MO5-2 Cabozantinib may enhance efficacy of anti-PD-1 therapy in hepatocellular carcinoma through suppression of MDSCs

Translational research on drug development and biomarker discovery for hepatocellular carcinoma

“…Lenvatinib may inhibit the PKCα/ZFP64/CSF1 [146] and transforming growth factor-β signaling pathways in the TME of HCC (Table 4) [152]. Cabozantinib may also increase neutrophil chemotaxis, induce infiltration of TANs [153] with a more cytotoxic N1 phenotype [154], and reduce intra-tumoral myeloid-derived suppressor cells (MDSCs) (Table 4) [155]. Although these immunomodulatory mechanisms of MKIs may enhance effector T-cell infiltration and response to anti-PD1 therapy in preclinical HCC models, the lack of additional survival benefits provided by combination therapy in randomized clinical trials indicates that additional comprehensive mechanistic studies are required to determine whether and how these mechanisms enhance antitumor immunity in clinical settings.…”