Mikael Olefs

Immunotherapy has improved outcomes for several cancer types, but its effectiveness in estrogen receptor-positive (ER+) breast cancer remains limited. A major reason is the low immune visibility of these tumors. This project investigates a mechanism that allows ER+ breast cancer cells to avoid immune activation and explores how interfering with this process could improve responses to immunotherapy.
Cancer cells release extracellular vesicles (EVs), small membrane-bound particles that help maintain cellular balance by removing unwanted material, including damaged DNA. By exporting cytoplasmic DNA, EVs prevent activation of the cGAS-STING pathway, an important innate immune signaling system that promotes anti-tumor immunity. The small GTPase Rab27b, a key regulator of EV release, is highly active in invasive ER+ breast cancer and is associated with poor patient prognosis.
Disruption of Rab27b function, or its interaction with the effector protein melanophilin, reduces EV-mediated DNA secretion. This leads to cytosolic DNA accumulation, activation of DNA damage response pathways, and stimulation of cGAS-STING signaling, resulting in decreased cancer cell survival and enhanced immune activation.
My project aims to define how Rab27b-driven EV release influences tumor progression and immune escape. Ultimately, this work seeks to establish Rab27b as a therapeutic target to sensitize ER+ breast cancers to immune checkpoint therapies while limiting systemic toxicity.
 

• 2016-2020: Bachelor of Biochemistry (University of Victoria, Canada)
• 2022-2024: Master of Molecular Biology (Vrije Universiteit Brussel)
• 2025-Present: PhD student, Laboratory of Experimental Cancer Research
   

• Lab address: 
  Laboratory of Experimental Cancer Research, 
  Department of Human Structure and Repair, 
  Campus UZ Gent, Corneel Heymanslaan 10, The Core, entrance 37, 9000 Gent, Belgium
• Mikael Olefs is interested to receive invitations for presentations or talks