ACSL4-programmed sphingomyelin metabolism rejuvenates tumor-infiltrating T-cells to enhance the efficacy of anti-PD-1 immunotherapy

To investigate whether the expression of ACSL4 may alter the anti-tumor effecet of T-cells, we conditionally knocked out the Acsl4 gene in mouse T-cells (Acsl4-cKO) as descried in Wang et al. Redox Biol 2022. To further demonstrate the importance of SM in ACSL4-mediated T-cell anti-tumor immunity, we conducted a complementary study by intra-tumoral injection of SM in subcutaneous MC38 tumors inoculated in Acsl4-cKO mice. Overall design: Tumor-infiltrating CD8+ T-cells from MC38 inoculted Acsl4-cKO mice treated with vehicle or SM, or control mice were isolated were isolated by FACS and analyzed using ATAC-seq.