New Organ-on-a-Chip Platform Models Aging Immune Responses

A research team led by Dr. Vadim Jucaud at the Terasaki Institute has developed an organ-on-a-chip platform that recreates age-dependent immune responses to better evaluate cancer vaccines for older adults, who bear the highest cancer burden yet are frequently underrepresented in preclinical testing. The system focuses on addressing immunosenescence, the natural decline in immune function with age, which can substantially diminish cancer vaccine effectiveness but is rarely incorporated into vaccine development workflows.

Conventional 2D culture models fall short in capturing the complexity of age-specific immune behavior, limiting their ability to predict how vaccines will perform clinically in older patients. To overcome these limitations, Dr. Jucaud’s team designed a lymph node paracortex-inspired organ-on-a-chip that mimics key stages of the cancer vaccine response, including antigen presentation, activation of antigen-specific T cells, and subsequent tumor-directed cytotoxic activity. By integrating lymphocytes from both young and older donors, the platform reveals functional immune differences that naturally arise with age.

Using this system, the researchers observed that young antigen-presenting cells showed markedly stronger peptide presentation than older cells. This heightened presentation in younger cells resulted in greater activation of antigen-specific T cells and more robust cytotoxic effects against cancer cells. Importantly, these age-dependent disparities became evident only within the lymph node on-a-chip environment, emphasizing its ability to uncover biologically meaningful immune variations that standard 2D cultures fail to detect.

 “Unlike traditional 2D models, this advanced system replicates age-related immune responses, which is critical because older adults face the highest cancer risk and often have diminished immunity,” Dr. Jucaud explained. “By accurately modeling these conditions in vitro, our platform enables more reliable insights into cancer vaccine performance, therefore accelerating development and improving outcomes.”

By more faithfully reflecting the biology of aging, the lymph node on-a-chip platform provides a powerful tool to study how immunosenescence shapes cancer vaccine responses. This new tool, described recently in Lab on a Chip, may help inform the design of future immunotherapies tailored to older patients, supporting the development of cancer treatments that more effectively address the needs of those most affected by both aging and disease.