Abstract

Developing cancer immunotherapies relies on an accurate understanding of the diversity of cancer antigen–MHC complexes presented by immune cells, yet popular in vitro cell culture systems do not fully replicate the native tumor microenvironment. To characterize the cancer antigen fragments presented by immune cells in vivo, the authors engineered a mouse model with an affinity tag linked to the MHC heavy chain protein H2-Kb, enabling cell type-specific purification of cancer antigen–MHC complexes. In a mouse model of lung adenocarcinoma, this system revealed context-dependent changes in the peptide signatures obtained at different stages of tumorigenesis, including potential immunotherapeutic targets. Overall, this model offers a new way for the scientific community to evaluate in vivo immune cell interactions that is applicable across multiple cancer and disease settings.

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