Imaging the immune response to monitor tumor immunotherapy

The goal of cancer immunotherapy is to promote antitumor immunity, and novel approaches include vaccination, adoptive transfer of tumor-reactive T cells, and administration of monoclonal antibodies and small molecules that target immune regulatory pathways. The molecular and cellular events responsible for tumor rejection are not completely defined and correlative studies have been used to help understand the mechanisms and extent of immune activation and tumor regression with these approaches. The real-time monitoring of immune responses to immunotherapy has been challenging as specific cell subsets may be difficult to define, and molecular pathways have evolved functionally diverse outcomes in different cells and in different tissues. Recently, improvements in optics and digital imaging have led to novel imaging techniques that make it possible to track the migration of individual immune cells ex vivo and in vivo, and to detect the dynamic interactions between T cells and antigen-presenting cells or tumor cells within complex microenvironments, including lymphoid tissue and established tumors. This review will explain some of the more established imaging techniques and discuss their role in monitoring the immune response in patients treated with various tumor immunotherapy approaches.