Oxaliplatin and Checkpoint Inhibitor Induces Immunogenic Cells Death and Promotes Therapeutic Efficacy in the Model of Murine Triple Positive Breast Cancer.

Abstract

Various damage-associated molecular patterns (DAMPs) associated with immunogenic cell death (ICD) have been discovered, potentially leading to cancer cell elimination. Certain platinum-based compounds can trigger both cancer cell apoptosis and ICD. This study aims to investigate the effect of the therapy of anti- PDL1 with Oxaliplatin by increasing amount and increasing treatment duration of anti-PDL1 with Oxaliplatin in SK-Br-3, both in vitro and in vivo conditions. The study will use HER-2 (3+) breast cancer cell line, SKBr3. The cells will be treated with increasing concentrations of Oxaliplatin with anti-PDL1 for different durations. In vitro death of cancer cells will be measured by MTT assay, HMGB1 will be measured by western blot. Additionally, ATP release will be measured, mice will be injected with SK-Br-3 and treated with the combo therapy of anti-PDL1 with Oxaliplatin, and in vivo tumor growth will be recorded weekly for xenograft. The positive control for the experiments is cisplatin, and the negative control is IgG solution instead of aPDL1 and Oxaliplatin in PBS.There are three main possible results: (1) The combo therapy of Oxaliplatin with anti-PDL1 induces robust ICD in HER-2 triple positive breast cancer cells. (2) The combo therapy of Oxaliplatin with anti-PDL1 act as a stimulant for robust ICD in HER-2(3+) positive breast cancer cells. (3) The combo-therapy of Oxaliplatin with anti-PDL1 has no significant effect on inducing robust ICD in HER-2(3+) positive breast cancer cells. The result of the study will provide important insight into the preclinical effectiveness of Oxaliplatin with anti-PDL1 in treating HER-2 (3+) breast cancer, and it also sets the basis for future clinical studies of the drug. Future studies should focus on investigating the mechanism underlying Oxaliplatin with anti-PDL1 effectiveness in SK-Br-3.