The immunopeptidome landscape associated with T cell infiltration, inflammation and immune-editing in lung cancer

ABSTRACT: One key barrier to improving efficacy of personalized cancer immunotherapies that are dependent on the tumor antigenic landscape remains patient stratification. While patients with CD3+CD8+ T cell inflamed tumors typically show better response to immune checkpoint inhibitors, it is still unknown if the repertoire of HLA bound peptides presented in highly inflamed and non-inflamed tumors is substantially different. We surveyed 61 tumor regions and adjacent non-malignant lung tissues from eight lung cancer patients and performed deep antigen discovery combining immunopeptidomics, genomics, bulk and spatial transcriptomics and explored the heterogeneous expression and presentation of tumor (neo)antigens. Here we associated diverse immune cell populations with the immunopeptidome in CD3+CD8+ T cell excluded, infiltrated, highly- and lowly-inflamed tumors. We found evidence for lower immune-editing and higher presentation efficiency of tumor-associated antigens in lowly-inflamed and CD3+CD8+ T cell excluded tumors. This could have implications for the choice of combination therapies tailored to the patient’s mutanome and microenvironment.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Lung

SUBMITTER: Michal Bassani-Sternberg  

LAB HEAD: Michal Bassani-Sternberg

PROVIDER: PXD034772 | Pride | 2023-03-21

REPOSITORIES: pride