Cancer immunotherapies aim to overcome the immune-suppressive barriers in the tumor microenvironment through activation or modulation of the innate or adaptive immune signals. Non-invasive imaging approaches such as positron emission tomography (PET) and magnetic resonance imaging (MRI) enable visualizing the tumor microenvironment's immune compositions and dynamic changes in response to immunotherapy. Integrated PET/MRI enables simultaneous in vivo tracking of more than one immune target in the tumor, informing the development of more efficient immunotherapies.
B7-H4 is a recently discovered immune checkpoint protein that inhibits anti-tumoral T-cell function. We present a new imaging approach using a newly developed PET probe for imaging B7-H4 in mouse models of prostate cancer and osteosarcomas. Since B7-H4 inhibits the interaction between T-cells and tumor-associated macrophages (TAMs), we combined our imaging approach with ferumoxytol-enhanced MRI to track tumor-associated macrophages (TAMs) simultaneously. We demonstrate how B7-H4 expression on prostate cancers and osteosarcomas can be quantified with PET imaging. In addition, we show how integrated PET/MRI can demonstrate TAM activation after the B7-H4 blockade. We then investigate the ability of our integrated PET/MRI approach to predict tumor response to different combination immunotherapies by quantifying B7-H4 expression and TAM responses in the tumor microenvironment.
