Abstract 4862
Background
Although 5-fluorouracil chemotherapy has been thought to directly kill cancer cells and even play an immunostimulatory role, accumulating evidence indicates 5-fluorouracil also damages function of T cells through up-regulating programmed death-1-ligand 1(PD-L1), which is a negative regulator of T cell immune ability. Previous study has shown that PD-L1 has exosomal forms secreted in the microenvironment, except for membrane bound forms and extracellular soluble forms. In addition, exosomal PD-L1 retains stronger immunosuppressive activity. However, whether 5-fluorouracil can change the expression of exosomal PD-L1 and induce immunosuppression is unknown.
Methods
We retrospectively detected exosomal PD-L1, by ELISA, in 17 stage III/IV gastric cancer patients before and after 2,4,6,8 repeated cycles of 5-fluorouracil chemotherapy treatment.
Results
Compared with the expression at baseline, exosomal PD-L1 was up-regulated gradually in the plasma of patients when 2,4,6,8 repeated cycles of 5-fluorouracil were administered, accompanied with the decreased amounts of CD4+ and CD8+ T cells. Mechanistically, 5-fluorouracil up-regulated PD-L1 and exosomal PD-L1 in gastric cancer cell lines. Moreover, exosomal PD-L1 derived from gastric cancer cells induced apoptosis of T cells after 48h treatment, which could be reversed by nivolumab.
Conclusions
5-Fluorouracil up-regulated exosomal PD-L1 which induced apoptosis of T cells and caused immunosuppression in gastric cancer patients.
Clinical trial identification
Legal entity responsible for the study
Academic Group.
Funding
National Natural Science Foundation of China.
Editorial Acknowledgement
Disclosure
All authors have declared no conflicts of interest.