We generally consider cancer a disease of aging, as the rates of almost all types of cancer increase with age. Immunosenescenceis a biological process marked by a decline in immune system function due to the aging of cells. As humans age and undergo immunosenescence, the immune response weakens, increasing the risk of cancer and other illnesses.
These concepts considered together lead to a dramatic clinical concern: we see a steep reduction in the efficacy of cancer vaccines in elderly patients, the same cohort accounting for the greatest number of cancer patients. This understanding would presumably dictate that age-related immune function be taken into account in oncology research. However, scientists perform the vast majority of cancer research and anti-cancer drug development in animal models that more closely mimic young ages.
To address the need for better model systems that account for immunosenescence in cancer vaccine testing, researchers developed a new platform called the lymph node paracortex on-a-chip (LNPoC). A recent study in Lab on a Chip details how this technology can reproduce age-dependent immune responses to cancer vaccines. LNPoC can mirror antigen presentation, antigen-specific T cell activation, and antitumoral responses in vitro.
The data demonstrates that antigen-presenting cells (APCs), the immune cells responsible for finding antigens, foreign substances in the body that elicit an immune response, and educating the rest of the immune system about their presence in order to mount an immune response. APCs play an important role in vaccination, as they recognize the antigens included in the vaccine, and “present” them to other immune cells. This results in a process that trains the immune system to respond quickly when it encounters similar substances in the future.
The researchers obtained APCs from young (~6 weeks) and aged (~35 weeks) mice and found that the younger mice showed enhanced presentation of the vaccine antigen. This led to improved activation and killing ability in T cells, the immune cells responsible for killing cancer cells, in young mice. Further, young mice experienced better tumor control than their aged counterparts.
The researchers observed an age-dependent dichotomy in cells from young and aged mice in the LNPoC system, but not in traditional cell culture. These findings demonstrate LNPoC’s unique ability to interrogate the impact of immunosenescence on cancer vaccines, presenting a valuable model system to inform cancer research, particularly while accounting for age-related immune factors.
Sources: Nat Age, Signal Trans Target Ther, Lab Chip
