People with type 2 obesity-driven diabetes tend to have more aggressive breast cancers, but no one knows exactly why. A new study by researchers at Boston University Chobanian & Avedisian School of Medicine and published in Springer Nature, found that tiny particles in the blood, known as exosomes, which are altered by diabetes, can reprogram immune cells inside the tumour, making them weaker and allowing the cancer to grow and spread more easily.
“This is the first study to directly link exosomes from people with type 2 diabetes to suppressed immune activity inside human breast tumours,” said corresponding author Gerald Denis, PhD, the Shipley Prostate Cancer Research Professor at BU.
In the study, researchers used tumour samples from breast cancer patients to grow 3D tumour models in the lab. Known as patient-derived organoids, these models contain the immune cells originally found in the tumour. These mini tumours were treated with blood exosomes from people with and without diabetes, but also without any cancer. Then, researchers analysed the organoids using single-cell RNA sequencing to see how the exosomes affected the immune cells and the tumour itself.
This is the first study to directly link exosomes from people with type 2 diabetes to suppressed immune activity inside human breast tumours. Gerald Denis, PhD
The patient-derived organoid system developed by Denis and first author Christina Ennis, PhD, is the first to preserve original immune cells from human tumours, letting scientists study tumour-immune interactions in a lab setting that closely mimics real life. In addition to breast cancer, this study may also be relevant to other cancers affected by immune suppression and metabolic disease.
“Breast cancer is already challenging to treat, and people with type 2 diabetes have worse outcomes, but clinicians don’t fully understand why,” said Denis. “Our study reveals one possible reason: diabetes changes the way the immune system works inside tumours. This could help explain why current treatments, like immunotherapy, don’t work as well in patients with diabetes. Knowing this opens the door to better, more personalized treatments for millions of people.”
Over 120 million Americans are diabetic or prediabetic, yet if they develop cancer, they are not treated differently in any significant way by the standards of treatment in oncology. Thus, this work addresses a serious public health challenge.
Source: Boston University
