Improving assessment of immune cell infiltration in solid tumours

Using Network data to unlock the immune system’s potential to fight cancer

The immune system plays an important role in cancer prevention, destroying countless cancerous cells long before they can grow into detectable tumours. Yet some cancer cells manage to hide from immune surveillance, evolving mutations that allow them to escape detection and multiply uncontrollably until they form tumours.

Immune checkpoint therapy (ICT) can unmask these tumours, helping the immune system recognize and destroy them. First approved for clinical use in 2011, ICT has transformed cancer care for some patients, offering durable responses when traditional treatments like chemotherapy or radiation have failed. But sadly, ICT doesn’t work for everyone, and in some cases may be associated with harsh side effects.

One of the strongest predictors of ICT success is the presence of a high fraction of specific immune cells—such as B cells, T cells and Natural Killer T cells—inside the tumour. Measuring this fraction accurately is key to determining who is most likely to benefit from ICT, but we currently lack effective methods to do this.

Which is exactly why a new project led by Dr. Jennifer Chan (University of Calgary) and funded through the Marathon of Hope Cancer Centres Network is so important.

Working with Dr. Paul Gordon (University of Calgary), Dr. Chan’s team is developing VDJump, a novel software tool designed to accurately assess the composition of immune cells within a tumour using DNA data rather than the RNA data typically used today.

“RNA-based methods have been game-changers, but they’re limited by tissue type, sample handling and variable accuracy,” says Dr. Chan. “By using DNA—a far more stable molecule—we can create a tool that works across all cancer types and gives more reliable results.”

Building a better tool for precision oncology

The team will train and validate VDJump using a wealth of high-quality DNA and RNA sequencing data from the Marathon of Hope Cancer Centres Network’s Gold Cohort, which seeks to be Canada’s largest and most complete cancer case resource. The data will include cases sequenced through the Prairie Cancer Consortium (PR2C), as well hundreds of tumour cases from 13 Ontario cohorts where traditional imaging-based methods have already measured immune cell fractions.

By comparing VDJump’s DNA-based estimates to these gold-standard imaging results, the team aims to deliver a validated, published tool that clinicians and researchers can use to guide ICT decisions for cancer patients across Canada.

Importantly, because DNA sequencing is widely available and less prone to sample degradation, VDJump could be applied to existing tumour samples, helping researchers retrospectively explore links between immune cell infiltration, treatment response, and patient outcomes across many cancer types.

By enabling more accurate predictions of ICT response across all tumour types, this project represents an important step toward personalized cancer treatment—ensuring the right patients receive the right therapies at the right time.

“Our hope is that VDJump will help clinicians better match patients to treatments, improving outcomes and avoiding unnecessary side effects,” says Dr. Chan.

A pan-Canadian effort made possible by MOHCCN

Dr. Chan’s team is one of the first five teams to have access to combined data generated through the Marathon of Hope Cancer Centres Network’s Gold Cohort after being selected as a recipient of a Network Data Sharing and Use Pilot Award. This program was created to test the Network’s data sharing capacity while advancing precision oncology research for the benefit of cancer patients.

In addition to funding and access to data, the collaborative ecosystem fostered by the Network is what spurred the idea for the project in the first place, after PR2C member saw a poster from the Ontario Cancer Consortium at the 2024 TFRI Annual Scientific Meeting and recognized the potential to combine datasets and expertise.

“This project would not have come together if it were not for the MOHCCN,” says Dr. Chan. “The way the Network is structured and the funding it provides allows us to make these connections, share data and develop tools that can rapidly move from concept to reality.”