Ioanna Keklikoglou, University of Crete, Heraklion, Greece

Project 2023

Immune-cancer cell interactions in metastatic niches upon chemotherapy

Neoadjuvant chemotherapy (NACT) is the standard-of-care for the management of triple-negative breast cancer (TNBC), but despite its successes approximately 25% of patients with advanced disease will fail to respond or will eventually relapse, thus increasing the likelihood of metastasis. There is therefore an immediate need for alternative and improved treatment strategies. While research has largely focused on resistance mechanisms at the cancer cell level, it has become apparent that stromal microenvironment alterations are important in modulating tumour responses to therapy and in regulating metastasis formation. Our recent research has revealed that primary tumours exposed to NACT communicate with non-cancerous stromal cells at pre-metastatic niches through the release of pro-metastatic extracellular vesicles (EVs), thus limiting the therapeutic efficacy of NACT. The goal of this proposal is to reveal how NACT modifies the immune landscape in the metastatic niche, and to discover the immune subsets modulating therapy-induced metastasis during the different stages of the metastatic process. Using single-cell transcriptomics, computational as well as in vivo and in vitro approaches, we aim to identify distinct myeloid-derived sub-populations that could be therapeutically exploited to improve chemotherapeutic responses of patients with metastatic disease, thus providing the basis for translating this work into an improved treatment for TNBC.