A single-beam of light priming the immune responses and boosting cancer photoimmunotherapy

Mirroring the rapid clinical performance, immune checkpoint blockade (ICB) leads a remarkable clinical advance in combating cancer, but suffers poor response in most cancers. The low presence of tumor-infiltration lymphocytes and the poor immunogenicity in tumor microenvironment (TME) are the main factors hindering the effectiveness of ICB in the treatment of immunological "cold" tumors. Aiming at boosting immune response via TME modulation, we report a near-infrared laser-guided photoimmuno-strategy in which synergistic phototherapy, immune adjuvant, and ICB are integrated into one versatile nanoporphyrin platform. The prepared nanoporphyrins are self-assembled from purpurin18-lipids and have photodynamic/photothermal and immunomodulatory effects that can be tuned under a single laser irradiation, concomitant with fluorescence or MSOT imaging. In this work, the contributions of each component in the nanoporphyrin platform were specified. In particular, phototherapy-driven in situ tumor cell death provided abundant tumor-associated antigens to initiate immune responses. With the assist of spatiotemporally delivered immune adjuvant, phototherapy potentiated tumor immunogenicity, reprogrammed "cold" tumors into "hot" ones, and sensitized tumors to ICB therapy. Further combined with PD-L1 blockade, the photoimmune-strategy substantially stimulated tumor-specific immune-responses and long-term immunological memory against primary tumor, abscopal tumor as well as metastatic foci. Such single light-primed photoimmunotherapy offers a promising solution to overcome common hurdles in ICB treatment and can potentially be integrated into existing clinical practice.