Monitoring the immune system supports several areas of immunology research, such as immuno-oncology, allergy and autoimmunity, and also includes research about monitoring responses to pathogenic infections, such as HIV, COVID-19 and others. With the increased awareness of antitumor immunity in mediating responses to immunotherapy approaches, the need for research on how to efficiently monitor immune responses has been steadily increasing.
Applications of immune monitoring
Monitoring tolerance in transplantation research
Immune monitoring is heavily used in clinical research seeking to understand the immune mechanisms driving tolerance in transplantation therapies under investigation. For example, research shows that in liver transplantation trials, passive tolerance such as spontaneous operational tolerance (SOT) can be monitored in the peripheral blood using markers of regulatory T cells, gamma delta T cells or NK cells. In kidney transplantation research trials, it can be monitored using transitional and IL10+ granzyme B+ regulatory B cells.1
Immuno-oncology
During immunotherapy research protocols, immune monitoring allows the research of the reactivity of immune responses at the populational and single-cell level. Major immunotherapy strategies, including CAR T cell therapy, transplantation and immune checkpoint inhibitors, can all benefit from immune monitoringresearch and also understand the molecular signatures to develop stratification strategies.2,3
Immune monitoring for precision medicine trials
Immune monitoring tools are also used in the clinical research that is required prior to clinical trials of biologic/biosimilars in order to research long-term safety and patient-specific therapeutic strategies to support precision medicine initiatives.4
Immune monitoring in allergy research
Allergic reactions involve different populations of immune cells, including antigen presenting cells (e.g., dendritic cells), mast cells, Ig-E producing B cells and T cells. Different types of allergic hypersensitivity exist based on the types of immune cells involved (e.g., IgG, IgM or antigen-specific T cells) and cytokines released (e.g., IL-4, IL5). Allergic reactions can also be non-IgG mediated. Measuring serum cytokines, complement activation or mitochondrial function are some strategies for measuring allergic responses in immune monitoring research.5,6
Immune monitoring in autoimmunity research
When the immune system fails to distinguish self from non-self and elicits responses that are typically meant for defending the host from antigens, autoimmune disorders ensue. With an increased understanding of the role of B cells in autoimmune disease pathogenesis, targeting B cells has also emerged as an alternative method for tackling autoimmune diseases. Memory and effector B cells could be targeted to prevent generation of pathogenic antibodies and subsequently block the synthesis of cytokines. B cells have been used increasingly in autoimmunity research.7
Immune monitoring for surveillance in immuno-oncology
The tumor microenvironment (TME) plays a critical role in the maintenance of the tumor and its response to therapy. The TME is composed of the tumor itself, its surroundings and all interacting cells and cellular processes the tumor can re-route to survive. These include cancer stem cells, infiltrating immune cells, blood vessels that carry nutrients, signaling molecules as well as the extracellular matrix (ECM) that allows migration of cancer cells to other sites.8
Immune monitoring in metabolism studies
Immune monitoring helps in understanding tumor metabolism and the metabolic share of the immunosuppressive TME. Nutrient access allows the tumor to gain essential replenishment to thrive and modulate key metabolic pathways (e.g., cholesterol synthesis, mitochondrial energy production, glucose metabolism) to help direct TME immune cell functions. Competition between tumor cells and T cells for the same nutrients leads to metabolic reprogramming of immune cell functions in the TME. Metabolic therapies (e.g., COX inhibitors for lipid metabolism, mTOR inhibitors for glucose metabolism) modify the nutrients made available to the TME and have been shown to reprogram tumor infiltrating T cells and re-boost antitumor immunity. Immune monitoring of tumor infiltrating immune cells gives access to the phenotype and functionality of these cells and informs on the immune activities in the TME, all affecting tumor burden.9