Abstract PO005: Hepatic stellate cells suppress NK cell sustained breast cancer dormancy

Abstract

Abstract The persistence of undetectable disseminated tumour cells (DTCs) after primary tumour resection poses a major challenge to effective cancer treatment. These enduring dormant DTCs are seeds of future metastases, and the mechanisms that switch them from dormancy to outgrowth require definition. Because cancer dormancy provides a singular therapeutic window to prevent metastatic disease, a comprehensive understanding of the distribution, composition and dynamics of dormant DTC reservoirs is imperative. Here we reveal tissue-specific microenvironments that restrain or concede progression of breast cancer in the liver, a frequent site of metastasis and most times associated with patients’ cause of death. Using mouse models, we show that the dormant milieu features a selective accumulation of natural killer (NK) cells. Preserving the NK cell pool with adjuvant interleukin-15-based immunotherapy prevents hepatic metastases and prolongs survival. Exit from dormancy follows a dramatic contraction of the NK cell compartment, and concurrent accumulation of activated stellate cells. Our data identify the interplay between NK cells and activated stellate cells as a master switch of cancer dormancy, and suggest that therapies aimed at normalizing the NK cell pool might succeed in preventing DTC outgrowth and metastasis. Citation Format: Ana Luisa Correia. Hepatic stellate cells suppress NK cell sustained breast cancer dormancy [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr PO005.