Study on the immunotherapy effect of Immunogenic Cell Death (ICD) in exosomes secreted from breast cancer cells under the effect of photothermal therapy

Abstract

Abstract: Background: In cancer treatment, therapeutic methods that lead to immunogenic cell death (ICD) have great importance. Secreted factors from dying cancer cells, such as DAMPs, trigger the ICD against cancer, which can also be secreted by exosomes. In different stress and therapeutic conditions, the profile of secreted exosomal DAMPs changes which can play the role in stimulating or suppressing the immune system. Method: In this study, the changes of secreted exosomal DAMPs expression (HSP70, HSP90 and HSMGB-1) from breast cancer cells treated with photothermal therapy (PTT) were investigated and their potential in inducing an immune response in the tumor microenvironment (TME) in terms of the expression of inflammatory factors (IL-6, IL-12 and IL-1β), the infiltration of T cells (CD4 and 8 CD) into the tumor, and the expression of the PD-L1 factor were investigated. All factors were also studied for hyperthermia as a non-nano method. Results: Both PTT and hyperthermia methods increased the secretion of exosomes and exosomal DAMPs from cancer cells. The mechanism of cell death in PTT and hyperthermia was secondary apoptosis and primary apoptosis, respectively with differences in the expression of different DAMPs. In the animal study, injected exosomes successfully increased inflammatory factors (IL-6, IL-12, and IL-1β), and T-cell permeability in the TME, which resulted in inhibition of tumor growth. However, PTT-derived exosomes performed better than hyperthermia. In response to the changes in TME by injected exosomes, the expression of PD-L1 was increased in the tumor. Discussion: In this study, both methods were successful in inducing death to cancer cells and increasing exosomal DAMPs secretion, which had differences in the expression of diverse DAMPs. In the animal study, PTT performed better than hyperthermia in inhibiting cancer growth. These results can be derived from the differences in the mechanism of cell death and expression of DAMPs in both methods. The increase in T cell permeability and PD-L1 expression indicates the successful stimulation of the TME by injected exosomes.