Relapse or Eradication of Cancer Is Predicted by Peptide-Major Histocompatibility Complex Affinity

SummaryCancers often relapse after adoptive therapy, even though specific T cells kill cells from the same cancer efficiently in vitro. We found that tumor eradication by T cells required high affinities of the targeted peptides for major histocompatibility complex (MHC) class I. Affinities of at least 10 nM were required for relapse-free regression. Only high-affinity peptide-MHC interactions led to efficient cross-presentation of antigen, thereby stimulating cognate T cells to secrete cytokines. These findings highlight the importance of targeting peptides with high affinity for MHC class I when designing T cell-based immunotherapy.

► Tumor relapse versus eradication is determined by affinity of peptide for MHC.
► Outcome of adoptive T cell therapy is determined by affinity of peptide for MHC.
► Stroma is only destroyed in tumors expressing peptides with high affinity for MHC.
► Efficient cross-presentation is dependent on high peptide-MHC affinity