Understanding the immune system is driving forward immunotherapy treatments that are available. However, finding new drug targets and developing improved drug therapeutic strategy requires a more in-depth understanding of the immune system and the tumour microenvironment (TME).
Entities such as cytokines, immune cells and molecular signals all contribute to the TME. Lauren Schewitz-Bowers, Senior Group Leader at Charles River explained that the tumour microenvironment is heterogenous and can vary from cancer to cancer and among different patient populations. Therefore, it is difficult to model the TME however Schewitz-Bowers and her group have conducted experiments aiming to recapitulate crucial immune-tumour dynamics.
Schewitz-Bowers developed an in vitro co-culture system using CD3 T cells, CD14 monocytes and tumour cells. The CD14 monocytes were differentiated into dendritic cells, which were then co-cultured with T cells and tumour cells. To measure the tumour cell killing activity and cytokine production, the team used apoptosis assays and flow cytometry.
Results from this experiment showed that T cells on their own displayed very little cytotoxic activity but the presences of mature dendritic cells significantly increased tumour killing. Furthermore, cytokine analysis revealed that dendritic cells promoted T cell activation, leading to the production of key factors like interferon-gamma and TNF-alpha. This was correlated with enhanced tumour elimination.
Schewitz also explored the role of antigen-specific T cells in tumour immunity. Antigen-specific T cells are crucial for long-term immune protection and are often expanded in response to therapeutic cancer vaccines. However, their low frequencies in vitro present challenges. Schewitz highlighted the complexity of replicating the TME in vitro and the need for continuous optimisation of these models.
