Abstract 37P
Background
Hormone-receptor-positive breast cancer (HR+) is considered an immunologically cold cancer and has not benefited from recent advances in immunotherapy. In contrast, the triple negative breast cancer (TNBC)-subtype has demonstrated its immunogenicity through high levels of leucocytic infiltration and clinical benefits to immune checkpoint blockade. As T cells recognize antigens presented by MHC-I molecules (MAPs), we aimed to characterize the repertoire of MAPs presented in both subtypes and identify actionable targets for immunotherapy.
Methods
In 26 primary breast cancer samples (14 HR+, 12 TNBC), MAPs were identified based on a previously described proteogenomic approach (Laumont et al 2018). Essentially, MHC-I molecules are immunoprecipitated in individual tumor samples and their bound peptides are identified with mass spectrometry. The identification relies on personalized databases constructed with RNA and miRNA sequencing for each sample.
Results
We identified a total of 57 094 unique MAPs in our primary breast cancer samples. Source genes represented at the immunopeptidomic level from both canonical and non-canonical genomic origins had a very high overlap between both subtypes (>70%). We identified 25 tumor-specific antigens (TSAs; 1 mTSA and 24 aberrantly expressed TSAs), mainly originating from exonic regions of the MAGE gene family. More than 70% of our TSAs were identified from TNBC samples. In the TCGA cohort, a higher proportion of TNBC tumors express TSAs’ coding transcripts compared to HR+ tumors. Moreover, higher levels of predicted TSAs were associated to both leucocytic infiltration gene markers and higher overall survival in the TNBC cohort of TCGA, suggesting their in vivo immunogenicity. We also identified 49 tumor-associated antigens (TAAs) originating exclusively from exonic regions, including a subset deriving from cancer-associated fibroblasts.
Conclusions
Targetable antigens were identified in both subtypes of breast cancer and represent relevant new targets for cancer immunotherapy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
IRICoR.
Disclosure
All authors have declared no conflicts of interest.