Immunosuppressive profiles in liquid biopsy at diagnosis predict response to neoadjuvant chemotherapy in triple-negative breast cancer

• DOI: 10.1016/j.ejca.2020.08.020
• Publication Date: 2020-09-29T10:21:59Z
• Authors: Carmen Salvador-C...; Ana Santaballa; Elena Sanmartín; David Calvo; Ana García; David Hervás; Lourdes Cordón; Guillermo Quintas; Francisco Ripoll; Joaquín Panadero; Jaime Font de Mora
• Keywords: Neoadjuvant Therapy; Liquid biopsy; Complete response; Triple negative

Triple-negative breast cancer (TNBC) is characterised by high pathological complete response to neoadjuvant chemotherapy (NAC). However, refractory and poor NAC responders still face very outcome, emphasising the urgent need for tools that facilitate identification of these patients, so surgery or alternatives are considered early in treatment protocol.We combined metabolomics, exosome circulating miRNAs flow cytometry experimental approaches TNBC patients at diagnosis with immunohistochemistry needle biopsy tumours generate NAC-response predictive models. We also co-cultured studied crosstalk between isolated patient-derived myeloid-derived suppressor cells (eMDSCs) cell lines.Blood-derived liquid biomarkers display a novel immunosuppressive profile tryptophan-derived metabolites eMDSC levels significantly predict response. Notably, indoleamine 2,3-dioxygenase 1 (IDO1) expression tumour inversely correlated tryptophan but directly level eMDSCs. In addition, set target pathways immune maturation predicted prior chemotherapy. Interestingly, IDO1 increased when lines were eMDSCs this, turn, promoted proliferation eMDSCs.Our findings demonstrate suppressive system play key role modulating TNBC. identify mechanism exacerbates immunosuppression. These results provide potential new tool alternative strategies treatment, including surgical resection tumour, explore them therapies.