Given that APC activation via CD40-CD40L-mediated non-canonical NF-κB pathway is essential for the antitumor effects of ICI therapy, and the gut microbiota can impact the treatment outcome of anti-CD40 immunotherapy,56,76 the strong Cd40-Cd40l interaction and enrichment of non-canonical NF-κB pathway in the PW groups, as well as tumor-infiltrating APCs activation induced by CD40 agonists, suggest that gut microbiota may enhance the ICI treatment outcome via Cd40l-Cd40 mediated γδ T cell-APC activation and subsequent CD86-CD28 mediated APC-CD8+ T cell activation. The gene discussed is CD28; the disease is neoplasm.