Trilaciclib triggers a neutrophil-related immune response and sensitizes non-small cell lung cancer to anti-PD-1 therapy (PRJCA043311)

Trilaciclib is a cyclin-dependent kinase 4/6 inhibitor approved for myelopreservation in extensive-stage small cell lung cancer. Our results demonstrate that trilaciclib reprogrammed the tumor immune microenvironment by primarily increasing the proportion of antitumor neutrophils and CD8+T cells. Trilaciclib induces tumor cell senescence and the senescence-associated secretory phenotype in a cGAS-STING-dependent manner, which further facilitates the infiltration and activation of CD177+ neutrophils with anti-tumor properties. The CD177+ neutrophils promote CD8+ effector T cell activation and induce CD8+ T cell-mediated antitumor immunity. Combining trilaciclib with an anti-PD-1 antibody may be a promising combination strategy for NSCLC treatment.