CLL is an incurable low-grade malignant type of B cell non-Hodgkin lymphomas. Recently, CLL patients developed resistance towards the existing therapeutic agent such as ibrutinib, which inhibits the B cell receptor (BCR) signaling. Our laboratory could show that treatment with BCR inhibitors could inhibit the expression of the immune checkpoint ligand PD-L1 on CLL cells. Besides, BCR signaling was found to influence the release of extracellular vesicles (EV), which also express PD-L1. Interestingly, PD-L1 expression on CLL-derived EVs was also inhibited by ibrutinib.
Based on these preliminary results, I will investigate the potential regulation of PD-L1 by the BCR signaling pathway on CLL-cells and CLL-derived EVs, on a molecular level. My aims include detection of EV-mediated transfer of PD-L1 and modifications of PD-L1 expression on CLL-derived EV after BCR knockout and inhibition. The project may provide new insights into the combinatory effect of BCR inhibition and immune therapy in CLL.