The Chan Lab at UT Southwestern is developing a gene therapy to reverse that betrayal — and stop metastatic breast cancer before it starts.
Caroline is my granddaughter — and she is doing work that I believe deserves far more visibility than it gets. She's a Research Assistant at the Chan Lab at UT Southwestern Medical Center, and what she's working on sits at the precise intersection of everything I find most compelling: biology, technology, systems thinking, and the fundamental question of how life works. When I learned the details of her research, I realized it was one of the most important things I'd encountered in years. I wanted to share it here, in plain language, for anyone willing to pay attention.
This page is my attempt to explain genuinely extraordinary science to a general audience. None of this is hype. The Chan Lab's discoveries are published, peer-reviewed, and internationally recognized. What follows is the real story.
Your body is equipped with a type of immune cell called a Natural Killer (NK) cell. Their job, as the name suggests, is to hunt down and destroy dangerous cells — including cancer. They're particularly effective against the invasive cancer cells that try to break away from a tumor and spread through the body.
For decades, researchers assumed that cancer simply hid from NK cells — slipping past immune surveillance through camouflage. Dr. Chan's lab discovered something far more disturbing, and far more interesting.
Cancer doesn't just hide from NK cells. It actively reprograms them — stripping away their killing ability and redirecting them to assist the tumor's spread. Your own immune system's soldiers are turned into collaborators.
— Chan et al., Journal of Cell Biology, 2020
The mechanism involves specific molecular switches. When NK cells are exposed to tumor cells, two inhibitory receptors — KLRG1 and TIGIT — become overexpressed, effectively locking the NK cells into a dormant, tumor-promoting state. The cancer has essentially changed the lock on the door.
The critical finding that followed: this corruption is reversible. Blocking KLRG1 or TIGIT, or using epigenetic drugs that inhibit DNA methyltransferases (DNMT inhibitors), restored NK cell killing ability in lab models. The door can be unlocked again.
While the lab's core discovery centers on NK cells, understanding how tumors suppress the broader immune system is equally critical. Caroline's work focuses on the adaptive immune arm — specifically T-cells — and how breast cancer drives them from activation into exhaustion.
Caroline co-cultures patient-derived peripheral blood mononuclear cells (PBMCs) with patient-derived breast cancer organoids — watching in real time whether T-cells activate and attack the tumor, or get suppressed into exhaustion by it. With real patient tissue on both sides of the experiment, this is one of the most human-representative models of tumor immune evasion currently being run in the lab.
T-cell exhaustion is one of the central reasons immunotherapy fails in breast cancer. When T-cells are continuously exposed to tumor signals, they progressively lose their ability to fight — upregulating inhibitory receptors and shutting down their killing machinery. By modeling this process in patient-derived tissue, Caroline's experiments can reveal exactly what the tumor microenvironment does to T-cells over time.
The Chan Lab hasn't stopped at basic discovery. They've already translated this NK cell biology into a practical clinical tool — demonstrating the lab's commitment to research that reaches patients, not just journals.
By analyzing 236,363 cells from 119 breast tumor samples across eight datasets — the largest single-cell RNA sequencing analysis of breast cancer to date — the lab identified 10 distinct categories of breast cancer cells (vs. the 3 categories clinicians typically use). By mapping how these cancer cell subtypes interact with NK cells and other immune cells, they built a tool called InteractPrint that can accurately predict which patients will respond to immunotherapy — before they even begin treatment.
This is precision medicine in practice: instead of treating all HR+ breast cancer patients the same way, InteractPrint points toward which patients are likely to benefit from which therapies — potentially sparing others from treatments that won't work while directing effective ones to those who need them most.
Immunotherapy has been one of cancer medicine's great success stories over the past decade. But most immunotherapy targets T cells — a different arm of the immune system. Standard checkpoint inhibitors like PD-1 blockers have limited efficacy in breast cancer, and critically, they do not address the NK cell corruption problem the Chan Lab has identified. A therapy that restores NK cell function would be treating something that current drugs completely miss.
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