Acyl-coA Binding Protein neutralization improves cancer immunosurveillance

The plasma concentrations of acyl coenzyme A binding protein (ACBP, also known as diazepam-binding inhibitor, DBI, or ‘endozepine’) increase with age and obesity, two parameters that are also the most important risk factors for cancer. In mice bearing MCA205 fibrosarcoma, antibody mediated ACBP/DBI neutralization enhanced the anticancer T-cell response in the context of chemoimmunotherapy. T-cells infiltrating MCA205 tumors were sorted and submitting to single-cell TCR sequencing and single-cell RNA sequencing (scRNAseq) to identify the mechanisms driving this improvement. C57Bl/6 mice were injected with 3E5 MCA205 cells subcutaneously. 8 days after injection they were treated intraperitoneally with one cycle of chemotherapy (10 mg/kg oxaliplatin) followed, 8 days later, by immunotherapy (200 µg anti-PD1). Simultaneously, half the mice were treated with anti-ACBP/DBI neutralizing antibody (n = 3), the other half with isotype control (n=3) (2.5 mg/kg every other day, from two days before chemotherapy to the day prior to immunotherapy). Tumors were collected two days after immunotherapy, dissociated and fluorescently labelled to sort CD4+ and CD8+ T cells. A CD4:CD8 ratio of 1:1 was analyzed by TCR/scRNAseq.