Molecular signatures mostly associated with NK cells are predictive of relapse free survival in breast cancer patients

Abstract

BackgroundRecent observations suggest that immune-mediated tissue destruction is dependent upon coordinate activation of immune genes expressed by cells of the innate and adaptive immune systems.MethodsHere, we performed a retrospective pilot study to investigate whether the coordinate expression of molecular signature mostly associated with NK cells could be used to segregate breast cancer patients into relapse and relapse-free outcomes.ResultsBy analyzing primary breast cancer specimens derived from patients who experienced either 58–116 months (~5-9 years) relapse-free survival or developed tumor relapse within 9–76 months (~1-6 years) we found that the expression of molecules involved in activating signaling of NK cells and in NK cells: target interaction is increased in patients with favorable prognosis.ConclusionsThe parameters identified in this study, together with the prognostic signature previously reported by our group, highlight the cooperation between the innate and adaptive immune components within the tumor microenvironment.

DNA methyltransferase inhibition increases efficacy of adoptive cellular immunotherapy of murine breast cancer

“…To normalize for the amount of source RNA, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) transcripts from the same samples were measured and used as internal reference. Transcript expression was validated using the comparative C t method for relative quantification ( ΔΔ C t ) referenced to the amount of a common reference gene (GAPDH), as previously described [30]. …”

Establishment of a heterotypic 3D culture system to evaluate the interaction of TREG lymphocytes and NK cells with breast cancer

“…Alterations in NK cell phenotype and functionality are dependent on tumour stage and presentation, with NK cells exhibiting poor cytotoxic capacity dominating NK populations in advanced breast cancer immune infiltrates (Dewan et al, 2009;Mamessier et al, 2011Mamessier et al, , 2013. The prognostic significance of NK cells in breast cancer has yet to be established (Roberti et al, 2012), however, gene expression studies have indicated that signatures associated with NK cells are predicative of relapse free-survival in primary breast cancer patients (Ascierto et al, 2013). The scarcity of NK cells and the dominance of T REG lymphocytes in advanced TIL populations may be linked to breast cancer immune evasion and tumour tolerance strategies, where the induction of a local inflammatory response is employed for tumour progression.…”

Guanylate-Binding Protein-1 protects ovarian cancer cell lines but not breast cancer cell lines from killing by paclitaxel

“…Elevated hGBP-1 also shortens progression-free survival (PFS) in patients with ovarian cancer (Wadi et al, under review). However, hGBP-1 is part of a 5-gene signature correlated with improved PFS for all subclasses of breast cancer [5]. Since paclitaxel is part of the standard treatment of breast cancer patients who receive chemotherapy, the possibility that hGBP-1 promotes paclitaxel resistance is inconsistent with its correlation with improved prognosis.…”

“…An the other hand, hGBP-1 inhibits proliferation and invasion of endothelial cells by down-regulating MMP-1 expression [10,11], thereby inhibiting angiogenesis. Its expression is correlated with improved RFS in both colon and breast cancers [5,12]. Much remains unclear about how hGBP-1 functions and it is still unknown how it contributes to such effects on prognosis in the different tumor types.…”