The T cell-myeloid axis in the success and failure of cancer immunotherapy

Abstract

As most patients still experience either primary or secondary resistance against immunotherapy, we aimed to identify what dictates immunotherapy response and searched for novel targets with the aim to ultimately improve therapy outcome. In Part I two immunosuppressive immune cells (Treg & CD163hi macrophages) and their mechanism of action were introduced and we showed that immunotherapy resistance could be relieved by specific targeting of these cells. In Part II we then revealed that unleashing the anti-tumor potential of inflammatory myeloid cells (iNOS+ neutrophils & macrophages) in the TME can contribute to total

tumor eradication. While the immunotherapeutic treatment strategies used in these studies (ICB, vaccination, bsAb) are all T-cell based, throughout this thesis we demonstrate that the response (or resistance) is dependent on several other cells in the TME, in which the myeloid-T cell interactions take the center stage.