Enhancement of immune checkpoint inhibitor efficacy by DHX58+ SELL+ T cells in advanced gastric cancer

Abstract Although there have been recent advancements in immune checkpoint inhibitors (ICIs) for gastric cancer (GC), pinpointing the essential T‐cell subsets that drive antitumor responses continues to pose a challenge. In this study, we created a coculture system using patient‐derived organoids (PDOs) and tumor‐infiltrating lymphocytes (TILs) that mimics important interactions between PDOs and TILs in the presence of various ICIs. Our findings reveal that CD62L+ T cells, activated by CD44+ cancer stem cells (CSCs), facilitate tumor regression in samples sensitive to ICIs. Additionally, publicly available single‐cell RNA sequencing (scRNA‐seq) data indicate that stem‐like SELL+ T cells, which show increased expression of DHX58, enhance their interactions with CD44+ CSCs in GC patients who have favorable prognoses. This research highlights the promise of DHX58+ SELL+ T cells, in a stem‐like state prompted by CD44+ CSCs, as potential diagnostic markers and targets for T cell‐based immunotherapy in GC.