Effect of ECP on intestinal immune cells in immune checkpoint inhibitor-induced colitis - batch2 [scRNA-Seq]
Immune Checkpoint Inhibitors (ICI) have proven to be beneficial against tumors by boosting anti-tumor immunity, however these therapies can induce severe inflammatory side effects in all tissues, named immune-related adverse events (irAE). The colon is affected most commonly. These cause termination of treatment. Until today, patients with irAEs received systemic immunosuppressive therapies. We have found ECP as a novel therapy, which causes immunomodulation in the inflamed tissue without systemic immunosuppression. To understand which immune cells are affected by ECP in the inflamed intestinal tract, mice were treated with DSS and anti-PD1 to induce colitis, comparable to patients suffering from ICI-induced irAEs. ECP showed beneficial effects in patients. Mice were transplanted with ECP-treated cells as treatment and scSeq was performed with Colon infiltrating CD45 positive cells. Naive mice, mice receiving DSS and isotype control and mice receiving DSS in combination with anti-PD1 and untreated splenocytes, served as control. Overall design: Mice were left untreated or treated with DSS and anti-PD1 to induce ICI-induced colitis. Mice treated with DSS and isotype served as control. As treatment, mice with ICI-induced colitis were transplanted with ECP-treated donor splenocytes. As control, mice with ICI-colitis were transplanted with untreated donor splenocytes. Colitis tissue was digested, dead cells were removed and CD45 positive cells were selected by magnetic cell sorting from the lamina propria. CD45 positive cells were processed for scRNA Seq.