Exosomal PD-L1 promotes the formation of an immunosuppressive microenvironment in gastric diffuse large B-cell lymphoma

Gastric diffuse large B-cell lymphoma (GDLBCL) is a common disease with an increasing incidence. However, the regulatory effect of exosomal programmed death-ligand 1 (PD-L1) on the immune microenvironment in GDLBCL is unclear. In the present study, the protein expression levels of exosomal PD-L1 in the supernatants of cultured diffuse large B-cell lymphoma (DLBCL) cells and the plasma of patients with GDLBCL was assessed using immunoblotting. Exosomes derived from DLBCL cells were cocultured with T lymphocytes or injected into tumor xenograft mice by tail vein injection. The relationship between the protein expression level of exosomal PD-L1 in the plasma and the clinical characteristics and immune microenvironmental parameters of GDLBCL was evaluated using immunoblotting and immunohistochemistry. High levels of exosomal PD-L1 were found in the supernatants of cultured DLBCL cells. Exosomes with high levels of PD-L1 promoted growth of tumors formed by DLBCL cells in vivo and inhibited the proliferation of T lymphocytes. Notably, the protein expression level of PD-L1 in plasma exosomes derived from GDLBCL patients was significantly higher than that of healthy individuals. High levels of PD-L1 in plasma exosomes were significantly associated with international prognostic index score, pathological type and advanced Lugano stage, which might lead to the poor prognosis of GDLBCL. Moreover, a high level of PD-L1 in plasma exosomes was significantly associated with an immunosuppressive microenvironment in GDLBCL. Therefore, the results of the present study indicated that exosomal PD-L1 inhibited the proliferation of T lymphocytes and promoted the formation of an immunosuppressive microenvironment in GDLBCL. High expression of exosomal PD-L1 may suggest a poor prognosis of GDLBCL, and exosomal PD-L1 in plasma may be a new diagnostic indicator for GDLBCL.