Exploring enhanced abscopal effect: Molecular imaging insights into tumor physiologic changes in combined radiation and PD-1 blockade therapy

Motivation: Radiation therapy (RT) for primary tumors triggers regression in non-irradiated metastatic lesions via the abscopal effect, can potentiate the effects of immune-checkpoint blockade on the non-treated tumors in the same animal. Goal(s): To examine physiological alterations of the treated tumor linked to the abscopal effect. Approach: We used MRI-based imaging techniques, such as EPR oximetry, DCE MRI, and 13C DNP MRI. Results: After RT and PD-1 blockade, we observed improved oxygenation, permeability, perfusion, and CD8+ T cell infiltration in metastatic (untreated) tumors. Interestingly, primary tumor with increased permeability and perfusion and reduced hypoxic fraction (HF10) before treatment correlated with augmented abscopal effect post-treatment. Impact: Metastatic tumor conditions improved with RT and ICB, enhancing oxygenation, permeability, perfusion, and CD8+ T cell infiltration. Primary tumor's elevated permeability and lower HF10 correlated with higher AE in metastatic tumors, confirmed through carbogen-enhanced perfusion.