by University of Leicester

Maintenance of the immune microenvironment in BC-PDEs. Whole slide mIF-stained sections of BC-PDEs were digitized using a Vectra Polaris and analyzed in InForm. (A) Representative image of a single PDE stained for CD4, CD8, FOXP3, CK and DAPI. (B) Individual cells were phenotyped into T-Helper (CD4 + ve), T-effector (CD8 + ve), T-regulatory (CD4 + ve FOXP3 + ve), Tumor cells (CK + ve) negative (DAPI + ve). (C) There was no significant difference in cell density/mm2 for T-regulatory, T-effector and T-helper cells in both tumor and stroma in uncultured (48 BC-PDEs) compared to vehicle control (52 BC-PDEs) treated BC-PDEs using Mann–Whitney test, where p < 0.05 (indicated by *) was considered significant. (D) Example image of functional inter-cell distance calculation showing Distance from T-effector to CK cells. Scale bars represent 200 µm. Credit: Scientific Reports (2024). DOI: 10.1038/s41598-024-63170-0

Cancer researchers at the University of Leicester have developed a technique that could predict how well some breast cancer patients will respond to chemotherapy and antibody-directed cancer treatments.

The evaluation of the patient derived explant (PDE) technique has been published in Scientific Reports.

Among women, breast cancer is the most common global cancer, with 2.3 million cases diagnosed annually. Despite significant advances in early diagnosis and treatments for breast cancer, 670,000 women still die around the world every year (WHO 2022 data).

In this study, researchers implemented cutting-edge digital pathology and multi-immunofluorescent techniques to investigate changes in samples of patient tumors in a laboratory.

Gareth Miles, Lecturer in Cancer Patient Derived Explant Technology at the University of Leicester, said, “In the era of personalized medicine, specific targeted therapies now exist for the different types of breast cancer. Despite these tremendous successes, there are a number of tumors that remain difficult to treat.

“Historically, it’s been very difficult to understand how well some patients’ tumors will respond to the treatments that are available. This means some patients have to go through unpleasant treatments that sadly don’t work. Developing a more accurate method of testing in the lab helps doctors to improve clinical outcomes.”

In their previous work on non-small cell lung cancer and endometrial cancer patient derived explants (PDEs) the University of Leicester team observed a significant relationship with explant responses to chemotherapy drugs and patient outcomes. This paved the way for the latest research.

In the latest study, the team measured the stability of 55 breast cancer patients’ tumor “explants” over time. They “treated” the tumor explant with either chemotherapy or HER2 antibody therapy trastuzumab in the lab.

Professor Catrin Pritchard, Professor of Cancer Biochemistry at the University of Leicester, added, “Importantly, our data showed that using our method the architecture of the tumor was maintained for up to 72 hours during testing and the immune microenvironment was preserved. This is highly encouraging as it’s something that other testing techniques have struggled with. It gives us confidence that the testing we did on this sample was meaningful.

“We then compared our observations of the tumor explant as it underwent ‘treatment’ in the lab to what we knew about each breast cancer patient’s progression as they underwent their clinical treatment. We found a similar pattern in responsiveness in the patient’s explant to their clinical progression.

“This is particularly encouraging as it suggests the tumor explant in the lab was responding in the same way the tumor did in the patient.

“Our findings suggest that our patient derived explant technique could be a suitable preclinical testing platform for some breast cancer patients.

“It could provide a more accurate method to predict how they may respond to particular treatments. Doctors can avoid giving ineffective treatments, saving time and ultimately improving a patient’s clinical outcome.”

More information: Constantinos Demetriou et al, An optimised patient-derived explant platform for breast cancer reflects clinical responses to chemotherapy and antibody-directed therapy, Scientific Reports (2024). DOI: 10.1038/s41598-024-63170-0

Journal information:Scientific Reports

Provided by University of Leicester

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