Think of a tumor as a busy neighborhood where cancerous and non-cancerous cells constantly interact. Similar to neighborhoods that vary in architecture, tumors are marked by heterogeneity, which makes treatment particularly challenging. This complexity includes different cell types; immune cells trying to fight the tumor and the actual tumor cells themselves. Thanks to recent advances in imaging technology, scientists can now capture and study this heterogeneity in unprecedented detail.
New cancer therapies rely on the immune system’s natural ability to fight cancer, shifting the focus from targeting tumor cells to boosting the patient’s immune cells. These immunotherapies, including immune checkpoint inhibitors, work by increasing the anti-tumoral activity of immune cells, like T cells, within the tumor microenvironment. By activating the body’s defense mechanisms, these approaches can target the tumors and also address their heterogeneity with a more adaptive and sustained response to treatment. In these cases, multiplex imaging can be a game-changer for determining the most effective treatment approach.
Developing our surveillance cameras
To capture highly detailed images of a tumor, several key components are required, starting with antibodies. By tagging antibodies with fluorescent markers, we can simultaneously identify and distinguish different cell types, creating a detailed and vibrant mosaic of information (see header figure). This method differs from traditional pathology techniques such as hematoxylin and eosin staining, which lacks specificity for individual proteins, or chromogenic immunohistochemistry, which is typically limited to visualizing one or a few proteins per sample. Fluorescence imaging, on the other hand, allows the detection of multiple markers in the same sample, giving us a clear view of the tumor microenvironment.
After staining human tumor tissue with these antibodies, a scanner is used to capture the images for further analysis. In collaboration with a pathologist, cells—such as cytotoxic T cells and B cells—can be annotated. These labeled examples help train the AI algorithm, which then uses this information to automatically identify and classify the remaining cells in the images. This allows researchers to quickly recognize specific cell markers, categorize different cell types, and count their numbers and density. With this data in hand, we piece together new biomarkers (cancer related proteins), tissue patterns, and a patient’s clinical profile to gain a clear picture of each person’s unique case.
Listening in on cellular discussions
Multiplex imaging helps us study many cell types at the same time. Researchers are going beyond just counting cells with this method and are interested in cell interactions too – one research team from the US even found that three immune cell populations need to be close to each other in order for immunotherapy to effectively eliminate the tumors.
Being able to capture information in one image has opened up the exciting world of spatial biology. This is a new frontier in precision medicine where we can identify the distribution of cellular populations within heterogeneous tissues and determine how they relate to each other, even in 3D! This way, we can improve our understanding of cellular interactions, which in turn helps us to learn more about diseases and to develop better treatments.
A lens into the tumor neighborhood at jules bordet institute
And that’s how the power of photography can help us fight cancer! In Brussels, the Jules Bordet Institute is leading the way in this exciting field, with experts like Prof. Karen Willard-Gallo at the forefront of research into imaging tumors. Her lab focuses on the ‘meeting spots’ where immune cells come together to tackle threats called tertiary lymphoid structures. Thanks to multiplex imaging, we can now easily visualize these meeting hubs.
According to Prof. Willard-Gallo: “It is truly impressive when multiplex imaging of tissues is used to reveal immune cell interactions. In patients who respond well to treatment, we can visualize immune cells attacking and killing tumor cells. This technique is invaluable for analyzing how well treatments activate immune responses in clinical trials, leading to better long-term outcomes for cancer patients.”
A framed picture of the future of precision medicine
We are on the brink of a new era in precision oncology, and it is inspiring to see the progress being made. Though there’s a long road from lab to clinic, scientists are determined to go the distance and tools like multiplex imaging bring us closer to personalized therapies, targeting cancer more precisely than ever.
