Rhythmic mild photothermal therapy enhancing anti-PD-L1 response for oral squamous cell carcinoma immunotherapy

The therapeutic efficacy of immune-blockade therapies is limited by low T-cell infiltration and PD-L1 expression in tumor tissue. Activating the body to generate tumor-specific immune responses, either actively or passively, can efficiently inhibit and kill tumors, which has promising research prospects. Here, we propose a therapeutic model that combines rhythmic mild photothermal therapy with immunotherapy to enhance the photothermal killing effect and reverse the immunosuppressive microenvironment, resulting in beneficial tumor therapeutic effects. We synthesized Y8 nanoparticles that are highly effective for photothermal therapy due to their excellent biosafety, photothermal properties, and controllability. Creatively, by converting continuous laser irradiation into an orchestrated rhythmic treatment, we have designed the photothermal treatment mode to mitigate the side effects of conventional photothermal treatment while enhancing the photothermal killing effect. At the same time, mild photothermal therapy can upregulate the expression of PD-L1 in tumors, and transform previously immune-insensitive “cold tumors” into immune-sensitive “hot tumors”, thereby significantly improving the efficacy of immunotherapy for oral cancer. This study confirms that the combination of rhythmic mPTT and immunotherapy can effectively achieve tumor ablation and synergistically enhance the efficacy of immunotherapy, providing a new strategy for the treatment of oral squamous cell carcinoma.