Dual mitigation of immunosuppression combined with photothermal inhibition for highly effective primary tumor and metastases therapy

T-cell based immune response can attack cancer cells formidably when certain immune checkpoint (e.g., PD-1/PD-L1) is blocked. Unfortunately, PD-1/PD-L1 blockade only provoke limited immune response because the differentiation of tumor-reactive T lymphocytes is often suppressed by TGF-beta pathway. Namely, the combating cancer weapon is weakened. In this study, other than employing photothermal therapy (PTT) to eliminate the primary tumor, we also aimed to expose in situ tumor-associated antigens and exert immune response for metastases inhibition. This enhanced immunotherapeutic strategy is achieved by IR780/SB-505124 based nanoliposomes (Nano-IR-SB@Lip). Upon administration, TGF-beta pathway is inhibited by SB to drive effector T cells into a responsive state and reduce the infiltration of Treg cells, eventually greatly enhancing the weapon against cancer. In the meantime, the immunosuppressive protection of tumor cells is also neutralized by blocking PD1/PD-L1 immune checkpoint. By virtue of inherent characteristics of IR780, Nano-IR-SB@Lip can selectively accumulate, penetrate deeply in tumor tissues, and preferentially retain in mitochondria. The above features are of critical importance to tumor therapy. Thus, highly effective cancer immunotherapy is implemented via selective accumulation/deep penetration of Nano-IR-SB@Lip in tumor, achieving PTT induced immunogenic cell death and dual mitigation of immunosuppression strategy (TGF-beta inhibition/PD-1/PD-L1 blockade), which is a promising therapeutic modality for cancer.

Automated summary

This study introduces a novel immunotherapeutic strategy utilizing a specific nanoliposome combining photothermal therapy with immune induction methods to enhance immune response, reduce inhibitory factors, and effectively combat cancer.