Abstract P1-07-06: Immune signatures define and affect prognosis in triple-negative breast cancer subtypes

Abstract

Abstract Background: The tumor immune microenvironment is formed by many distinct and interacting cell populations, and its composition may predict patient's prognosis and response to therapies. Triple negative breast cancer (TNBC) is a heterogeneous disease in which different genomic subgroups have been described (Lehmann, et al. J Clin Invest.2011). Our aim was to integrate the composition of the tumor immune microenvironment with the molecular TNBC subtypes. Methods: We retrospectively analyzed the composition and the functional orientation of the immune microenvironment of 963 TNBC tumors clustered in 4 main TNBC subgroups (Basal-Like [BL1/2], Immunomodulatory [IM], Mesenchymal/Mesenchymal Stem-Like [MS], Androgen Receptor [AR]) from independent cohorts using transcriptomic profiling. TNBC were stratified based on 9 different immune signatures (Natural Killer [NK], Dendritic Cells [DC], T-Cells [TC], B-Cells [BC], T-Cytotoxic [TC], Interferon [IF], Nuclear Factor-kB [NF-kB], anti-tumor Macrophages [M1] and pro-tumor Macrophages [M2]. We validated our findings using immunohistochemistry. Results: We report that TNBC molecular subgroups and specific microenvironmental immune signatures are highly correlated. The IM was enriched of almost all the immune modules. On overall TNBC population, the TC (P = 0.01), IF (P = 0.007) and M1 (P = 0.001) signatures were associated with good prognosis. The BL subgroup with a good prognosis was characterized by overexpression of genes specific to M1-macrophages (P = 0.004) and TC-lymphocytes (P = 0.01). In contrast, the poor-prognosis MS expresses markers of cells of monocytic origin and significantly associated with the M2 signature (P = 0.01). The MS subgroup also displays an inflammatory and immunosuppressive signature. Pathological examination revealed that the MS subtype is characterized by a high density of pro-tumor macrophages that likely produce chemokines and cytokines which favor tumor-associated inflammation, resulting in a poor prognosis. In contrast, the AR exhibits low immune and inflammatory signatures. Conclusions: The distinct immune orientations of the TNBC molecular subtypes pave the way for tailored immunotherapies. Citation Format: Bottai G, Balazs G, Nagy A, Pusztai L, Szallasi Z, Reis-Filho JS, Santarpia L. Immune signatures define and affect prognosis in triple-negative breast cancer subtypes [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-07-06.