A three musketeers tactic for inclining interferon-γ as a comradein-arm to reinforce the synergistic-tumoricidal therapy

Interferon-gamma (IFN-gamma), secreted by activated T cells predominantly, plays a crucial performance in the tumoricidal immune response. Unfortunately, a high level of IFN-gamma severely ignites the immunosuppressive response, especially by increasing the expression of immune checkpoint programmed death-ligand 1 (PD-L1) and immunoregulatory enzyme indoleamine 2,3-dioxygenase 1 (IDO-1). Herein, we have explored a versatile IFN-gamma-nano-integrator (aPD-L1-SH@Ce6@NLG919-PEG, simplified as CNDP) to establish a positive anti-tumor feedback loop to amplify the IFN-gamma-mediated tumoricidal effect. In this nanointegrator, photosensitizer chlorin e6 (Ce6) mediates photodynamic therapy (PDT) to re-shape immunogenicity and activate the adaptive immune response, followed by the secretion of high-level IFN-gamma to struggle tumor cells. IDO-1 inhibitor (NLG919) afterwards mitigates the immunosuppressive behavior of IFN-gamma by neutralizing the function of IDO-1. To turn waste into wealth, anti-PD-L1 (aPD-L1) antibodies are technically integrated into the nano-integrator to propel the precise attack of breast cancer through ascending PD-L1 blockade. Together, this three musketeers nano-integrator tumoricidal tactic may give a unique insight into the clinical anti-tumor therapy.

Automated summary

IFN-gamma plays a crucial role in anti-tumor immunity, but high levels can lead to immunosuppression; the nano-integrator CNDP establishes a positive feedback loop to amplify IFN-gamma's tumoricidal effect; by combining PDT, IDO-1 inhibition, and PD-L1 blockade, this nano-integrator offers a new strategy for anti-tumor therapy.