RESUMEN
Aim: Exosomal damage-associated molecular patterns can play a key role in immunostimulation and changing the cold tumor microenvironment to hot. Materials & methods: This study examined the immunostimulation effect of photothermal and hyperthermia-treated 4T1 cell-derived exosomes on 4T1 cell-induced breast tumors in BALB/c animal models. Exosomes were characterized for HSP70, HSP90 and HMGB-1 before injection into mice and tumor tissues were analyzed for IL-6, IL-12 and IL-1ß, CD4 and CD8 T-cell permeability, and PD-L1 expression. Results: Thermal treatments increased high damage-associated molecular patterns containing exosome secretion and the permeability of T cells to tumors, leading to tumor growth inhibition. Conclusion: Photothermal-derived exosomes showed higher damage-associated molecular patterns than hyperthermia with a higher immunostimulation and inhibiting tumor growth effect.
This research explored the impact of using tiny dying cancer cell-derived particles known as exosomes to activate the immune system to fight against breast tumors in animal models. These exosomes contain specific molecules that can trigger the immune response and alter the environment surrounding the tumor. Researchers applied two different treatments, photothermal and hyperthermia, to kill the cancer cells and obtain these exosomes. Both treatments involved using heat to kill the cells. The study revealed that exosomes derived through the photothermal method exhibited higher levels of these immune-activating molecules compared with those obtained through hyperthermia. Upon injecting these exosomes into the animal models, they enhanced the ability of the immune cells to enter the tumors, resulting in a reduction in tumor growth. Overall, the findings indicate that using exosomes obtained through the photothermal method may be more effective in stimulating the immune system to fight against cancer and inhibiting tumor growth, as opposed to using exosomes obtained through hyperthermia.
Asunto(s)
Exosomas , Neoplasias , Animales , Ratones , Exosomas/metabolismo , Linfocitos T CD8-positivos , Neoplasias/metabolismo , Inmunoterapia , Línea Celular Tumoral , Microambiente TumoralRESUMEN
The tumor microenvironment (TME) within and around a tumor is a complex interacting mixture of tumor cells with various stromal cells, including endothelial cells, fibroblasts, and immune cells. In the early steps of tumor formation, the local microenvironment tends to oppose carcinogenesis, while with cancer progression, the microenvironment skews into a protumoral TME and the tumor influences stromal cells to provide tumor-supporting functions. The creation and development of cancer are dependent on escape from immune recognition predominantly by influencing stromal cells, particularly immune cells, to suppress antitumor immunity. This overall process is generally called immunoediting and has been categorized into three phases; elimination, equilibrium, and escape. Interaction of tumor cells with stromal cells in the TME is mediated generally by cell-to-cell contact, cytokines, growth factors, and extracellular vesicles (EVs). The least well studied are EVs (especially exosomes), which are nanoparticle-sized bilayer membrane vesicles released by many cell types that participate in cell/cell communication. EVs carry various proteins, nucleic acids, lipids, and small molecules that influence cells that ingest the EVs. Tumor-derived extracellular vesicles (TEVs) play a significant role in every stage of immunoediting, and their cargoes change from immune-activating in the early stages of immunoediting into immunosuppressing in the escape phase. In addition, their cargos change with different treatments or stress conditions and can be influenced to be more immune stimulatory against cancer. This review focuses on the emerging understanding of how TEVs affect the differentiation and effector functions of stromal cells and their role in immunoediting, from the early stages of immunoediting to immune escape. Consideration of how TEVs can be therapeutically utilized includes different treatments that can modify TEV to support cancer immunotherapy.