Biomarkers of Anti-PD-L1 Response

Immune checkpoint blockers represent a breakthrough in cancer therapy, including mTNBC, yet not all patients benefit. Moreover, progression in some patients accelerates faster upon ICB administration. Therefore, there is an urgent need to identify patients who will likely to respond to ICB treatment to reduce morbidity and costs. We have completed an immunotherapy/chemotherapy trial evaluating the safety and efficacy of a combination of anti-PD-L1 (Durvalumab) and paclitaxel in patients with triple-negative breast cancer (Registered trial #NCT02628132). We hypothesized that monitoring these patients using minimally invasive procedures would provide invaluable information about the efficacy and toxicity of these agents.

In this proposal, we will measure circulating proteins, microRNAs, therapy-relevant cytokines/chemokines, and mononuclear cells from peripheral blood collected from patients receiving a combination of Durvalumab and Paclitaxel. Changes in these samples will reflect tumor biology, drug toxicity, and the patient's general condition. Changes will be investigated during chemotherapy alone, when combined with immunotherapy and when adverse effects happen. We believe this proposal will set the stage for immunotherapy monitoring of breast cancer, which will hopefully help in saving healthcare costs and, more importantly, decrease patients' suffering.