Antigen presentation; Breast cancer; Cancer immunotherapy; Immunology; Oncology; Antigens, Neoplasm; Humans; Antigens, Neoplasm/genetics; Immunotherapy/methods; CD8-Positive T-Lymphocytes/pathology; Triple Negative Breast Neoplasms/pathology; General Medicine
Abstract :
[en] Hormone receptor-positive breast cancer (HR+) is immunologically cold and has not benefited from advances in immunotherapy. In contrast, subsets of triple-negative breast cancer (TNBC) display high leukocytic infiltration and respond to checkpoint blockade. CD8+ T cells, the main effectors of anticancer responses, recognize MHC I-associated peptides (MAPs). Our work aimed to characterize the repertoire of MAPs presented by HR+ and TNBC tumors. Using mass spectrometry, we identified 57,094 unique MAPs in 26 primary breast cancer samples. MAP source genes highly overlapped between both subtypes. We identified 25 tumor-specific antigens (TSAs) mainly deriving from aberrantly expressed regions. TSAs were most frequently identified in TNBC samples and were more shared among The Cancer Genome Atlas (TCGA) database TNBC than HR+ samples. In the TNBC cohort, the predicted number of TSAs positively correlated with leukocytic infiltration and overall survival, supporting their immunogenicity in vivo. We detected 49 tumor-associated antigens (TAAs), some of which derived from cancer-associated fibroblasts. Functional expansion of specific T cell assays confirmed the in vitro immunogenicity of several TSAs and TAAs. Our study identified attractive targets for cancer immunotherapy in both breast cancer subtypes. The higher prevalence of TSAs in TNBC tumors provides a rationale for their responsiveness to checkpoint blockade.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Kina, Eralda ; Institute for Research in Immunology and Cancer (IRIC), and ; Department of Medicine, University of Montreal, Montreal, Quebec, Canada
Laverdure, Jean-Philippe; Institute for Research in Immunology and Cancer (IRIC), and
Durette, Chantal; Institute for Research in Immunology and Cancer (IRIC), and
Lanoix, Joël; Institute for Research in Immunology and Cancer (IRIC), and
Courcelles, Mathieu; Institute for Research in Immunology and Cancer (IRIC), and
Zhao, Qingchuan; Institute for Research in Immunology and Cancer (IRIC), and ; Department of Medicine, University of Montreal, Montreal, Quebec, Canada
Apavaloaei, Anca; Institute for Research in Immunology and Cancer (IRIC), and ; Department of Medicine, University of Montreal, Montreal, Quebec, Canada
Larouche, Jean-David; Institute for Research in Immunology and Cancer (IRIC), and ; Department of Medicine, University of Montreal, Montreal, Quebec, Canada
Hardy, Marie-Pierre; Institute for Research in Immunology and Cancer (IRIC), and
Vincent, Krystel; Institute for Research in Immunology and Cancer (IRIC), and
Gendron, Patrick; Institute for Research in Immunology and Cancer (IRIC), and
Hesnard, Leslie ; Institute for Research in Immunology and Cancer (IRIC), and
Thériault, Catherine; Institute for Research in Immunology and Cancer (IRIC), and
Ruiz Cuevas, Maria Virginia; Institute for Research in Immunology and Cancer (IRIC), and ; Department of Medicine, University of Montreal, Montreal, Quebec, Canada
Ehx, Grégory ; Université de Liège - ULiège > Département des sciences cliniques
Thibault, Pierre ; Institute for Research in Immunology and Cancer (IRIC), and ; Department of Chemistry, University of Montreal, Montreal, Quebec, Canada
Perreault, Claude ; Institute for Research in Immunology and Cancer (IRIC), and ; Department of Medicine, University of Montreal, Montreal, Quebec, Canada
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