CD22 特异性嵌合抗原受体修饰 T 细胞上程序性死亡配体 1 的表达削弱抗肿瘤潜能

The molecules of programmed cell death protein-1 (PD-1) and ligand-1 (PD-L1) become new therapeutic targets for cancer therapy. Although tumor-expressed PD-L1 molecule is frequently dispensable for checkpoint blockade in some cancer patients, recent studies suggest that T cell-expressed PD-L1 molecule might play a crucial role in antitumor immunity.

Here, to investigate CD22 chimeric antigen receptor (CAR)-T cell therapy, we have generated the different CD22 CAR-T constructs.

We noticed that tumor cells induced PD-L1 expression on the surface of CD22 CAR-T cells. The induced PD-L1 might limit immunogenic responses of CAR-T cells. T cell-expressed PD-L1 leads to a suppressive signal by PD-1/PD-L1 engagement of CD22 CAR-T cells. Meanwhile, PD-L1 suppresses CD22 CAR-T cell differentiation into memory T cells and negatively affected secretions of several essential cytokines, such as interleukin-2 (IL-2) and tumor necrosis factor (TNF)- .

We further observed that anti-PD-L1 monoclonal antibodies rescued cytokine secretion of CD22 CAR-T cells rather than anti-PD-1 monoclonal antibodies.

Our current studies provide a potential mechanism to understand the functions and roles of T cell-expressed PD-L1 in tumor microenvironment. These results will encourage the physicians to re-recognize the important roles of PD-L1 in cancer immunotherapy studies and provide the helpful guidance for clinical operation of PD-L1 inhibition drugs.