Organ-on-a-chip system reveals how aging weakens vaccine-driven anti-cancer immunity

Dr. Vadim Jucaud's lab at the Terasaki Institute has introduced a new organ-on-a-chip platform that recapitulates age-dependent immune responses, offering a more accurate testing bed for evaluating cancer vaccine performance in older adults, the population most affected by cancer and often overlooked in traditional preclinical testing.

Immunosenescence, the natural decline of the immune system with age, significantly reduces the effectiveness of cancer vaccines. Yet, despite its clinical importance, age-related immune decline is seldom incorporated into vaccine development pipelines. Current 2D culture systems are unable to capture these complex age-specific immune responses, thereby limiting their predictive value towards clinical translation.

To address this need, Dr. Vadim Jucaud's research team at the Terasaki Institute developed a lymph node paracortex-inspired organ-on-a-chip platform that models key steps in cancer vaccine immune responses, which are characterized by antigen presentation, antigen-specific T cell activation, and downstream tumor-specific cytotoxicity. By comparing immune responses from young and older lymphocytes, the lymph node on-a-chip platform captures functional differences that naturally emerge with age.

Using this platform, the team demonstrated that young antigen-presenting cells displayed significantly stronger peptide presentation compared to old cells. This increased activity led to higher activation of antigen-specific T cells and enhanced cytotoxicity against cancer cells. Notably, these age-dependent differences were detectable only with the lymph node on-a-chip system, underscoring its ability to reveal biologically relevant immune variations that traditional 2D cultures cannot.

This work introduces our lymph node on-a-chip platform for cancer vaccine testing. 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. By accurately modeling these conditions in vitro, our platform enables more reliable insights into cancer vaccine performance, therefore accelerating development and improving outcomes."

Dr. Vadim Jucaud, Principal Investigator and Assistant Professor, Terasaki Institute

By more accurately reflecting the biology of aging, this novel platform offers a valuable tool for understanding how immunosenescence influences cancer vaccine efficacy. This technology may help guide the development of next-generation immunotherapies designed to meet the needs of older patients, ensuring that emerging cancer treatments support those who depend on them most.