Macrophages hold the key to cancer’s inner sanctum

All malignancies contain tumor-associated macrophages (TAMs) that facilitate cancer growth by secreting chemicals to elicit angiogenesis and shield the cancer from the immune system. The abundance of TAMs is a reflection of invasiveness and metastatic potential. TAMs will actively ingest ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles following intravenous administration and will store them as large lysosomal aggregates which can be imaged with MRI and ultrasound and visualized or quantitated in tissue biopsies. Since the USPIO also enhances regional lymph nodes, it is possible to include this information for more accurate cancer staging. The USPIO aggregates surprisingly also serve as heat sinks and can enhance hyperthermic regimens with focal laser, focused microwaves, or high-intensity focused ultrasound (HIFU). The hyperthermic intervention can be chosen based upon accessibility for the selected energy source. By sustaining an intratumoral elevation of temperature for an effective period of time, ablation of a small or large fraction of the TAMs and cancer cells can be achieved. Thus, for aggressive cancer, USPIO is a theragnostic agent. Following USPIO-enhanced hyperthermia, the resulting debris will slowly reach the regional lymphatics and immune recognition may result. An effective vaccine or adjuvant could be injected peritumorally to improve immunorecognition of that patient’s cancer. The field of immunotherapy is being intensely explored at present. Using the theragnostic properties of USPIOs that are accumulated in the TAMs may prove useful in further attempts to make immunotherapy successful. This intervention could be utilized at any stage of cancer therapy. Should immunological recognition occur, an abscopal response may be achieved for that patient and for his/her cancer. This would truly be personalized cancer therapy.