Targeting CD39 boosts PD-1 blockade antitumor therapeutic efficacy via strengthening CD8 + TILs function and recruiting B cells in cervical cancer.

Abstract

Although the programmed cell death protein 1 (PD-1) blockade has been authorized for the treatment of recurrent and metastatic cervical cancer (CC) patients, a significant proportion of CC patients show low objective response rates (ORR) to immune checkpoint blockades (ICBs). Therefore, identifying novel combination treatment strategies to enhance ICBs therapeutic efficacy for CC patients is urgently needed. Here, we discovered that CD39 was highly expressed in exhausted CD8 + T cells from 10 CC patients in our center via single-cell RNA sequencing (scRNA-seq). Furthermore, we validated that CC patients with CD39 highly expressed in CD8 + T cells associated with poor prognosis and immunoevasive subtype of CC both in cohort from our center and the Cancer Genome Atlas (TCGA) database. Moreover, it was also confirmed that CD39-inhibiting not only enhanced the cytotoxicity of CD8 + tumor-infiltrating lymphocytes (TILs) but also promoted the infiltration of B cells through increasing CXCL13 secretion both in vitro experiments and subcutaneous tumor models, thereby amplifying anti-tumor immunity of PD-1 blockade. What was more, we have developed a liposome containing POM-1, which effectively enhanced the anti-tumor effect of POM-1. Our findings provide compelling evidence that targeting CD39 represents a promising "two birds with one stone" strategy for cervical cancer treatment.