Expression of the MHC Class II Pathway in Triple Negative Breast Cancer Tumor Cells Is Associated with a Good Prognosis and Infiltrating Lymphocytes
The MHC II pathway is usually turned off in tumor cells. Expression in triple negative breast tumors was correlated with antitumor responses and reduced relapse risk. MHC II expression may predict good prognosis, and inducing it may have therapeutic benefits. 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 x 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. (c)2016 AACR.
Cancer Immunology Research