Triple negative breast cancer (TNBC) accounts for 15-20% of all breast cancers and has an increased risk of rapid metastasis within the first two years compared to other subtypes. A feature of TNBC is the high accumulation of tumour infiltrating lymphocytes (TILs) in some patients that predict a favourable prognosis and response to chemotherapy. This, along with the lack of targeted therapeutic options for TNBC, has triggered interest in trialling checkpoint-targeted immunotherapy. However, responses to date have been underwhelming are very difficult to predict, leading to an inability to accurately weigh up the benefit-to-risk ratio for their implementation. In agreement with clinical responses, our recent studies in preclinical TNBC models have demonstrated a lack of efficacy of the checkpoint inhibitor, anti-PD-1, in aggressive, immune cold TNBC tumours. Increasing the heat of the tumour via poly (I:C), a potent type I interferon inducer, sensitised mice to anti-PD-1 and induced a tumour specific T-cell response that extended metastasis-free survival. We have now built on these findings to profile the immune landscape of TNBC in a neoadjuvant sequential biopsy cohort in order to develop immune markers that predict poor chemotherapeutic response, a poor prognosis, and patients that may benefit from immunotherapeutic intervention. Utilizing multiplexed immunohistochemistry we have demonstrated that immune cell characterisation and activation status is a superior prognostic for chemotherapeutic response and risk of relapse than standard TIL score. Furthermore, we identified a novel prognostic marker that indicates presence of an intact tumour-intrinsic type I IFN signalling pathway which is superior to TIL characterisation and predicts survival in 3 independent TNBC cohorts. Our work supports preclinical and clinical trials of immunoactivating therapies in patients with IFN and immune cell cold tumours.