Grew Cancer and Immune Cells Together... Found Why Cancer Drug Effectiveness Varies [Reading Science]

Seoul National University Team Develops Personalized 3D Kidney Cancer Model
Recreates Patient-Specific Responses to Immunotherapy... Published in Nature

Even when patients have the same type of cancer and receive the same immunotherapy drug, treatment outcomes vary from person to person. This is because treatment outcomes are influenced not only by the genetic characteristics of cancer cells but also by their interactions with surrounding cells. A Korean research team has developed a technology that recreates tumors from actual cancer patients in the laboratory, making it possible to analyze the causes of these differences.

Seoul National University announced on October 28 that a research team led by Professor Shin Geunyu of its Department of Biological Sciences had developed a three-dimensional cancer model called a "cancer assembloid," combining cancer cells, surrounding tissue cells, and immune cells from patients with kidney cancer. The findings were published in the international journal Nature that day.

Reproducing patient-specific responses to immunotherapy in cancer assembloids. Photo provided by the research team.

The key innovation is that, rather than relying on the conventional approach of culturing only cancer cells, the team recreated multiple cell types that make up tumors in actual patients. This enabled the researchers to model the varying responses to immunotherapy among patients and identify interactions between cells that affect treatment outcomes.

Cancer Cells Alone Are Not Enough... Recreating the Tumor Microenvironment

Three-dimensional cancer cell cultures known as "cancer organoids" have already been used in drug development and research into responses to cancer treatments. Organoids are experimental models that recreate some of the structure and function of actual organs or tissues and are often called "mini-organs." However, it has been difficult to adequately reproduce the immune cells and stromal cells surrounding cancer cells.

In actual tumors, cancer cells do not exist alone. Nearby fibroblasts, immune cells, and other cells constantly exchange signals, affecting cancer growth and responses to treatment. This is why observing cancer cells alone cannot fully explain why patients respond differently to the same cancer treatment.

The research team created cancer assembloids by selectively combining cancer cells obtained from kidney cancer patients with cancer-associated fibroblasts (CAFs) and immune cells that had infiltrated the tumors. Cancer-associated fibroblasts are cells that influence tumor growth and immune responses in the area around cancer cells.

The cancer assembloids recreated key histological features of actual patient tumors. In particular, they also modeled the varying responses among patients to anti-PD-1 treatment, an immune checkpoint inhibitor that helps immune cells attack cancer cells.

Formation of cancer assembloids over time. Provided by the research team.

The Effectiveness of Immunotherapy Depends on "Communication" Between Cancer Cells and Surrounding Cells

The research team also developed a technology that can selectively regulate the genes in each cell type. This makes it possible to analyze how the effectiveness of immunotherapy changes when specific functions in cancer cells or surrounding cells are altered.

Experiments showed that in patients who responded well to immunotherapy, signaling between cancer cells and surrounding cancer-associated fibroblasts played an important role in maintaining the anticancer activity of immune cells. In contrast, these interactions did not function properly in patients whose treatment outcomes were poor.

The findings show that the effectiveness of immunotherapy is not determined solely by the characteristics of one cell type, such as cancer cells or immune cells, but can vary depending on the complex relationships among the different cells that make up a tumor.

The research team expects that cancer assembloids could help predict individual patients' responses to immunotherapy and identify new combination treatment strategies to improve the effectiveness of existing drugs.

Research team photo (from left: researcher Lee Juhee, Professor Shin Geunyu, Dr. Kim Eunji, and graduate student Kim Yunhee). Provided by Seoul National University.

However, this study analyzed treatment responses and their causes in experimental models made from patient-derived cells. Further validation of predictive accuracy and reproducibility is needed before the technology can be used in clinical practice to select the most suitable cancer treatment for individual patients.

Professor Shin said, "Until now, there has been a shortage of human tumor models capable of faithfully reproducing in three dimensions the complex composition and pathological and physiological characteristics of actual tumor tissue, including immune cells. We expect the cancer assembloid developed in this study to serve as a new platform for research into personalized treatments and drug development."

Kim Eunji, a research professor at Seoul National University's Institute of Genetic Engineering and the study's first author, explained, "We confirmed that responses to immunotherapy can vary not only according to the characteristics of one cell type, such as cancer cells or immune cells, but also as a result of interactions among tumor cells, stromal cells, and immune cells."

Researchers from Samsung Medical Center and Seoul National University Hospital also participated in the study.

This content was produced with the assistance of AI translation services.