“Artificial Lymph Node” May Help Train the Immune System To Kill Cancer Cells

A new study has found that implanting an “artificial lymph node” under the skin of mice may act as a hub to teach immune cells how to recognize and kill cancer cells, prolonging mouse survival and slowing tumor growth.

The research is published in Advanced Materials.

Kickstarting the anti-cancer immune response

Lymph nodes are tiny glands – mainly found in the neck, armpits and groin – that form key parts of the immune system.

“[Lymph nodes] are a landing spot where T cells, the immune system’s fighting cells, lay dormant, waiting to be activated to fight infections or other abnormal cells,” explained Dr. Natalie Livingston, the first author of the study and a postdoctoral researcher at Massachusetts General Hospital.

Hundreds of lymph nodes are spread throughout the body so that immune cells don’t have far to travel to mount an immune response. However, cancerous tumors can find ways to escape detection and killing by the immune system, making treatment difficult. But immunotherapies are helping to turn the tide.

“Because cancers can trick T cells into staying dormant, the artificial lymph node was designed to inform and activate T cells that are injected alongside the lymph node,” Livingston added.

Artificial lymph nodes show promise in mouse models

The research team developed the artificial lymph node using hyaluronic acid, a substance often used in biodegradable materials like wound healing patches.  It is also found naturally in the skin and joints and serves as a moisturizing substance in skincare products and cosmetics.

Hyaluronic acid also boasts the ability to connect with and boost the activation of T cells using a cell surface receptor, prompting the researchers to use hyaluronic acid as the scaffolding for their artificial lymph node. They also added other immune system-activating components such as major histocompatibility complex (MHC), human histocompatibility antigen (HLA) and molecules and antigens commonly found on cancer cells to “teach” immune cells what to aim for.

The finished product resulted in an artificial lymph node small enough to be placed under the skin, but large enough to avoid being carried away by the bloodstream – around 150 microns or double the width of a human hair.

The researchers next implanted the artificial lymph nodes in experimental mice bearing either melanoma or colon cancers to evaluate whether they could aid treatment.

They compared several groups of tumor-bearing mice injected with:

• Artificial lymph nodes and T cells
• Lymph nodes only
• T cells only
• Lymph nodes, T cells and an immunotherapy drug (an anti-PD-1 immune checkpoint inhibitor)

Mice who received the artificial lymph node, T cells and immunotherapy drug had the best survival rate with 3 of the 7 mice still alive after 33 days, while other groups lived only until approximately 26 days. They also had the slowest cancer growth rate, with tumors taking about 5 to 10 days longer to double in size compared to the other groups.

The artificial lymph node attracted an influx of other immune cells and served as an “immunologically active niche” to further stimulate the immune system. For example, administering T cells alongside the artificial lymph node led to T-cell numbers to grow by as much as nine times.

“In our approach, we inject T cells along with an artificial lymph node, and the T cells get primed and educated by the artificial lymph node inside of the body. Then, the T cells can travel anywhere to destroy cancer cells,” explained the study’s co-senior author  Jonathan Schneck, a professor of pathology at Johns Hopkins University School of Medicine.

“We blended the disciplines of materials science and immunology to create a potential therapy that forms its own immunology community – a kind of living drug,” said Schneck.

The researchers now plan to carry out additional laboratory studies to recruit more immune cells to the artificial lymph nodes by adding more signaling molecules.

Reference: Livingston NK, Hickey JW, Sim H, et al. In vivo stimulation of therapeutic antigen-specific T cells in an artificial lymph node matrix. Adv. Mater. 2024;36(23):2310043. doi: 10.1002/adma.202310043

This article is a rework of a press release issued by Johns Hopkins Medicine. Material has been edited for length and content.