Fluorine assembly nanocluster breaks the shackles of immunosuppression to turn the cold tumor hot
Menée in vitro et à l'aide d'un modèle murin de cancer métastatique du sein, cette étude met en évidence l'intérêt d'un complexe moléculaire fluoré qui, sous l'action d'un laser, libère des espèces réactives de l'oxygène et et des molécules à base de cisplatine permettant de rendre immunogène une tumeur non détectée initialement par le système immunitaire
“Cold” tumors are good at camouflaging themselves, thus making it difficult for the immune system to recognize and to construct a great barrier for cancer immunotherapies. New methods that could awaken the immune system, enhance T cells and antigen-presenting cells (APCs) trafficking, and relieve immunosuppression to treat cold tumors are urgently in need. Here, we first report a chemically ingenious nanocluster FS@PMPt assembly by fluorine–fluorine interaction to regulate the immune process. The nanocluster not only increased the infiltration of immunopositive cells from the outside but also decreased the immunosuppressive cells from the inside to break the shackles of immunosuppression, which provides a promising paradigm for improving the anti–cold tumor immunotherapy.Clinical investigations have shown that a nonimmunogenic “cold” tumor is usually accompanied by few immunopositive cells and more immunosuppressive cells in the tumor microenvironment (TME), which is still the bottleneck of immune activation. Here, a fluorine assembly nanocluster was explored to break the shackles of immunosuppression, reawaken the immune system, and turn the cold tumor “hot.” Once under laser irradiation, FS@PMPt produces sufficient reactive oxygen species (ROS) to fracture the ROS-sensitive linker, thus releasing the cisplatin conjugated PMPt to penetrate into the tumors and kill the regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Meanwhile, ROS will induce potent immunogenic cell death (ICD) and further promote the accumulation of dendritic cells (DCs) and T cells, therefore not only increasing the infiltration of immunopositive cells from the outside but also reducing the immunosuppressive cells from the inside to break through the bottleneck of immune activation. The FS@PMPt nanocluster regulates the immune process in TME from negative to positive, from shallow to deep, to turn the cold tumor into a hot tumor and provoke a robust antitumor immune response.All study data are available in the article and SI Appendix.