Fig. 2

Cell-based therapies for the treatment of solid tumors: tumor recruitment, persistence, and local and systemic effects upon cell injection. A Injected T and NK cells are poorly recruited to the tumor sites due to lack of recruitment factors, abnormal blood vessels or extracellular matrix (ECM), and down-regulation of extravasation mediators. B T and NK cells that manage to infiltrate the tumor are rendered dysfunctional by many factors, such as interleukin (IL)−10 and transforming growth factor beta (TGF-β) secreted by immunosuppressive regulatory T (Treg) cells, M2 macrophages and myeloid-derived suppressor cells (MDSCs). C Activation of inhibitory immune checkpoint pathways, such as the programmed cell death protein 1 (PD-1) / programmed cell death protein 1-ligand (PD-L1) axes, also contributes to a dysfunctional phenotype of tumor infiltrating T and NK cells. D Injected T and NK cells upon activation and proliferation can trigger systemic inflammation which leads to the release of pro-inflammatory factors, such as cytokines, sometimes resulting in systemic toxicity such as cytokine release syndrome and neurotoxicity. E Tumor heterogeneity, immune editing and reduced antigen presentation prevent recognition and killing from injected T and NK cells. F Injected monocytes, monocytes derived from injected HSCs and neutrophils are more efficiently recruited to solid tumors than T or NK cells and macrophages. G Macrophages or monocyte-derived macrophages engineered to deliver pro-inflammatory cytokines, can reverse local immunosuppression and promote anti-tumor immune responses including increased recruitment of effector innate and adaptive immune cells