title: Expression of the MHC Class II Pathway in Triple-Negative Breast Cancer Tumor Cells Is Associated with a Good Prognosis and Infiltrating Lymphocytes.
abstract: Triple-negative breast cancer (TNBC) is a subtype with heterogeneous patient outcomes. Approximately 40% of patients experience rapid relapse, while the remaining patients have long-term disease-free survival. To determine if there are molecular differences between primary tumors that predict prognosis, we performed RNA-seq on 47 macrodissected tumors from newly diagnosed patients with TNBC (n = 47; 22 relapse, 25 no relapse; follow-up median, 8 years; range, 2-11 years). We discovered that expression of the MHC class II (MHC II) antigen presentation pathway in tumor tissue was the most significant pathway associated with progression-free survival (HR, 0.36; log-rank P = 0.0098). The association between MHC II pathway expression and good prognosis was confirmed in a public gene expression database of 199 TNBC cases (HR, 0.28; log-rank P = 4.5 × 10(-8)). Further analysis of immunohistochemistry, laser-capture microdissected tumors, and TNBC cell lines demonstrated that tumor cells, in addition to immune cells, aberrantly express the MHC II pathway. MHC II pathway expression was also associated with B-cell and T-cell infiltration in the tumor. Together, these data support the model that aberrant expression of the MHC II pathway in TNBC tumor cells may trigger an antitumor immune response that reduces the rate of relapse and enhances progression-free survival. Cancer Immunol Res; 4(5); 390-9. ©2016 AACR.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Comprehensive Cancer Center, Birmingham, Alabama.
authors.forename: Andres
authors.initials: A
authors.lastname: Forero
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Comprehensive Cancer Center, Birmingham, Alabama.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Comprehensive Cancer Center, Birmingham, Alabama.
authors.forename: Dongquan
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Comprehensive Cancer Center, Birmingham, Alabama.
authors.forename: William E
authors.initials: WE
authors.lastname: Grizzle
authors.affiliation: Department of Oncological Sciences, University of Utah, Huntsman Cancer Institute, Salt Lake City, Utah.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Updike
authors.affiliation: Department of Oncological Sciences, University of Utah, Huntsman Cancer Institute, Salt Lake City, Utah.
authors.forename: Natalie D
authors.initials: ND
authors.lastname: Merz
authors.affiliation: Department of Pathology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.
authors.forename: Erinn
authors.initials: E
authors.lastname: Downs-Kelly
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville, Alabama.
authors.forename: Todd C
authors.initials: TC
authors.lastname: Burwell
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Comprehensive Cancer Center, Birmingham, Alabama.
authors.forename: Christos
authors.initials: C
authors.lastname: Vaklavas
authors.affiliation: Department of Radiation Oncology, University of Alabama at Birmingham, Comprehensive Cancer Center, Birmingham, Alabama.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Buchsbaum
authors.affiliation: HudsonAlpha Institute for Biotechnology, Huntsville, Alabama. Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Myers
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Comprehensive Cancer Center, Birmingham, Alabama.
authors.forename: Albert F
authors.initials: AF
authors.lastname: LoBuglio
authors.affiliation: Department of Oncological Sciences, University of Utah, Huntsman Cancer Institute, Salt Lake City, Utah.
authors.forename: Katherine E
authors.initials: KE
authors.lastname: Varley
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016000:Cluster Analysis; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006681:HLA-D Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D014407:Tumor Cells, Cultured; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D006681:HLA-D Antigens