Immunotherapy has revolutionised the treatment of cancer. However, while it shows high efficacy against certain tumours, immunotherapy is not effective against all types of cancers, or in all patients. For the development of more effective immunotherapies against a greater variety of cancers, a better understanding of the interaction between tumours and the immune system is needed. Biomarkers serve as useful indicators of the immune landscape, enabling scientists to gain deeper insight into the changes that occur during tumour progression. Profiling the immune landscape assists researchers to predict patient response to immunotherapy, monitor the tumour microenvironment, and the identification of biomarkers of adverse immune reactions. These insights can be used to guide the development of personalised therapies to improve patient outcomes.
The Complexities of the Tumour-immune Landscape
Alongside the transformation of cancer treatment, with both improved therapeutic efficacy and promise for future application, immunotherapy has also led to a deeper understanding of tumours and their surrounding landscape, including the tumour microenvironment (TME) and the immune system. The TME is a complex and evolving ecosystem, constituting changes to the extracellular matrix, environmental factors, and the presence of different cell types alongside the tumour cells. These changes help cancer cells to survive, which is partly achieved by influencing the interaction between tumours and the immune system. Understanding this complexity is important to provide insights into the mechanisms by which cancer cells adapt to survive. Cancer immunology focuses on the study of this interaction between tumours and the immune system and has revealed crucial insights leading to the development of cell therapies, immune checkpoint inhibitors (ICIs), monoclonal antibodies, and cancer vaccines.
One of the many strategies cancers use to survive and progress involves evading detection by the immune system, which is achieved through a variety of mechanisms. It is well known that the TME can suppress immune activity by modifying the expression of immune checkpoint receptors and their ligands. The first ICI approved by the FDA for treatment of cancer was ipilimumab, an antibody targeting cytotoxic T lymphocyte-associated protein 4 (CTLA-4). Since then, ICIs targeting programmed cell death 1 (PD-1), and its ligand PD-L1, have also been approved, demonstrating promising efficacy against metastatic melanoma, urothelial carcinoma, non-small cell lung cancer, and Merkel cell carcinoma. Whilst efficacious in some patients, others either do not respond to ICIs or experience tumour regression but develop resistance to ICIs over time.
