Breast cancer neoantigens can induce CD8+ T-cell responses and antitumor immunity

Xiuli Zhang, Samuel Kim, Jasreet Hundal, John M. Herndon, Shunqiang Li, Allegra A. Petti, Savas D. Soysal, Lijin Li, Mike D. McLellan, Jeremy Hoog, Tina Primeau, Nancy Myers, Tammi L. Vickery, Mark Sturmoski, Ian S. Hagemann, Chris A. Miller, Matthew J. Ellis, Elaine R. Mardis, Ted Hansen, Timothy P. FlemingS. Peter Goedegebuure, William E. Gillanders

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Next-generation sequencing technologies have provided insights into the biology and mutational landscape of cancer. Here, we evaluate the relevance of cancer neoantigens in human breast cancers. Using patient-derived xenografts from three patients with advanced breast cancer (xenografts were designated as WHIM30, WHIM35, and WHIM37), we sequenced exomes of tumor and patient-matched normal cells. We identified 2,091 (WHIM30), 354 (WHIM35), and 235 (WHIM37) nonsynonymous somatic mutations. A computational analysis identified and prioritized HLA class I-restricted candidate neoantigens expressed in the dominant tumor clone. Each candidate neoantigen was evaluated using peptide-binding assays, T-cell cultures that measure the ability of CD8+ T cells to recognize candidate neoantigens, and preclinical models in which we measured antitumor immunity. Our results demonstrate that breast cancer neoantigens can be recognized by the immune system, and that human CD8+ T cells enriched for prioritized breast cancer neoantigens were able to protect mice from tumor challenge with autologous patient-derived xenografts. We conclude that nextgeneration sequencing and epitope-prediction strategies can identify and prioritize candidate neoantigens for immune targeting in breast cancer. Cancer Immunol Res; 5(7); 516-23.

Original languageEnglish
Pages (from-to)516-523
Number of pages8
JournalCancer immunology research
Volume5
Issue number7
DOIs
StatePublished - Jul 2017

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    Zhang, X., Kim, S., Hundal, J., Herndon, J. M., Li, S., Petti, A. A., Soysal, S. D., Li, L., McLellan, M. D., Hoog, J., Primeau, T., Myers, N., Vickery, T. L., Sturmoski, M., Hagemann, I. S., Miller, C. A., Ellis, M. J., Mardis, E. R., Hansen, T., ... Gillanders, W. E. (2017). Breast cancer neoantigens can induce CD8+ T-cell responses and antitumor immunity. Cancer immunology research, 5(7), 516-523. https://doi.org/10.1158/2326-6066.CIR-16-0264