ICOS+CD4+ T cells define a high susceptibility to anti-PD-1 therapy-induced lung pathogenesis.

ABSTRACT: Managing immune-related adverse events (irAEs) caused by cancer immunotherapy is essential for developing effective and safer therapies. However, cellular mechanism(s) underlying organ toxicity during anti-PD-(L)1 therapy remain unclear. Here, we investigated the effect of chronological aging on anti-PD-(L)1 therapy-induced irAE-like lung toxicity, utilizing tumor-bearing aged mice. Anti-PD-(L)1 therapy facilitated ectopic infiltration of T and B cells, and antibody deposition in lungs of aged but not young mice. Adoptive transfer of aged lung-derived CD4+ T cells into TCR-deficient mice revealed that both pathogenic CD4+ T cells and an aged host environment were necessary for the irAE-inducible responses. Single-cell transcriptomics of lung-infiltrating cells in aged mice demonstrated tha

SUBMITTER: Yokoi M 

PROVIDER: S-EPMC12128994 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature