Precise combination therapy of radiotherapy and immunotherapy guided by joint PD-L1 imaging and T-cell imaging.

backgroundPD-1/PD-L1 blockade therapy is often used in combination with radiotherapy (RT) to enhance therapeutic efficacy in clinic. However, the effectiveness of the combination therapy is still unsatisfactory due to the blindness in the administration schedule. More seriously, multiple dosing-induced deaths of PD-1/PD-L1 blockade often occur. Considering the urgency to enhance the efficacy and safety of the combination therapy, we pioneered a strategy that used SPECT/CT imaging of tumor PD-L1 expression and tumor-infiltrating T cells to guide and predict the combination therapy toward precision cancer therapy.

methodsSingle-photon emission computed tomography (SPECT)/CT imaging of a PD-L1-targeting probe (

resultsAs indicated by the dynamic imaging of tumor PD-L1 expression, the combination therapy achieved optimal antitumor efficacy, only when αPD-1 antibody was administrated during the window period of PD-L1 upregulation following RT. However, although PD-L1 imaging could indicate when the combination therapy was more effective, it could not accurately predict the prognosis of the combination therapy. The T-cell imaging showed that the changed number of tumor-infiltrating T cells, rather than the absolute number at a certain time, could predict the prognosis in the early stage. The single-cell RNA sequencing analysis showed that the αPD-1 therapy after RT during the time window could prevent or reverse the exhausted CD8

conclusionsPD-L1 imaging was suitable for guiding the timing of αPD-1 administration, while T-cell imaging was more suitable for predicting prognosis. The two imaging modalities jointly provide essential guidance to enhance the efficacy and safety of the combination therapy, facilitating individualized precision therapy. This imaging strategy can also be extrapolated to clinical practice for immunotherapy combined with other therapies to boost efficacy.