The immune system has developed an intricate ability to sense a variety of biomolecules, allowing it to act as a vigilant sentinel in detecting and eliminating cancerous cells. For example, abnormal protein expression and modifications are detected through the presentation of short peptides by human leukocyte antigen (HLA) molecules, which are displayed on the surface of tumor cells and recognized by T lymphocytes. This recognition is not limited to unmodified peptides but extends to those with post-translational modifications such as glycosylation and phosphorylation, which can serve as important markers of cellular dysfunction in cancer.
Additionally, changes in lipid metabolism are sensed by the immune system through the selection of specific lipids presented by CD1 molecules. These lipids are then recognized by a distinct subset of T lymphocytes, adding another layer of immune surveillance. Cancer cell metabolism itself can also be detected through the binding of various metabolites to the MR1 molecule, which is recognized by another specialized set of T lymphocytes. This broad range of biomolecular sensing enables the immune system to effectively surveil cancer cells through multiple mechanisms, creating a comprehensive and multifaceted defense to target and eliminate tumors.
Recent advancements in multiomics approaches, including mass spectrometry, have become powerful tools in identifying novel cancer antigens. These tools provide detailed insights into the biomolecules that drive cancer, opening up new possibilities for developing targeted immunotherapies. In this presentation, I will explore the potential cross-talk between these different sensing mechanisms and provide new insights into the wide range of actionable biomolecules that could be leveraged in the development of innovative cancer immunotherapies. These discoveries offer promising avenues for enhancing anti-cancer immunity and advancing the field of cancer treatment.