3.1CD39 mAb combined with PD-1 mAb
PD-1 is a gene encoding immunoglobulin superfamily proteins, is focused
on sustaining immune tolerance to autoantigens and preventing autoimmune
diseases. PD-L1 is a ligand of PD-1. Blocking the interaction between
tumor cells expressing PD-L1 and tumor-specific T cells expressing PD-1
using PD-1 or PD-L1 antibodies enhances T cells cytolytic
activity[21].It has strong therapeutic value and significance in
solid tumor and hematologic malignancy[29, 55].However, during
immunotherapy of tumors, many tumors show resistance to PD-1/PD-L1. One
reason many patients exhibit resistance may be due to the
immunosuppressive TME, where ROS or nitrogen oxides (NO) released by
bone marrow-derived suppressor cells (MDSC) tire T cells and NO longer
recognize tumor cells. PD1 resistance and poor prognosis in
hepatocellular carcinoma (HCC) patients are associated with
up-regulation of CD39 expression in macrophages, and CD39 can be used as
a marker of unfavorable prognosis in HCC patients[33].Combination
therapy with CD39 mAb significantly improved this situation. It is
reported that the therapy combining anti-CD39 and anti-PD1 mAb can
further slow tumor growth, and inhibition of CD39 enzyme function can
make the tumor model with inherent drug resistance sensitive to PD1
antibody[10, 34].This may be because CD39 mAb and PD-1 mAb could
recover the ability of CD8+T cells to produce cytokines. CD39 mAb
combined with PD-1 mAb has become one of the targets of many tumor
therapies[33].