L-Tetrahydropalmatine synergizes cytotoxic CD8(+) T mediated antitumor and ferroptosis in gastric cancer.

L-Tetrahydropalmatine (L-THP) is an isoquinoline alkaloid derived from the traditional Chinese herb Corydalis (genus Corydalis), particularly its analgesic and sedative effects. The in-depth function of L-THP on gastric cancer (GC) immune escape is still unclear. Here, the present research aimed to investigate the function of L-THP on GC antitumor response. Results indicated that L-THP promoted the cytotoxicity and antitumor response of CD8(+) T cells to GC cells. Moreover, L-THP up-regulated the ferroptosis of GC cells. Mechanistically, L-THP recognized the FSP1 protein and bound to FSP1 with high binding affinity. L-THP reduced the FSP1 stability to trigger the ferroptosis of GC cells. In conclusion, this study shows that L-THP synergizes cytotoxic CD8(+) T cell-mediated GC antitumor response and ferroptosis through FSP1, providing potent evidence for GC immunoregulation.