Programmed death-ligand 1 (PD-L1) expression on tumor cells has been found to predict the response to immune checkpoint inhibitors in various cancers. PD-L1 is upregulated not only in tumor cells, but also in immune cells, such as macrophages in the tumor microenvironment. It is known that macrophages differentiate from monocytes. However, there are no data about PD-L1 expression in monocytes from patients with cancer. Whether PD-L1 expression on monocytes could serve as an alternative biomarker is of great interest.
We prospectively collected peripheral blood mononuclear cells from 44 untreated patients with primary breast cancer from stage I to IV between 2016 and 2018. Flow cytometry was used to detect PD-L1 expression on monocytes.
We found that the level of PD-L1 expression on monocytes increased from patients with primary breast cancer (the median of PD-L1 stained cells was 14.0% (2.6-41.2) vs. isotype control of 1.0% (0.1-11.7), p < 0.001). The median proportions of PD-L1+ monocytes in patients with stage I, II, III, and IV cancers were 7.8% (2.6-35.5), 17.9% (4.3-41.2), 16.7% (9.6-25.9), and 25%, respectively. In lymph-node metastasis negative and positive patients, the proportions were 10.9% (2.6-41.2) and 17.9% (4.3-27.3), respectively. There were no significant differences among each stage nor between groups. However, early stages of breast cancers tended to have a lower proportion of PD-L1+ monocytes. In contrast, we observed that there was no trend between PD-L1 expression and the subtypes: HR+, 17.9% (2.6-41.2); HER2+, 16.7% (7.7-25.9); or TN, 10.7% (4.3-33.2). In addition, there was no significant correlation between the proportion of PD-L1+ monocytes and Ki-67 index (p = 0.94) of tumor cells nor %tumor infiltrating lymphocytes (TILs) (p = 0.83) in primary tumors.
We found upregulated PD-L1 levels in monocytes in untreated patients with breast cancer. The proportions of PD-L1+ cells tend to increase depending on disease progression. In contrast, there was no association between PD-L1+ cells and subtypes, proliferative index, or %TILs. These data suggest that PD-L1 expression on circulating monocytes may reflect tumor burden rather than tumor biology.
Clinical trial identification
Legal entity responsible for the study
Mie University Hospital.
Has not received any funding.
All authors have declared no conflicts of interest.