Abstract PD1-7: Differential expression of innate and adaptive immune responses in TNBC outcome
Authors: Yesim Gokmen-Polar, Xianyin Lai, Sunil Badve
Journal: Cancer Research (2015)

Abstract Introduction: Clinical management of patients with triple-negative breast cancers (TNBCs) presents a significant challenge. TNBCs tend to relapse early and exhibit poor prognosis compared to other breast cancer subtypes. Recent studies emphasize the influence of the immune system in prognosis of TNBCs. In particular, the percentage of tumor infiltrating lymphocytes (TILs) is associated with breast cancer prognosis and outcomes after conventional therapy in triple negative tumors. However, the biology underlying this immune response is unclear. Methods: To identify differential expression of key immune response markers in TNBC with clinical outcome, we have performed a three-step approach as follows: 1) quantitative LC-MS/MS proteomic analysis using 16 formalin-fixed paraffin-embedded (FFPE) triple negative tumors with prognostic outcome and Ingenuity Pathway Analysis (IPA) performed to determine the biological processes and networks, 2) in silico analysis of prognostic value (10 year- DFMS) with the expression levels of 96 immune response genes using large cohorts of publicly available gene expression datasets (11 Affymetrix datasets), and 3) integrating the quantitative LC-MS/MS proteomic analysis with the in silico analysis to further understand the relation between the type of immune response including innate and adaptive immune responses. Results: LC-MS/MS proteomic analysis identified and quantified a total of 1,560 proteins of which 254 were differentially expressed in TNBC tumors with poor prognosis compared to good prognosis (P≤0.05). IPA analysis revealed inflammatory response and immunological processes as top differentially regulated biological functions in these tumors [P ranging between 7.41E-10 - 8.05E-03 (53 proteins) and 2.59E-09 - 5.80E-03 (69 proteins), respectively)]. The top altered immunologic networks included "Immune cell trafficking" and "cell-mediated immune response". Among the differentially regulated markers from both analyses, osteopontin (OPN or SPP1), STAT1, and MX1 remained highly significant in both proteomic and in silico analyses (P&amp;lt;0.008). Interestingly, many components of the innate immunity (i.e TLRs) and adaptive immunity (Th2 response, Th17, T-reg, T cell activation, and related cytokines) did not reach statistical significance in combinatorial analysis. Conclusion: Integrated in silico and proteomic analysis provides clues regarding the relative importance of immune pathways associated with response in breast cancer. This will enable targeting of immune therapies to improve the functionality of the pathways and ultimately in choosing the right patient TNBC subgroup for potential therapeutics, thereby improving the clinical outcome. Citation Format: Yesim Gokmen-Polar, Xianyin Lai, Sunil Badve. Differential expression of innate and adaptive immune responses in TNBC outcome [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr PD1-7.