Systems Profiling Reveals Recurrently Dysregulated Cytokine Signaling Responses in ER+ Breast Cancer Patients' Blood

Overview

Journal bioRxiv

Date 2023 Nov 14

PMID 37961682

Authors

Brian Orcutt-Jahns

Joao Rodrigues Lima Junior

Russell C Rockne

Adina Matache

Sergio Branciamore

Ethan Hung

Andrei S Rodin

Peter P Lee

Aaron S Meyer

Affiliations

Soon will be listed here.

Abstract

Cytokines mediate cell-to-cell communication across the immune system and therefore are critical to immunosurveillance in cancer and other diseases. Several cytokines show dysregulated abundance or signaling responses in breast cancer, associated with the disease and differences in survival and progression. Cytokines operate in a coordinated manner to affect immune surveillance and regulate one another, necessitating a systems approach for a complete picture of this dysregulation. Here, we profiled cytokine signaling responses of peripheral immune cells from breast cancer patients as compared to healthy controls in a multidimensional manner across ligands, cell populations, and responsive pathways. We find alterations in cytokine responsiveness across pathways and cell types that are best defined by integrated signatures across dimensions. Alterations in the abundance of a cytokine's cognate receptor do not explain differences in responsiveness. Rather, alterations in baseline signaling and receptor abundance suggesting immune cell reprogramming are associated with altered responses. These integrated features suggest a global reprogramming of immune cell communication in breast cancer.

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