SP5.1 Paracrine Interferon signalling between cancer associated Fibroblasts and Cancer Cells correlates with poor survival after chemotherapy in Triple Negative Breast Cancer patients
Stacey Jones- Surgery
Abstract
Aim
To determine if expression levels of Interferon-β1 (IFNβ1) in cancer associated fibroblasts, and of Myxovirus Resistance 1 (MX1) – a downstream marker of interferon activity, in cancer cells would be predictive markers of chemotherapy response and subsequent overall survival.
Methods
Breast cancer tissue was obtained from tissue microarrays of a triple negative cohort. Expression of IFNβ1 and MX1 was determined by immunohistochemistry in 109 patients treated with adjuvant chemotherapy. The cohort was further subdivided into claudin low and high subgroups, based on immunohistochemical assessment of relative expression of claudin-3.
Results
IFNβ1 in fibroblasts was significantly, positively associated with MX1 expression in tumour cells (Spearman’s correlation r=0.210; p=0.028). High expression of IFNβ1 in fibroblasts, and of MX1 in tumour cells were each significantly associated with poorer disease-free survival (p=0.01). Dividing the cohort into claudin-low (claudin-3 negative; n=49) and claudin-high (claudin-3 positive; n=60), resulted in a stronger correlation between fibroblast IFNβ1 and tumour cell MX1 in the claudin-low group (r=0.375; p=0.008), whereas it was lost in the claudin-high group (r=0.113; p=0.389). Likewise, correlations between survival and expression of IFNβ1 in fibroblasts and MX1 in tumour cells were maintained in claudin-low cases (p<0.05) but lost in claudin-highs.
Conclusion
IFNβ1 and MX1 may be of value as predictive biomarkers of chemo-response in breast cancer patients. These correlations imitate associations with chemoresistance identified in vitro using cancer associated fibroblasts and claudin-low breast cancer cell lines. Therefore, inhibiting the paracrine cross talk-between the cell types might be a viable strategy for chemo-sensitisation of breast cancers.