Aims:  

PD-1 and its ligands, PD-L1 and PD-L2, play an important role in tumour immune escape in a number of solid malignancies. Interaction of PD-1 on T-cells with PD-L1 on neoplastic cells results in downregulation of T-cell mediated immunity. This study aimed to contribute data on PD-1 axis expression in haematological malignancies, including plasma cell disorders (PCD), B non-Hodgkin lymphomas (B-NHL) and chronic lymphocytic leukaemias (CLL). It was hypothesised that, similarly to solid malignancies, monoclonal cells in haematological malignancy would express PD-L1/PD-L2, with a corresponding upregulation of PD-1 on T-cells.

Methods:

8-colour flow cytometry was used to investigate the expression of PD-1 and its ligands on neoplastic and normal cells. Samples consisted of peripheral blood, bone marrow, and tissue specimens obtained from 216 patients with haematological malignancy and 30 controls.

Results:

PD-L1 and PD-L2 were expressed most prominently in PCDs, with some expression in certain B-NHLs and in CLL. Expression of these ligands on monoclonal cells were increased significantly in comparison to accompanying polyclonal cells in the B-NHL and CLL groups, and was associated with PD-1 expression on T-cells. Furthermore, a subset of neoplastic cells in CLL and MM expressed PD-1.

Conclusions:

There was marked heterogeneity in the expression of the samples tested, even within the same type of malignancy, suggesting that the PD-1 axis plays a role in some, but not all, haematological malignancy cases, and may act through differing mechanisms. These findings suggest the possibility of using PD-1/PD-L1 immune checkpoint blockade as therapy in selected cases, guided by cellular expression.