Time Rules the Efficacy of Immune Checkpoint Inhibitors in Photodynamic Therapy

Abstract

Lack of adequate effector T cells infiltrated in tumor isone of the main problems in the failure of immune checkpoint blockade therapy (ICBT). Photodynamic therapy (PDT) induced acute inflammation can sensitize tumors and activate T cells, thus assisting immune checkpoint inhibitors (ICI) against tumor growth and metastasis. T cells maturation and activation lag 3 to 7 days behind PDT. However, such timing in the combination therapy of ICI and PDT is commonly ignored in designing numerous multi-functional integrated nanomedicines. Herein, the authors illustrate that intervention timing of ICI after PDT affects the anti-tumor efficacy. A tumor-targeting nanomedicine is prepared by encapsulating indocyanine green into CD44 specifically binding material, a hyaluronic acid conjugated lipid poly(ethylene glycol). The PDT nanomedicine is designed to induce a robust immune response in tumor. The optimal group (Combo-STAR), ICI gave 5 days after PDT, significantly suppresses local tumor growth and eliminates metastasis. What should be highlighted is the time point of administration because if ICI is given too early, T cells are immature, otherwise, T cells are exhausted if ICI is given too late. This work presents theoretical guidance for raising awareness of intervention timing when augmenting ICBT with immune response inducers in clinic.

Combinatorial therapeutic approaches of photodynamic therapy and immune checkpoint blockade for colon cancer treatment

“…7, and 8). As reported recently by Wu Qinghua et al, the timing of ICI intervention after PDT plays an important role in the antitumor effect [53]. This P407-hydrogel-based combined therapy is based on repeated PDT and sustained anti-CTLA4 antibodies within 7 days which can be realized with a single dose of Fig.…”

Anti-tumor immunity enhancement by photodynamic therapy with talaporfin sodium and anti-programmed death 1 antibody

“…TS has been widely used in clinical applications. There are already several reports about PDT-triggered ICD plus ICIs ( Table S1 ), 16 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 but the combination of TS-PDT and anti-PD-1 antibody was not examined. So, our study is the first report of the combination of TS-PDT and anti-PD-1 antibody, and that has significance and uniqueness.…”

Nanoparticles-based phototherapy systems for cancer treatment: Current status and clinical potential

“…The treatment schedule between laser irradiation, PDT and administration of immune checkpoint inhibitors should be optimized based on the molecular mechanisms of the immune activation promoted by PDT. Wu et al investigate the optimal schedule by inducing immunogenic cell death with HA-based NPs loaded with ICG and administered the immune checkpoint inhibitor at 0, 2, 5, or 8 days after the laser irradiation [ 267 ]. Only the treatment schedule with 5 days interval between the laser irradiation and the administration of the immune checkpoint inhibitor can control the 4T1 tumor growth and prevent the cancer metastasis ( Fig.…”

“…Furthermore, the authors also employed 3D stimulated Emission Deletion imaging with super resolution to visualize the interaction between T cells and cancer cells in the optimal treatment schedule. The three stages in the process of the enhanced immune blockade efficacy in optimal group were clearly observed [ 267 ].…”