In the ageing European population, cancer has become the most common cause of death. Consequently, there is a growing need for screening programs for early detection of cancer and methods for monitoring of treatment effectiveness to improve cure rates and increase quality-of-life. However, many screening and monitoring methods do not provide sufficient sensitivity and specificity and/or are highly invasive. Thus, novel diagnostic techniques are required. Sensitive intra-tissue total body scanning is continuously performed by the monocyte-macrophage system. These cells are actively recruited to tissue damage, including tumor sites where they phagocytose apoptotic tumor cells. Once they have fulfilled their local tissue-cleaning task, they migrate via lymph vessels to lymph nodes to present (tumor-) antigens to T-cells and potentially recirculate to the blood stream, where they can be monitored and evaluated for their phagolysosomal contents by flow cytometry.
This project aimed to unravel phagocytosis of cancer cells, their digestion into tissue-specific and/or cancer-related protein fragments, the migration/recirculation of tissue macrophages (TiMas) to blood, and the detection of intra-phagolysosomal protein fragments in blood TiMas by antibodies. Building on this information, flow cytometric scanning of blood TiMas (TiMaScan) is being developed into a novel tool for early diagnosis and treatment monitoring in oncology, focusing on colon, lung, breast, prostate cancer and melanoma. TiMaScan diagnostics should be minimally-invasive (~2ml of blood), rapid, accurate, broadly available and cost-effective, only requiring a flow cytometer and appropriate antibodies against tissue-specific and/or cancer-related protein fragments. TiMaScan diagnostics might also be applicable for early diagnosis and disease monitoring in other medical conditions, in which tissue damage and/or inflammation plays a role (Figure 1).
