Recently, lncRNA DILC has been reported as a regulatory element in carcinogenesis of various tumors. Nevertheless, its impact on cancer immunity remains limited in breast cancer. The rationale of this study was to identify and correlate the impact of DILC and the PD-L1 inhibitor; Atezolizumab on the metastatic and oxidative function of PBMCs in tumor microenvironment (TME) of TNBC patients.
32 locally advanced TNBC peripheral blood samples were withdrawn. PBMCs isolation was performed using ficoll separation. A group of PBMCs was transfected with DILC siRNAs (using Hiperfect transfection reagent) and other group was treated with 100 nm Atezolizumab. Supernatants were collected after 48 hours and the metastatic and oxiditive profiles were analyzed by ELISA (TNF-α, MMP-9, nitric oxide, ROS and superoxide dismutase levels). One-way ANOVA statistical analysis was performed for multiple group comparison and Student's unpaired T-test for two group comparison.
MMP-9 was significantly downregulated, while TNF- α was remarkably upregulated, upon siDILC and ATE treatment in comparison to naïve PBMCs (P <0.0001 and P<0.0001, respectively). Additionally, NO was increased with ATE treatment (P <0.0001), however, it remained unaffected in siDILC compared to naïve PBMCs. Moreover, ROS levels were increased in siDILC nevertheless, it was decreased in ATE treated PBMCs (P <0.0001 and P<0.0001, respectively) compared to naïve PBMCs. Surprisingly, SOD levels remained unaffected with no significant change in siDILC and ATE treated PBMCs compared to naïve cells.
This study introduces DILC as an oncogenic lncRNA that is able to modulate immune response in TME of TNBC compared to the PD-L1 inhbitors. These data suggest DILC as a promising target that may contribute to resistance to immunotherapy in locally advanced TNBC.
German University in Cairo, Egypt.
Has not received any funding.
All authors have declared no conflicts of interest.