With regard to immunogenicity and biomarkers that predict response to immunotherapy, accurate insight into all tumor lesions in individual patients is urgently needed. The tumor immune response is a highly dynamic interplay between tumor cells, immune cells and other molecules with marked heterogeneity between and even within tumor lesions. This review shows that molecular imaging strategies can enable visualization of various components that are important in immunotherapy, especially tumor cells, immune cells, and ECM components.
This could potentially guide treatment decisions, which are becoming increasingly complex as shown by the numerous combination trials that are currently ongoing in immunotherapy.
2
The various molecular imaging strategies could contribute to patient selection upfront or early during immunotherapy. These strategies might answer questions about what immune cells and specific immune cell populations are present before and during immunotherapy.
Moreover, these imaging strategies could provide insight into the mechanisms underlying cancer immunotherapy. For example, immune cell targeting tracers, with short-lived tracers such as [18F]FB-IL2, could be used shortly before imaging with radiolabeled immune checkpoint targeting molecules, with isotopes with a long half-life such as 89Zr. This would provide non-invasive, whole body information, not only about the presence of immune cells, but also about the biodistribution of immune checkpoint targeting drugs. Together with analysis of tumor biopsy, providing information on DNA, RNA and protein, a complete data set can be assembled. Moreover, combinations with other imaging modalities, such as optical imaging using fluorescent-labeled immune checkpoint targeting molecules, would provide even more information on tumor characteristics.
Funding: this work was supported by ERC Advanced Grant: OnQview, and Dutch Cancer Society Grant: RUG 2016-10034.
Appendix A. Supplementary materials
1. Search strategy, selection method and full search 2. Supplementary Figure 1
3. Supplementary Table 1 4. Supplementary Table 2 5. Supplementary Table 3 6. Supplementary Table 4 7. Supplementary References
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