CD274 and gastric cancer: Moreover, a recent study indicated that 5-FU upregulates exosomal PD-L1 levels and leads to systemic immunosuppression in patients with advanced GC following multiple chemotherapy cycles [32] In addition to these adverse effects, the rapid emergence of resistance to 5-FU-based chemotherapy is another major clinical problem associated with the use of 5-FU [33,34].