Research Focus Area
Systems Immunology: Cracking the Tumor Microenvironment
How it works
Every solid tumor is surrounded by a tumor microenvironment (TME): a mix of immune cells, structuring tissue, and signaling molecules that the cancer recruits and reshapes to defend itself. Some of these components attack the tumor. Others — often the majority — get hijacked into shielding it.
The TME is what makes solid tumors so much harder to treat than blood cancers. It can block T cells from physically reaching the tumor, exhaust the T cells that do get in, or dampen the immune response before it ever gets started. No single intervention has been able to take the TME apart, in part because no two tumors suppress the immune system the same way. What works in one cancer type or treatment stage may do nothing in another.
Systems immunology works in two steps. First, collect detailed data from real patients during treatment and use computational models to identify which specific TME mechanisms are actually driving resistance, in which cancers, and at which stage. Second, act on what those data reveal — using approaches like cell therapy, cytokines, synthetic biology, or in vivo engineering to modify or deplete the cells responsible.
Why it matters
Most attempts to target the TME have struggled — not from a lack of effort, but because the TME is more complex than any one therapy can address. Multiple suppressive mechanisms typically work together, and disabling just one usually isn’t enough to change the outcome.
That complexity is also the opportunity. A clearer, data-driven map of how the TME suppresses immunity wouldn’t just unlock new treatments on its own. It would also make every other approach work better. Checkpoint inhibitors, cell therapies, and cancer vaccines all run into the same wall, put up by the TME. Breaking through that wall would immediately increase the effectiveness of all these other treatments.
What we’re doing
- Studying the immune cells that make up the TME — including macrophages, NK cells, and other innate immune cells — to understand why they so often end up suppressing the very immune response they could support.
- Investigating cancer-associated fibroblasts, the structural cells that build a physical and chemical barrier around tumors, blocking T cells from getting in.
- Examining how tumor cells themselves contribute to suppression, including the molecules and signaling pathways they use to recruit and reshape the surrounding environment.
- Researching how to strengthen dendritic cells and other antigen-presenting cells, which are often the rate-limiting step in starting any immune response, whether natural or vaccine-induced.
- Collecting expression and transcriptomic data across the Parker network to build the foundation for computational, data-driven approaches to understanding the TME.
What’s next
- Expanding patient data collection — combining clinical trial results, lab modeling, and cellular imaging — to generate the datasets machine learning needs to find real answers.
- Using computational models to generate testable hypotheses about which TME mechanisms matter most, in which cancers, and at which stage of treatment.
- Applying these insights to cell therapies and vaccines, engineering or modifying suppressive TME cell populations directly in the tumor rather than only working around them.