of positive cells (tumor cells, lymphocytes, and macrophages)/the total number of viable tumor cells, and multiplied by 100.…”