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1411 Breast cancer immunopeptidomes contain numerous shared tumor antigens
  1. Eralda Kina1,
  2. Jean-Philippe Laverdure1,
  3. Chantal Durette1,
  4. Joël Lanoix1,
  5. Mathieu Courcelles1,
  6. Qingchuan Zhao1,
  7. Anca Apavaloaei1,
  8. Jean-David Larouche1,
  9. Marie-Pierre Hardy1,
  10. Krystel Vincent1,
  11. Patrick Gendron1,
  12. Leslie Hesnard1,
  13. Maria Virginia Ruiz Cuevas1,
  14. Gregory Ehx2,
  15. Pierre Thibault1 and
  16. Claude Perreault1
  1. 1University of Montreal, Montreal, Canada
  2. 2University of Liege, Liege, Belgium


Background Hormone-receptor-positive breast cancer (HR+) is an immunologically cold cancer that has not benefited from advances in immunotherapy. In contrast, triple-negative breast cancer (TNBC) displays high levels of leukocytic infiltration and responds to immune checkpoint inhibitors. CD8 T cells, the main effectors of anti-cancer responses, recognize MHC I-associated peptides (MAPs). Our work aimed to characterize the repertoire of MAPs presented by HR+ and TNBC tumors.

Methods Using a proteogenomic approach relying on mass spectrometry, we identified 57 094 unique MAPs in 26 primary breast cancer samples (14 HR+, 12 TNBC).

Results MAP source genes showed a high overlap between both subtypes (>70%). We identified 25 tumor-specific antigens (TSAs) derived from various genomic regions, of which 24 were unmutated. TSAs were mainly identified in TNBC samples (70%) and were more highly shared among TCGA TNBC than HR+ samples. In the TNBC TCGA cohort, the predicted number of TSAs positively correlated with leukocytic infiltration (p<0.05) and overall survival (p<0.05, figure 1), suggesting that these TSAs are immunogenic in vivo. We also identified 49 overexpressed tumor-associated antigens (TAAs), some of which derived from cancer-associated fibroblasts. FEST assays confirmed the in vitro immunogenicity of our TSAs and TAAs.

Conclusions Well-defined antigens were identified in both subtypes of breast cancer and represent attractive targets for cancer immunotherapy. The higher prevalence and immunogenicity of TSAs in TNBC tumors provide a molecular rationale for the responsiveness of TNBC to immune checkpoint inhibitors.

Ethics Approval Approved by the comity for clinical research of University of Montreal (CERC-20-012-D)

Abstract 1411 Figure 1

Aberrantly expressed TSAs predicted presentation confers a survival advantage to patients with TNBC tumors

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