I study how breast cancer suppresses the immune system — specifically, how tumors drive T-cells from activation into exhaustion. Using patient-derived organoids and PBMC co-culture models, I'm building the experimental evidence for why immunotherapy fails, and what it might take to make it work.
Breast cancer kills because it spreads — and it spreads in part because tumors are remarkably good at disabling the immune cells sent to destroy them. My work focuses on T-cell activation and exhaustion in patient-derived co-culture models: using real tumor organoids and real immune cells to understand exactly how that suppression happens, and what it would take to reverse it.
The Chan Lab grows 3D tumor models directly from patient tissue — preserving the genetic and structural complexity of real breast cancers. These organoids serve as the platform for immunological co-culture experiments, providing a far more human-representative system than standard cell lines.
The lab's foundational discovery: breast cancer cells actively reprogram natural killer cells — stripping away their killing ability and redirecting them to assist metastasis. Reversing this corruption through targeted gene therapy is the lab's primary therapeutic objective.
Using CRISPR-Cas9 to recreate specific disease states in organoids, and testing whether Dr. Chan's gene therapy can restore immune cell function. This work provides the preclinical human tissue evidence needed to advance toward clinical trials.
Co-culturing patient-derived PBMCs with patient-derived breast cancer organoids to study what the tumor microenvironment does to T-cells. The central question: do T-cells activate and attack, or does the tumor suppress them into exhaustion? Using real patient tissue on both sides makes this a clinically meaningful model.
The next step: replacing circulating PBMCs with TILs isolated directly from resected tumor tissue. These T-cells have already been living inside the tumor — already shaped, and likely partially exhausted, by it. Comparing TIL behavior to that of naive PBMCs in the same organoid system will reveal how far the tumor has already driven immune suppression.
"Cancer cells educate natural killer cells to a metastasis-promoting cell state."— Chan et al., Journal of Cell Biology, 2020
Your body's NK cells are designed to hunt and destroy cancer. The Chan Lab discovered that breast cancer cells don't just hide from NK cells — they reprogram them through specific molecular switches (KLRG1 and TIGIT), stripping away their killing ability and redirecting them to help the tumor spread.
The critical finding: this corruption is reversible. Blocking those molecular switches in lab models restored NK cell function. The gene therapy Dr. Chan developed targets exactly this mechanism — and the organoid work I do provides the human tissue evidence that it works.
Standard immunotherapy drugs like PD-1 blockers do not address this problem. A successful therapy here would treat something no current approved drug touches.
The following is a 60-second AI-generated avatar presentation based on Caroline's research at the Chan Lab. Created using HeyGen.
Dr. Isaac Chan's lab is part of the Simmons Comprehensive Cancer Center — one of the leading cancer research institutions in the United States. The lab accepts donations directly, with 100% supporting research to end metastatic disease.