Key points are not available for this paper at this time.
Immune checkpoint blockade (ICB) therapy is promising to revolutionize cancer regimens, but the low response rate and the lack of a suitable patient stratification method have impeded universal profit to cancer patients. Noninvasive positron emission tomography (PET) imaging in the whole body, upon coupling with specific biomarkers closely related to the immune response, could provide spatiotemporal information to prescribe cancer therapy. Herein, we demonstrate that antisilencing function 1a (ASF1a) could serve as a biomarker target to delineate tumor immune microenvironments by immune PET (iPET). The iPET radiotracer (68Ga-AP1) is designed to target ASF1a in tumors and predict immune response, and the signal intensity predicts anti-PD-1 (αPD-1) therapy response in a negative correlation manner. The ICB-resistant tumors with a high level of ASF1a as revealed by iPET (ASF1aHigh-iPET) are prescribed to be treated by either the combined 177Lu-labeled AP1 and αPD-1 or the standalone α particle-emitting 225Ac-labeled AP1, both achieving enhanced therapeutic efficacy and prolonged survival time. Our study not only replenishes the iPET arsenal for immune-related response evaluation by designing a reliable biomarker and a facile radiotracer but also provides optional therapeutic strategies for ICB-resistant tumors with versatile radionuclide-labeled AP1 peptides, which is promising for real-time clinical diagnosis and individualized therapy planning simultaneously.
Shi et al. (Wed,) studied this question.